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Insuman (insulin human) – Package leaflet - A10ABCD01

Updated on site: 08-Oct-2017

Medication nameInsuman
ATC CodeA10ABCD01
Substanceinsulin human
ManufacturerSanofi-aventis Deutschland GmbH

Article Contents

Package leaflet: Information for the user

Insuman Rapid 100 IU/ml solution for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Rapid is and what it is used for

2.What you need to know before you use Insuman Rapid

3.How to use Insuman Rapid

4.Possible side effects

5.How to store Insuman Rapid

6.Contents of the pack and other information

1.What Insuman Rapid is and what it is used for

Insuman Rapid contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Rapid is an insulin solution with a rapid onset and short duration of action.

Insuman Rapid is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar. Insuman Rapid may also be used for treating hyperglycaemic coma (coma caused by too much blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar) as well as for controlling blood sugar before, during and after surgery.

2. What you need to know before you use Insuman Rapid

Do not use Insuman Rapid

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Rapid.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Rapid

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia), isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Rapid with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Rapid in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Rapid

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Rapid per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Rapid.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Rapid is injected under the skin 15 to 20 minutes before a meal.

Method of administration

Insuman Rapid is a solution for injection under the skin or, in exceptional circumstances, into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Insulin administration into a vein for example to treat severe hyperglycaemia and ketoacidosis, requires experience and special safety precautions. For these reasons, it must be done in a clinic or a similar setting.

Do not use Insuman Rapid in insulin pumps – special insulin preparations are available for use in such devices. Also do not use it in peristaltic pumps with silicone tubing.

How to handle the vials

Insuman Rapid contains 100 IU insulin per ml. Only injection syringes designed for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Insuman Rapid must only be used if the solution is clear, colourless, with no solid particles visible, and has a water-like consistency.

Do not shake the vial vigorously as this could cause froth to form. Froth can make it difficult for you to measure the correct dose.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Rapid may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw Insuman Rapid into the injection syringe before the other insulin. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Rapid than you should

-If you have injected too much Insuman Rapid, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Rapid

-If you have missed a dose of Insuman Rapid or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Rapid

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Rapid without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Rapid and other insulins.

4.Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store Insuman Rapid

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Rapid next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Rapid contains

-The active substance is insulin human. One ml of Insuman Rapid contains 100 IU (International Units) of the active substance insulin human.

-The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Rapid”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Rapid looks like and contents of the pack

Insuman Rapid is a clear, colourless solution for injection, with no solid particles visible, and of a water-like consistency.

Insuman Rapid is supplied in vials containing 5 ml of solution for injection (equivalent to 500 IU) or 10 ml of solution for injection (equivalent to 1000 IU). Packs of 1 and 5 vials of 5 ml or 10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and

tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Rapid 40 IU/ml solution for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Rapid is and what it is used for

2.What you need to know before you use Insuman Rapid

3.How to use Insuman Rapid

4.Possible side effects

5.How to store Insuman Rapid

6.Contents of the pack and other information

1. What Insuman Rapid is and what it is used for

Insuman Rapid contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Rapid is an insulin solution with a rapid onset and short duration of action.

Insuman Rapid is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar. Insuman Rapid may also be used for treating hyperglycaemic coma (coma caused by too much blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar) as well as for controlling blood sugar before, during and after surgery.

2. What you need to know before you use Insuman Rapid

Do not use Insuman Rapid

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Rapid.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Rapid

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Rapid with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Rapid in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Rapid

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Rapid per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Rapid.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Rapid is injected under the skin 15 to 20 minutes before a meal.

Method of administration

Insuman Rapid is a solution for injection under the skin or, in exceptional circumstances, into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Insulin administration into a vein for example to treat severe hyperglycaemia and ketoacidosis, requires experience and special safety precautions. For these reasons, it must be done in a clinic or a similar setting.

Do not use Insuman Rapid in insulin pumps – special insulin preparations are available for use in such devices. Also do not use it in peristaltic pumps with silicone tubing.

How to handle the vials

Insuman Rapid contains 40 IU insulin per ml. Only injection syringes designed for this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Insuman Rapid must only be used if the solution is clear, colourless, with no solid particles visible, and has a water-like consistency.

Do not shake the vial vigorously as this could cause froth to form. Froth can make it difficult for you to measure the correct dose.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Rapid may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw Insuman Rapid into the injection syringe before the other insulin. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Rapid than you should

-If you have injected too much Insuman Rapid, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Rapid

-If you have missed a dose of Insuman Rapid or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Rapid

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Rapid without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Rapid and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not know (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not know

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Rapid

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insuman Rapid next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Rapid contains

-The active substance is insulin human. One ml of Insuman Rapid contains 40 IU (International Units) of the active substance insulin human.

-The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Rapid”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Rapid looks like and contents of the pack

Insuman Rapid is a clear, colourless solution for injection, with no solid particles visible, and of a water-like consistency.

Insuman Rapid is supplied in vials containing 10 ml solution (400 IU). Packs of 1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep

breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Rapid 100 IU/ml solution for injection in a cartridge

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you. The instructions for using the insulin pen are provided with your insulin pen. Refer to them before using your medicine.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Rapid is and what it is used for

2.What you need to know before you use Insuman Rapid

3.How to use Insuman Rapid

4.Possible side effects

5.How to store Insuman Rapid

6.Contents of the pack and other information

1. What Insuman Rapid is and what it is used for

Insuman Rapid contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Rapid is an insulin solution with a rapid onset and short duration of action.

Insuman Rapid is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar. Insuman Rapid may also be used for treating hyperglycaemic coma (coma caused by too much blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar) as well as for controlling blood sugar before, during and after surgery.

2. What you need to know before you use Insuman Rapid

Do not use Insuman Rapid

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Rapid.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Rapid

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions orhigh blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Rapid with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Rapid in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Rapid

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Rapid per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Rapid.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Rapid is injected under the skin 15 to 20 minutes before a meal.

Method of administration

Insuman Rapid is a solution for injection under the skin or, in exceptional circumstances, into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Insulin administration into a vein for example to treat severe hyperglycaemia and ketoacidosis, requires experience and special safety precautions. For these reasons, it must be done in a clinic or a similar setting.

Do not use Insuman Rapid in insulin pumps - special insulin preparations are available for use in such devices. Also do not use it in peristaltic pumps with silicone tubing.

How to handle the cartridges

To ensure you get the accurate dose, the Insuman Rapid cartridges are to be used only with the following pens:

-JuniorSTAR which delivers doses in steps of 0.5 units

-OptiPen, ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO which deliver doses in steps of 1 unit.

Not all of these pens may be marketed in your country.

The pen should be used as recommended in the information provided by the device manufacturer. The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, attaching the injection needle, and administering the insulin injection.

Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen.

Look at the cartridge before you use it. Only use it if the solution is clear, colourless, with no solid particles visible, and has a water-like consistency.

Special care before injection

Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

-Do not re-fill and re-use empty cartridges.

-Do not add any other insulin to the cartridge.

-Do not mix Insuman Rapid with any other medicines.

Problems with the pen?

Refer to the manufacturer’s instructions for using the pen.

If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be discarded, and a new insulin pen has to be used.

If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. Therefore, keep injection syringes and needles as well. However, use only those injection syringes which are designed for an insulin concentration of 100 IU (International Units) per ml.

If you use more Insuman Rapid than you should

-If you have injected too much Insuman Rapid, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Rapid

-If you have missed a dose of Insuman Rapid or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Rapid

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Rapid without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Rapid and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Rapid

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the cartridge after “EXP”. The expiry date refers to the last day of that month.

Unopened cartridges

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Rapid next to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect from light.

In-use cartridges

Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the cartridge after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Rapid contains

-The active substance is insulin human. One ml of Insuman Rapid contains 100 IU (International Units) of the active substance insulin human.

-The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Rapid”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Rapid looks like and contents of the pack

Insuman Rapid is a clear, colourless solution for injection, with no solid particles visible, and of a water-like consistency.

Insuman Rapid is supplied in cartridges containing 3 ml solution (300 IU). Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Rapid Solostar 100 IU/ml solution for injection in a pre-filled pen

Insulin human

Read all of this leaflet carefully including the Instructions for Use of Insuman Rapid SoloStar, pre-filled pen, before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Rapid is and what it is used for

2.What you need to know before you use Insuman Rapid

3.How to use Insuman Rapid

4.Possible side effects

5.How to store Insuman Rapid

6.Contents of the pack and other information

1. What Insuman Rapid is and what it is used for

Insuman Rapid contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Rapid is an insulin solution with a rapid onset and short duration of action. It comes in cartridges sealed in disposable pen injectors, SoloStar.

Insuman Rapid is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Rapid

Do not use Insuman Rapid

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Rapid.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise), injection technique as discussed with your doctor.

If you are allergic to this medicine or to animal insulins talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Rapid

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Rapid with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast feeding think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your babyHowever, there is no experience with the use of Insuman Rapid in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Rapid

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Rapid

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Rapid per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Rapid.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Rapid is injected under the skin 15 to 20 minutes before a meal.

Method of administration

Insuman Rapid is a solution for injection under the skin.

SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

How to handle SoloStar

SoloStar is a pre-filled disposable pen containing insulin human.

Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must use the pen as described in these Instructions for Use.

A new injection needle must be attached before each use. Only use needles that have been approved for use with SoloStar.

A safety test must be performed before each injection.

Look at the cartridge before you use the pen. Do not use Insuman Rapid if you notice particles in it. Only use Insuman Rapid if the solution is clear, colourless and waterlike.

Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.

To prevent the possible transmission of disease, each pen must be used by one patient only.

Special care before injection

Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

Do not mix insulin with any other medicines. Insuman Rapid Solostar pre-filled pen, is not designed to allow any other insulin to be mixed in the cartridge.

Empty pens must not be re-filled and must be properly discarded.

Do not use SoloStar if it is damaged or not working properly, it has to be discarded and a new SoloStar has to be used.

If you use more Insuman Rapid than you should

-If you have injected too much Insuman Rapid, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Rapid

-If you have missed a dose of Insuman Rapid or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Rapid

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Rapid without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Rapid and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Rapid.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen after “EXP”. The expiry date refers to the last day of that month.

Not in-use pens

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from light.

In-use pens

Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Rapid contains

-The active substance is insulin human. One ml of Insuman Rapid contains 100 IU (International Units) of the active substance insulin human.

-The other ingredients are: metacresol, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Rapid”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Rapid looks like and contents of the pack

Insuman Rapid is a clear, colourless solution for injection, with no solid particles visible, and of a water-like consistency.

Insuman Rapid is supplied in pre-filled pens, SoloStar, containing 3 ml solution (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A. Tel: +34 93 485 94 00

sanofi-aventis Sp. z o.o.

 

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Rapid").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Rapid").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Insuman Rapid SoloStar solution for injection in a pre-filled pen. Instructions for Use.

SoloStar is a pre-filled pen for the injection of insulin. Your doctor has decided that SoloStar is appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or nurse about proper injection technique before using SoloStar.

Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or follow all the instructions completely on your own, you must use SoloStar only if you have help from a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the dosage selector to the right as shown in the illustrations below.

Follow these instructions completely each time you use SoloStar to ensure that you get an accurate dose. If you do not follow these instructions completely, you may get too much or too little insulin, which may affect your blood glucose.

You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Keep this leaflet for future reference.

If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or call the local sanofi-aventis number on the front of this leaflet.

Schematic diagram of the pen

Important information for use of SoloStar:

Always attach a new needle before each use. Only use needles that have been approved for use with SoloStar.

Do not select a dose and/or press the injection button without a needle attached.

Always perform the safety test before each injection (see Step 3).

This pen is only for your use. Do not share it with anyone else.

If your injection is given by another person, special caution must be taken by this person to avoid accidental needle injury and transmission of infection.

Never use SoloStar if it is damaged or if you are not sure that it is working properly.

Always have a spare SoloStar in case your SoloStar is lost or damaged.

Step 1. Check the insulin

A. Check the label on your SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a colour on the injection button. The injection button colour will vary based on the formulation of Insuman insulin used. The pictures below are for illustrative purposes only.

B. Take off the pen cap.

C. Check the appearance of your insulin.

If you are using clear insulin (Insuman Rapid), do not use this pen if the insulin is cloudy, coloured or has particles.

Step 2. Attach the needle

Always use a new sterile needle for each injection. This helps prevent contamination, and potential needle blocks.

Before use of the needle, carefully read the “Instructions for Use” accompanying the needles.

Please note: The needles shown are for illustrative purposes only.

A. Remove the protective seal from a new needle.

B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, depending on the needle type).

.

If the needle is not kept straight while you attach it, it can damage the rubber seal and cause leakage, or break the needle.

Step 3. Perform a safety test

Always perform the safety test before each injection. This ensures that you get an accurate dose by:

ensuring that pen and needle work properly

removing air bubbles

A. Select a dose of 2 units by turning the dosage selector.

B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and discard it.

C. Hold the pen with the needle pointing upwards.

D. Tap the insulin reservoir so that any air bubbles rise up towards the needle.

E. Press the injection button all the way in. Check if insulin comes out of the needle tip.

You may have to perform the safety test several times before insulin is seen.

If no insulin comes out, check for air bubbles and repeat the safety test two more times to remove them.

If still no insulin comes out, the needle may be blocked. Change the needle and try again.

If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use this SoloStar.

Step 4. Select the dose

You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you need a dose greater than 80 units, you should give it as two or more injections.

A. Check that the dose window shows “0” following the safety test.

B. Select your required dose (in the

example below, the selected dose is 30 units). If you turn past your dose, you can turn back down.

Do not push the injection button while turning, as insulin will come out.

You cannot turn the dosage selector past the number of units left in the pen. Do not force the dosage selector to turn. In this case, either you can inject what is remaining in the pen and complete your dose with a new SoloStar or use a new SoloStar for your full dose.

Step 5. Inject the dose

A. Use the injection method as instructed by your doctor, pharmacist or nurse.

B. Insert the needle into the skin.

C. Deliver the dose by pressing the injection button in all the way. The number in the dose window will return to “0” as you inject.

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the needle from the skin. This ensures that the full dose will be delivered.

The pen plunger moves with each dose. The plunger will reach the end of the cartridge when the total of 300 units of insulin has been used.

Step 6. Remove and discard the needle

Always remove the needle after each injection and store SoloStar without a needle attached. This helps prevent:

Contamination and/or infection

Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing.

A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never replace the inner needle cap.

If your injection is given by another person, or if you are giving an injection to another person, special caution must be taken by this person when removing and disposing of the needle. Follow recommended safety measures for removal and disposal of needles (e.g. contact your doctor, pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of infectious diseases.

B. Dispose of the needle safely.

C. Always put the pen cap back on the pen, then store the pen until your next injection.

Storage instructions

Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar.

If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up to room temperature. Cold insulin is more painful to inject.

Discard your used SoloStar as required by your local authorities.

Maintenance

Protect your SoloStar from dust and dirt.

You can clean the outside of your SoloStar by wiping it with a damp cloth.

Do not soak, wash or lubricate the pen as this may damage it.

Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid situations where SoloStar might be damaged. If you are concerned that your SoloStar may be damaged, use a new one.

Package leaflet: Information for the user

Insuman Basal 100 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Basal is and what it is used for

2.What you need to know before you use Insuman Basal

3.How to use Insuman Basal

4.Possible side effects

5.How to store Insuman Basal

6.Contents of the pack and other information

1.What Insuman Basal is and what it is used for.

Insuman Basal contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Basal is an insulin preparation with a gradual onset and long duration of action. The insulin is present as tiny crystals of insulin protamine.

Insuman Basal is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Basal

Do not use Insuman Basal

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Basal

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Basal

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Basal with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Basal in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Basal

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Basal per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Basal.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Basal is injected under the skin 45 to 60 minutes before a meal.

Method of administration

Basal is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Basal into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for use in such devices

How to handle the vials

Insuman Basal contains 100 IU insulin per ml. Only injection syringes designed for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Basal may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparation. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Basal. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Basal than you should

-If you have injected too much Insuman Basal, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Basal

-If you have missed a dose of Insuman Basal or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Basal

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Basal without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Basal and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antobodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store Insuman Basal

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insuman Basal next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Basal contains

-The active substance is insulin human. One ml of Insuman Basal contains 100 IU (International Units) of the active substance insulin human.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Basal”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Basal looks like and contents of the pack

After mixing, Insuman Basal is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Basal is supplied in vials containing 5 ml of suspension for injection (equivalent to 500 IU) or 10 ml of suspension for injection (equivalent to 1000 IU). Packs of 1 and 5 vials of 5 ml or 10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A. Tel: +34 93 485 94 00

sanofi-aventis Sp. z o.o.

 

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Basal").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Basal 40 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Basal is and what it is used for

2.What you need to know before you use Insuman Basal

3.How to use Insuman Basal

4.Possible side effects

5.How to store Insuman Basal

6.Contents of the pack and other information

1. What Insuman Basal is and what it is used for

Insuman Basal contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Basal is an insulin preparation with a gradual onset and long duration of action. The insulin is present as tiny crystals of insulin protamine.

Insuman Basal is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Basal

Do not use Insuman Basal

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Basal.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Basal

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Basal with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Basal in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Basal

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Basal per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Basal.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Basal is injected under the skin 45 to 60 minutes before a meal.

Method of administration

Insuman Basal is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Basal into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for use in such devices.

How to handle the vials

Insuman Basal contains 40 IU insulin per ml. Only injection syringes designed for this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Basal may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Basal. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Basal than you should

-If you have injected too much Insuman Basal, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Basal

-If you have missed a dose of Insuman Basal or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Basal

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Basal without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Basal and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Basal

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Basal next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Basal contains

-The active substance is insulin human. One ml of Insuman Basal contains 40 IU (International Units) of the active substance insulin human.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Basal”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Basal looks like and contents of the pack

After mixing, Insuman Basal is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Basal is supplied in vials containing 10 ml suspension (400 IU). Packs of 1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A. Tel: +34 93 485 94 00

sanofi-aventis Sp. z o.o.

 

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Basal").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Basal 100 IU/ml suspension for injection in a cartridge

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you. The instructions for using the insulin pen are provided with your insulin pen. Refer to them before using your medicine.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Basal is and what it is used for

2.What you need to know before you use Insuman Basal

3.How to use Insuman Basal

4.Possible side effects

5.How to store Insuman Basal

6.Contents of the pack and other information

1.What Insuman Basal is and what is it used for

Insuman Basal contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Basal is an insulin preparation with a gradual onset and long duration of action. The insulin is present as tiny crystals of insulin protamine.

Insuman Basal is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Basal

Do not use Insuman Basal

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Basal.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Basal

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Basal with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Basal in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Basal

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Basal per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Basal.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Basal is injected under the skin 45 to 60 minutes before a meal.

Method of administration

Insuman Basal is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Basal into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for use in such devices.

How to handle the cartridges

To ensure you get the accurate dose, the Insuman Basal cartridges are to be used only with the following pens:

-JuniorSTAR which delivers doses in steps of 0.5 units

-OptiPen, ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO which deliver doses in steps of 1 unit.

Not all of these pens may be marketed in your country.

The pen should be used as recommended in the information provided by the device manufacturer. The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, attaching the injection needle, and administering the insulin injection.

Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must then be used.

Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

-Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.Do not re-fill and re-use empty cartridges.

-Do not add any other insulin to the cartridge.

-Do not mix insulin with any other medicines.

Problems with the pen?

Refer to the manufacturer’s instructions for using the pen.

If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be discarded, and a new insulin pen has to be used.

If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. Therefore, keep injection syringes and needles as well. However, use only those injection syringes which are designed for an insulin concentration of 100 IU (International Units) per ml.

If you use more Insuman Basal than you should

-If you have injected too much Insuman Basal, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Basal

-If you have missed a dose of Insuman Basal or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Basal

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Basal without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Basal and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Basal

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the cartridge after “EXP”. The expiry date refers to the last day of that month.

Unopened cartridges

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insuman Basal next to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect from light.

In-use cartridges

Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the cartridge after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Basal contains

-The active substance is insulin human. One ml of Insuman Basal contains 100 IU (International Units) of the active substance insulin human.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Basal”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Basal looks like and contents of the pack

After mixing, Insuman Basal is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Basal is supplied in cartridges containing 3 ml suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A. Tel: +34 93 485 94 00

sanofi-aventis Sp. z o.o.

 

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Basal").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Basal SoloStar 100 IU/ml suspension for injection in a pre-filled pen

Insulin human

Read all of this leaflet carefully including the Instructions for Use of Insuman Basal SoloStar, pre-filled pen, before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Basal is and what it is used for

2.What you need to know before you use Insuman Basal

3.How to use Insuman Basal

4.Possible side effects

5.How to store Insuman Basal

6.Contents of the pack and other information

1. What Insuman Basal is and what it is used for

Insuman Basal contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Basal is an insulin preparation with a gradual onset and long duration of action. The insulin is present as tiny crystals of insulin protamine. It comes in cartridges sealed in disposable pen injectors, SoloStar.

Insuman Basal is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Basal

Do not use Insuman Basal

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Basal.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise), injection technique as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Basal

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Basal with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Basal in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Basal

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Basal

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Basal per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Basal.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Basal is injected under the skin 45 to 60 minutes before a meal.

Method of administration

Insuman Basal is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Basal into a vein (blood vessel).

SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

How to handle SoloStar

SoloStar is a pre-filled disposable pen containing insulin human.

Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must use the pen as described in these Instructions for Use.

A new injection needle must be attached before each use. Only use needles that have been approved for use with SoloStar.

A safety test must be performed before each injection.

Mix the insulin well and check it before first use. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing must then be used.

Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.

To prevent the possible transmission of disease, each pen must be used by one patient only.

Special care before injection

Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

Do not mix insulin with any other medicines. Insuman Basal SoloStar, pre-filled pen, is not designed to allow any other insulin to be mixed in the cartridge.

Empty pens must not be re-filled and must be properly discarded.

Do not use SoloStar if it is damaged or not working properly, it has to be discarded and a new SoloStar has to be used.

If you use more Insuman Basal than you should

-If you have injected too much Insuman Basal, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Basal

-If you have missed a dose of Insuman Basal or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Basal

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Basal without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Basal and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

• The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

• Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Basal

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen after “EXP”. The expiry date refers to the last day of that month.

Not in-use pens

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from light.

In-use pens

Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Basal contains

-The active substance is insulin human. One ml of Insuman Basal contains 100 IU (International Units) of the active substance insulin human.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Basal), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Basal looks like and contents of the pack

After mixing, Insuman Basal is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Basal is supplied in pre-filled pens, SoloStar, containing 3 ml suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A. Tel: +34 93 485 94 00

sanofi-aventis Sp. z o.o.

 

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Basal").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Basal").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Insuman Basal SoloStar suspension for injection in a pre-filled pen. Instructions for Use.

SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or nurse about proper injection technique before using SoloStar.

Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or follow all the instructions completely on your own, you must use SoloStar only if you have help from a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the dosage selector to the right as shown in the illustrations below.

Follow these instructions completely each time you use SoloStar to ensure that you get an accurate dose. If you do not follow these instructions completely, you may get too much or too little insulin, which may affect your blood glucose.

You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Keep this leaflet for future reference.

If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or call the local sanofi-aventis number on the front of this leaflet.

Schematic diagram of the pen

Important information for use of SoloStar:

Always attach a new needle before each use. Only use needles that have been approved for use with SoloStar.

Do not select a dose and/or press the injection button without a needle attached.

Always perform the safety test before each injection (see Step 3).

This pen is only for your use. Do not share it with anyone else.

If your injection is given by another person, special caution must be taken by this person to avoid accidental needle injury and transmission of infection.

Never use SoloStar if it is damaged or if you are not sure that it is working properly.

Always have a spare SoloStar in case your SoloStar is lost or damaged.

Step 1. Check the insulin

A. Check the label on your SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a colour on the injection button. The injection button colour will vary based on the formulation of Insuman insulin used. The pictures below are for illustrative purposes only.

B. Take off the pen cap.

C. Check the appearance of your insulin.

If you are using a suspension insulin (Insuman Basal or Insuman mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn the pen gently to avoid foaming in the cartridge.

After mixing check the appearance of your insulin. Insulin suspensions must have an evenly milky-white appearance.

Step 2. Attach the needle

Always use a new sterile needle for each injection. This helps prevent contamination, and potential needle blocks.

Before use of the needle, carefully read the “Instructions for Use” accompanying the needles.

Please note: The needles shown are for illustrative purposes only.

A. Remove the protective seal from a new needle.

B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, depending on the needle type).

.

If the needle is not kept straight while you attach it, it can damage the rubber seal and cause leakage, or break the needle.

Step 3. Perform a safety test

Always perform the safety test before each injection. This ensures that you get an accurate dose by:

ensuring that pen and needle work properly

removing air bubbles

A. Select a dose of 2 units by turning the dosage selector.

B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and discard it.

C. Hold the pen with the needle pointing upwards.

D. Tap the insulin reservoir so that any air bubbles rise up towards the needle.

E. Press the injection button all the way in. Check if insulin comes out of the needle tip.

You may have to perform the safety test several times before insulin is seen.

If no insulin comes out, check for air bubbles and repeat the safety test two more times to remove them.

If still no insulin comes out, the needle may be blocked. Change the needle and try again.

If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use this SoloStar.

Step 4. Select the dose

You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you need a dose greater than 80 units, you should give it as two or more injections.

A. Check that the dose window shows “0” following the safety test.

B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past your dose, you can turn back down.

Do not push the injection button while turning, as insulin will come out.

You cannot turn the dosage selector past the number of units left in the pen. Do not force the dosage selector to turn. In this case, either you can inject what is remaining in the pen and complete your dose with a new SoloStar or use a new SoloStar for your full dose.

Step 5. Inject the dose

A. Use the injection method as instructed by your doctor, pharmacist or nurse.

B. Insert the needle into the skin.

C. Deliver the dose by pressing the injection button in all the way. The number in the dose window will return to “0” as you inject.

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the needle from the skin. This ensures that the full dose will be delivered.

The pen plunger moves with each dose. The plunger will reach the end of the cartridge when the total of 300 units of insulin has been used.

Step 6. Remove and discard the needle

Always remove the needle after each injection and store SoloStar without a needle attached. This helps prevent:

Contamination and/or infection

Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing.

A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never replace the inner needle cap.

If your injection is given by another person, or if you are giving an injection to another person, special caution must be taken by this person when removing and disposing of the needle. Follow recommended safety measures for removal and disposal of needles (e.g. contact your doctor, pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of infectious diseases.

B. Dispose of the needle safely.

C. Always put the pen cap back on the pen, then store the pen until your next injection.

Storage instructions

Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar.

If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up at room temperature. Cold insulin is more painful to inject.

Discard your used SoloStar as required by your local authorities.

Maintenance

Protect your SoloStar from dust and dirt.

You can clean the outside of your SoloStar by wiping it with a damp cloth.

Do not soak, wash or lubricate the pen as this may damage it.

Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid situations where SoloStar might be damaged. If you are concerned that your SoloStar may be damaged, use a new one.

Package leaflet:Information for the user

Insuman Comb 15 100 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 15 is and what it is used for

2.What you need to know before you use Insuman Comb 15

3.How to use Insuman Comb 15

4.Possible side effects

5.How to store Insuman Comb 15

6.Contents of the pack and other information

1.What Insuman Comb 15 is and what it is used for

Insuman Comb 15 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 15 is an insulin preparation with a gradual onset and long duration of action.

Insuman Comb 15 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 15

Do not use Insuman Comb 15

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 15.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb°15

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 15 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 15 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 15

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 15

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 15 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 15.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 15 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 15 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 15 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for use in such devices.

How to handle the vials

Insuman Comb 15 contains 100 IU insulin per ml. Only injection syringes designed for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Comb 15 may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Comb 15. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 15 than you should

-If you have injected too much Insuman Comb 15, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 15

-If you have missed a dose of Insuman Comb 15 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 15

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 15 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 15 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reporting with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body),

severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reporting with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store Insuman Comb 15

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insuman Comb 15 next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 15 contains

-The active substance is insulin human. One ml of Insuman Comb 15 contains 100 IU (International Units) of the active substance insulin human. 15% of the insulin is dissolved in water; the other 85% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb°15), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 15 looks like and contents of the pack

After mixing, Insuman Comb 15 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 15 is supplied in vials containing 5 ml suspension (500 IU). Packs of 1 and 5 vials of 5 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A. Tel: +34 93 485 94 00

sanofi-aventis Sp. z o.o.

 

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb°15").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb°15").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb°15").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 15 100 IU/ml suspension for injection in a cartridge

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you. The instructions for using the insulin pen are provided with your insulin pen. Refer to them before using your medicine.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 15 is and what it is used for

2.What you need to know before you use Insuman Comb 15

3.How to use Insuman Comb 15

4.Possible side effects

5.How to store Insuman Comb 15

6.Contents of the pack and other information

1. What Insuman Comb 15 is and what it is used for

Insuman Comb 15 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 15 is an insulin preparation with a gradual onset and long duration of action.

Insuman Comb 15 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 15

Do not use Insuman Comb 15

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 15.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 15

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 15 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 15 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 15

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 15

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 15 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 15.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 15 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 15 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 15 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for use in such devices.

How to handle the cartridges

To ensure you get the accurate dose, the Insuman Comb 15 cartridges are to be used only with the following pens:

-JuniorSTAR which delivers doses in steps of 0.5 units

-OptiPen, ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO which deliver doses in steps of 1 unit.

Not all of these pens may be marketed in your country.

The pen should be used as recommended in the information provided by the device manufacturer. The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, attaching the injection needle, and administering the insulin injection.

Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must then be used.

Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

-Do not re-fill and re-use empty cartridges.

-Do not add any other insulin to the cartridge.

-Do not mix insulin with any other medicines.

Problems with the pen?

Refer to the manufacturer’s instructions for using the pen.

If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be discarded, and a new insulin pen has to be used.

If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. Therefore, keep injection syringes and needles as well. However, use only those injection syringes which are designed for an insulin concentration of 100 IU (International Units) per ml.

If you use more Insuman Comb 15 than you should

-If you have injected too much Insuman Comb 15, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 15

-If you have missed a dose of Insuman Comb 15 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 15

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 15 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 15 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 15

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the cartridge after “EXP”. The expiry date refers to the last day of that month.

Unopened cartridges

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insuman Comb 15 next to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect from light.

In-use cartridges

Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the cartridge after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 15 contains

-The active substance is insulin human. One ml of Insuman Comb 15 contains 100 IU (International Units) of the active substance insulin human. 15% of the insulin is dissolved in water; the other 85% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 15”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 15 looks like and contents of the pack

After mixing, Insuman Comb 15 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 15 is supplied in cartridges containing 3 ml suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 15").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 15").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 15").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage.Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 15 SoloStar 100 IU/ml suspension for injection in a pre-filled pen

Insulin human

Read all of this leaflet carefully including the Instructions for Use of Insuman Comb 15 SoloStar, pre-filled pen, before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 15 is and what it is used for

2.What you need to know before you use Insuman Comb 15

3.How to use Insuman Comb 15

4.Possible side effects

5.How to store Insuman Comb 15

6.Contents of the pack and other information

1. What Insuman Comb 15 is and what it is used for

Insuman Comb 15 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 15 is an insulin preparation with a gradual onset and long duration of action. It comes in cartridges sealed in disposable pen injectors, SoloStar.

Insuman Comb 15 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 15

Do not use Insuman Comb 15

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 15.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise), injection technique as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 15

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 15 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 15 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 15

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 15

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 15 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 15.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 15 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 15 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 15 into a vein (blood vessel).

SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

How to handle SoloStar

SoloStar is a pre-filled disposable pen containing insulin human.

Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must use the pen as described in these Instructions for Use.

A new injection needle must be attached before each use. Only use needles that have been approved for use with SoloStar.

A safety test must be performed before each injection.

Mix the insulin well and check it before first use. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing must then be used.

Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.

To prevent the possible transmission of disease, each pen must be used by one patient only.

Special care before injection

Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

Do not mix insulin with any other medicines. Insuman Comb 15 SoloStar, pre-filled pen, SoloStar, is not designed to allow any other insulin to be mixed in the cartridge.

Empty pens must not be re-filled and must be properly discarded.

Do not use SoloStar if it is damaged or not working properly, it has to be discarded and a new SoloStar has to be used.

If you use more Insuman Comb 15 than you should

-If you have injected too much Insuman Comb 15, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 15

-If you have missed a dose of Insuman Comb 15 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 15

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 15 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 15 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body),

severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effectsreported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 15

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen after “EXP”. The expiry date refers to the last day of that month.

Not in-use pens

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from light.

In-use pens

Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 15 contains

-The active substance is insulin human. One ml of Insuman Comb 15 contains 100 IU (International Units) of the active substance insulin human. 15% of the insulin is dissolved in water; the other 85% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 15”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 15 looks like and contents of the pack

After mixing, Insuman Comb 15 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 15 is supplied in pre-filled pens, SoloStar, containing 3 ml suspension, (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

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Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

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Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb°15").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 15").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb°15").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Insuman Comb 15 SoloStar suspension for injection in a pre-filled pen. Instructions for Use.

SoloStar is a pre-filled pen for the injection of insulin. Your doctor has decided that SoloStar is appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or nurse about proper injection technique before using SoloStar.

Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or follow all the instructions completely on your own, you must use SoloStar only if you have help from a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the dosage selector to the right as shown in the illustrations below.

Follow these instructions completely each time you use SoloStar to ensure that you get an accurate dose. If you do not follow these instructions completely, you may get too much or too little insulin, which may affect your blood glucose.

You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Keep this leaflet for future reference.

If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or call the local sanofi-aventis number on the front of this leaflet.

Schematic diagram of the pen

Important information for use of SoloStar:

Always attach a new needle before each use. Only use needles that have been approved for use with SoloStar.

Do not select a dose and/or press the injection button without a needle attached.

Always perform the safety test before each injection (see Step 3).

This pen is only for your use. Do not share it with anyone else.

If your injection is given by another person, special caution must be taken by this person to avoid accidental needle injury and transmission of infection.

Never use SoloStar if it is damaged or if you are not sure that it is working properly.

Always have a spare SoloStar in case your SoloStar is lost or damaged.

Step 1. Check the insulin

A. Check the label on your SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a colour on the injection button. The injection button colour will vary based on the formulation of Insuman insulin used. The pictures below are for illustrative purposes only.

B. Take off the pen cap.

C. Check the appearance of your insulin.

If you are using a suspension insulin (Insuman Basal or Insuman mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn the pen gently to avoid foaming in the cartridge.

After mixing check the appearance of your insulin. Insulin suspensions must have an evenly milky-white appearance.

Step 2. Attach the needle

Always use a new sterile needle for each injection. This helps prevent contamination, and potential needle blocks.

Before use of the needle, carefully read the “Instructions for Use” accompanying the needles.

Please note: The needles shown are for illustrative purposes only.

A. Remove the protective seal from a new needle.

B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, depending on the needle type).

.

If the needle is not kept straight while you attach it, it can damage the rubber seal and cause leakage, or break the needle.

Step 3. Perform a safety test

Always perform the safety test before each injection. This ensures that you get an accurate dose by:

ensuring that pen and needle work properly

removing air bubbles

A. Select a dose of 2 units by turning the dosage selector.

B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and discard it.

C. Hold the pen with the needle pointing upwards.

D. Tap the insulin reservoir so that any air bubbles rise up towards the needle.

E. Press the injection button all the way in. Check if insulin comes out of the needle tip.

You may have to perform the safety test several times before insulin is seen.

If no insulin comes out, check for air bubbles and repeat the safety test two more times to remove them.

If still no insulin comes out, the needle may be blocked. Change the needle and try again.

If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use this SoloStar.

Step 4. Select the dose

You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you need a dose greater than 80 units, you should give it as two or more injections.

A. Check that the dose window shows “0” following the safety test.

B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past your dose, you can turn back down.

Do not push the injection button while turning, as insulin will come out.

You cannot turn the dosage selector past the number of units left in the pen. Do not force the dosage selector to turn. In this case, either you can inject what is remaining in the pen and complete your dose with a new SoloStar or use a new SoloStar for your full dose.

Step 5. Inject the dose

A. Use the injection method as instructed by your doctor, pharmacist or nurse.

B. Insert the needle into the skin.

C. Deliver the dose by pressing the injection button in all the way. The number in the dose window will return to “0” as you inject.

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the needle from the skin. This ensures that the full dose will be delivered.

The pen plunger moves with each dose. The plunger will reach the end of the cartridge when the total of 300 units of insulin has been used.

Step 6. Remove and discard the needle

Always remove the needle after each injection and store SoloStar without a needle attached. This helps prevent:

Contamination and/or infection

Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing.

A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never replace the inner needle cap.

If your injection is given by another person, or if you are giving an injection to another person, special caution must be taken by this person when removing and disposing of the needle. Follow recommended safety measures for removal and disposal of needles (e.g. contact your doctor, pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of infectious diseases.

B. Dispose of the needle safely.

C. Always put the pen cap back on the pen, then store the pen until your next injection.

Storage instructions

Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar.

If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up at room temperature. Cold insulin is more painful to inject.

Discard your used SoloStar as required by your local authorities.

Maintenance

Protect your SoloStar from dust and dirt.

You can clean the outside of your SoloStar by wiping it with a damp cloth.

Do not soak, wash or lubricate the pen as this may damage it.

Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid situations where SoloStar might be damaged. If you are concerned that your SoloStar may be damaged, use a new one.

Package leaflet Information for the user

Insuman Comb 25 100 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 25 is and what it is used for

2.What you need to know before you use Insuman Comb 25

3.How to use Insuman Comb 25

4.Possible side effects

5.How to store Insuman Comb 25

6.Contents of the pack and other information

1.What Insuman Comb 25 is and what it is used for

Insuman Comb 25 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 25 is an insulin preparation with a gradual onset and long duration of action.

Insuman Comb 25 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 25

Do not use Insuman Comb 25

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 25.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 25

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 25 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 25 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 25

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb°25

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 25 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 25.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 25 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 25 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 25 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for use in such devices.

How to handle the vials

Insuman Comb 25 contains 100 IU insulin per ml. Only injection syringes designed for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Comb 25 may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Comb 25. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 25 than you should

-If you have injected too much Insuman Comb 25, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 25

-If you have missed a dose of Insuman Comb 25 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 25

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 25 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 25 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store Insuman Comb 25

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Comb 25 next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 25 contains

-The active substance is insulin human. One ml of Insuman Comb 25 contains 100 IU (International Units) of the active substance insulin human. 25% of the insulin is dissolved in water; the other 75% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 25”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 25 looks like and contents of the pack

After mixing, Insuman Comb 25 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 25 is supplied in vials containing 5 ml suspension (500 IU). Packs of 1 and 5 vials of 5 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 25 40 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 25 is and what it is used for

2.What you need to know before you use Insuman Comb 25

3.How to use Insuman Comb 25

4.Possible side effects

5.How to store Insuman Comb 25

6.Contents of the pack and other information

1. What Insuman Comb 25 is and what it is used for

Insuman Comb 25 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 25 is an insulin preparation with a gradual onset and long duration of action.

Insuman Comb 25 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 25

Do not use Insuman Comb 25

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 25.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 25

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 25 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 25 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 25

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 25

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 25 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 25.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 25 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 25 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 25 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for use in such devices.

How to handle the vials

Insuman Comb 25 contains 40 IU insulin per ml. Only injection syringes designed for this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Comb 25 may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Comb 25. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 25 than you should

-If you have injected too much Insuman Comb 25, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 25

-If you have missed a dose of Insuman Comb 25 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 25

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 25 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 25 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body),

severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 25

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insuman Comb 25 next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 25 contains

-The active substance is insulin human. One ml of Insuman Comb 25 contains 40 IU (International Units) of the active substance insulin human. 25% of the insulin is dissolved in water; the other 75% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 25”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 25 looks like and contents of the pack

After mixing, Insuman Comb 25 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 25 is supplied in vials containing 10 ml suspension (400 IU). Packs of 1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 25 100 IU/ml suspension for injection in a cartridge

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you. The instructions for using the insulin pen are provided with your insulin pen. Refer to them before using your medicine.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 25 is and what it is used for

2.What you need to know before you use Insuman Comb 25

3.How to use Insuman Comb 25

4.Possible side effects

5.How to store Insuman Comb 25

6.Contents of the pack and other information

1. What Insuman Comb 25 is and what it is used for

Insuman Comb 25 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 25 is an insulin preparation with a gradual onset and long duration of action.

Insuman Comb 25 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 25

Do not use Insuman Comb 25

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 25.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 25

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 25 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 25 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 25

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 25

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 25 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 25.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 25 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 25 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 25 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for use in such devices.

How to handle the cartridges

To ensure you get the accurate dose, the Insuman Comb 25 cartridges are to be used only with the following pens:

-JuniorSTAR which delivers doses in steps of 0.5 units

-OptiPen, ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO which deliver doses in steps of 1 unit.

Not all of these pens may be marketed in your country.

The pen should be used as recommended in the information provided by the device manufacturer. The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, attaching the injection needle, and administering the insulin injection.

Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must then be used.

Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

-Do not re-fill and re-use empty cartridges.

-Do not add any other insulin to the cartridge.

-Do not mix insulin with any other medicines.

Problems with the pen?

Refer to the manufacturer’s instructions for using the pen.

If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be discarded, and a new insulin pen has to be used.

If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. Therefore, keep injection syringes and needles as well. However, use only those injection syringes which are designed for an insulin concentration of 100 IU (International Units) per ml.

If you use more Insuman Comb 25 than you should

-If you have injected too much Insuman Comb 25, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 25

-If you have missed a dose of Insuman Comb 25 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 25

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 25 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 25 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 25

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the cartridge after “EXP”. The expiry date refers to the last day of that month.

Unopened cartridges

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Comb 25 next to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect from light.

In-use cartridges

Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the cartridge after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 25 contains

-The active substance is insulin human. One ml of Insuman Comb 25 contains 100 IU (International Units) of the active substance insulin human. 25% of the insulin is dissolved in water; the other 75% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 25”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 25 looks like and contents of the pack

After mixing, Insuman Comb 25 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 25 is supplied in cartridge containing 3 ml suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 25 SoloStar 100 IU/ml suspension for injection in a pre-filled pen

Insulin human

Read all of this leaflet carefully including the Instructions for Use of Insuman Comb 25 SoloStar, pre-filled pen, before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 25 is and what it is used for

2.What you need to know before you use Insuman Comb 25

3.How to use Insuman Comb 25

4.Possible side effects

5.How to store Insuman Comb 25

6.Contents of the pack and other information

1. What Insuman Comb 25 is and what it is used for

Insuman Comb 25 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 25 is an insulin preparation with a gradual onset and long duration of action. It comes in cartridges sealed in disposable pen injectors, SoloStar.

Insuman Comb 25 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 25

Do not use Insuman Comb 25

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 25.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise), injection technique as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 25

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 25 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 25 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 25

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 25

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 25 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 25.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 25 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 25 is a fluid (suspension) for injection under the skin

Do NOT inject Insuman Comb 25 into a vein (blood vessel).

SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

How to handle SoloStar

SoloStar is a pre-filled disposable pen containing insulin human.

Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must use the pen as described in these Instructions for Use.

A new injection needle must be attached before each use. Only use needles that have been approved for use with SoloStar.

A safety test must be performed before each injection.

Mix the insulin well and check it before first use. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing must then be used.

Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.

To prevent the possible transmission of disease, each pen must be used by one patient only.

Special care before injection

Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

Do not mix insulin with any other medicines. Insuman Comb 25 SoloStar, pre-filled pen, is not designed to allow any other insulin to be mixed in the cartridge.

Empty pens must not be re-filled and must be properly discarded.

Do not use SoloStar if it is damaged or not working properly, it has to be discarded and a new SoloStar has to be used.

If you use more Insuman Comb 25 than you should

-If you have injected too much Insuman Comb 25, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 25

-If you have missed a dose of Insuman Comb 25 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 25

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 25 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 25 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body),

severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 25

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen after “EXP”. The expiry date refers to the last day of that month.

Not in-use pens

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from light.

In-use pens

Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 25 contains

-The active substance is insulin human. One ml of Insuman Comb 25 contains 100 IU (International Units) of the active substance insulin human. 25% of the insulin is dissolved in water; the other 75% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 25”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 25 looks like and contents of the pack

After mixing, Insuman Comb 25 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 25 is supplied in pre-filled pens, SoloStar, containing 3 ml suspension, (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

Sanofi S.p.A.

Sanofi Oy

Tel: 800 13 12 12 (domande di tipo tecnico)

Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

Sverige

sanofi-aventis Cyprus Ltd.

Sanofi AB

Τηλ: +357 22 871600

Tel: +46 (0)8 634 50 00

Latvija

United Kingdom

sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 25").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Insuman Comb 25 SoloStar suspension for injection in a pre-filled pen. Instructions for Use.

SoloStar is a prefilled pen for the injection of insulin. Your doctor has decided that SoloStar is appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or nurse about proper injection technique before using SoloStar.

Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or follow all the instructions completely on your own, you must use SoloStar only if you have help from a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the dosage selector to the right as shown in the illustrations below.

Follow these instructions completely each time you use SoloStar to ensure that you get an accurate dose. If you do not follow these instructions completely, you may get too much or too little insulin, which may affect your blood glucose.

You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Keep this leaflet for future reference.

If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or call the local sanofi-aventis number on the front of this leaflet.

Schematic diagram of the pen

Important information for use of SoloStar:

Always attach a new needle before each use. Only use needles that have been approved for use with SoloStar.

Do not select a dose and/or press the injection button without a needle attached.

Always perform the safety test before each injection (see Step 3).

This pen is only for your use. Do not share it with anyone else.

If your injection is given by another person, special caution must be taken by this person to avoid accidental needle injury and transmission of infection.

Never use SoloStar if it is damaged or if you are not sure that it is working properly.

Always have a spare SoloStar in case your SoloStar is lost or damaged.

Step 1. Check the insulin

A. Check the label on your SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a colour on the injection button. The injection button colour will vary based on the formulation of Insuman insulin used. The pictures below are for illustrative purposes only.

B. Take off the pen cap.

C. Check the appearance of your insulin.

If you are using a suspension insulin (Insuman Basal or Insuman mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn the pen gently to avoid foaming in the cartridge.

After mixing check the appearance of your insulin. Insulin suspensions must have an evenly milky-white appearance.

Step 2. Attach the needle

Always use a new sterile needle for each injection. This helps prevent contamination, and potential needle blocks.

Before use of the needle, carefully read the “Instructions for Use” accompanying the needles.

Please note: The needles shown are for illustrative purposes only.

A. Remove the protective seal from a new needle.

B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, depending on the needle type).

.

If the needle is not kept straight while you attach it, it can damage the rubber seal and cause leakage, or break the needle.

Step 3. Perform a safety test

Always perform the safety test before each injection. This ensures that you get an accurate dose by:

ensuring that pen and needle work properly

removing air bubbles

A. Select a dose of 2 units by turning the dosage selector.

B. Take off the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and discard it.

C. Hold the pen with the needle pointing upwards.

D. Tap the insulin reservoir so that any air bubbles rise up towards the needle.

E. Press the injection button all the way in. Check if insulin comes out of the needle tip.

You may have to perform the safety test several times before insulin is seen.

If no insulin comes out, check for air bubbles and repeat the safety test two more times to remove them.

If still no insulin comes out, the needle may be blocked. Change the needle and try again.

If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use this SoloStar.

Step 4. Select the dose

You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you need a dose greater than 80 units, you should give it as two or more injections.

A. Check that the dose window shows “0” following the safety test.

B. Select your required dose (in the example below, the selected dose is 30 units). If you turn past your dose, you can turn back down.

Do not push the injection button while turning, as insulin will come out.

You cannot turn the dosage selector past the number of units left in the pen. Do not force the dosage selector to turn. In this case, either you can inject what is remaining in the pen and complete your dose with a new SoloStar or use a new SoloStar for your full dose.

Step 5. Inject the dose

A. Use the injection method as instructed by your doctor, pharmacist or nurse.

B. Insert the needle into the skin.

C. Deliver the dose by pressing the injection button in all the way. The number in the dose window will return to “0” as you inject.

D. Keep the injection button pressed all the way in. Slowly count to 10 before you withdraw the needle from the skin. This ensures that the full dose will be delivered.

The pen plunger moves with each dose. The plunger will reach the end of the cartridge when the total of 300 units of insulin has been used.

Step 6. Remove and discard the needle

Always remove the needle after each injection and store SoloStar without a needle attached. This helps prevent:

Contamination and/or infection

Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing.

A. Put the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never replace the inner needle cap.

If your injection is given by another person, or if you are giving an injection to another person, special caution must be taken by this person when removing and disposing of the needle. Follow recommended safety measures for removal and disposal of needles (e.g. contact your doctor, pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of infectious diseases.

B. Dispose of the needle safely.

C. Always put the pen cap back on the pen, then store the pen until your next injection.

Storage instructions

Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar.

If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up to room temperature. Cold insulin is more painful to inject.

Discard your used SoloStar as required by your local authorities.

Maintenance

Protect your SoloStar from dust and dirt.

You can clean the outside of your SoloStar by wiping it with a damp cloth.

Do not soak, wash or lubricate the pen as this may damage it.

Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid situations where SoloStar might be damaged. If you are concerned that your SoloStar may be damaged, use a new one.

Package leaflet: Information for the user

Insuman Comb 30 100 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 30 is and what it is used for

2.What you need to know before you use Insuman Comb 30

3.How to use Insuman Comb 30

4.Possible side effects

5.How to store Insuman Comb 30

6.Contents of the pack and other information

1.What Insuman Comb 30 is and what it is used for

Insuman Comb 30 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 30 is an insulin preparation with a gradual onset and long duration of action.

Insuman Comb 30 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 30

Do not use Insuman Comb 30

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 30.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 30

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 30 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 30 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 30

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 30

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 30 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 30.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 30 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 30 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 30 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for use in such devices.

How to handle the vials

Insuman Comb 30 contains 100 IU insulin per ml. Only injection syringes designed for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Comb 30 may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Comb 30. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 30 than you should

-If you have injected too much Insuman Comb 30, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 30

-If you have missed a dose of Insuman Comb 30 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 30

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 30 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 30 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store Insuman Comb 30

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Comb 30 next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 30 contains

-The active substance is insulin human. One ml of Insuman Comb 30 contains 100 IU (International Units) of the active substance insulin human. 30% of the insulin is dissolved in water; the other 70% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 30”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 30 looks like and contents of the pack

After mixing, Insuman Comb 30 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 30 is supplied in vials containing 5 ml of suspension for injection (equivalent to

500 IU) or 10 ml of suspension for injection (equivalent to 1000 IU). Packs of 1 and 5 vials of 5 ml or 10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

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sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

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Nederland

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Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

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Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

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sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

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Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

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Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

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Tel: +385 1 600 34 00

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Ireland

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Tel: +386 1 560 48 00

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Tel: +421 2 33 100 100

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Sanofi

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Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 30 100 IU/ml suspension for injection in a cartridge

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you. The instructions for using the insulin pen are provided with your insulin pen. Refer to them before using your medicine.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 30 is and what it is used for

2.What you need to know before you use Insuman Comb 30

3.How to use Insuman Comb 30

4.Possible side effects

5.How to store Insuman Comb 30

6.Contents of the pack and other information

1. What Insuman Comb 30 is and what it is used for

Insuman Comb 30 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 30 is an insulin preparation with a gradual onset and long duration of action.

Insuman Comb 30 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 30

Do not use Insuman Comb 30

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 30.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 30

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 30 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 30 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 30

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 30

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 30 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 30.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 30 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 30 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 30 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps - special insulin preparations are available for use in such devices.

How to handle the cartridges

To ensure you get the accurate dose, the Insuman Comb 30 cartridges are to be used only with the following pens:

-JuniorSTAR which delivers doses in steps of 0.5 units

-OptiPen, ClikSTAR, Tactipen, Autopen 24, AllStar or AllStar PRO which deliver doses in steps of 1 unit.

Not all of these pens may be marketed in your country.

The pen should be used as recommended in the information provided by the device manufacturer. The manufacturer’s instructions for using the pen must be followed carefully for loading the cartridge, attaching the injection needle, and administering the insulin injection.

Keep the cartridge at room temperature for 1 or 2 hours before inserting it into the pen. Mix the insulin well and check it before you insert it into the pen. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the cartridge or pen (with the cartridge in it) back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge. A new cartridge with a uniform suspension on mixing must then be used.

Always use a new cartridge if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles (see instructions for using the pen). Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

-Do not re-fill and re-use empty cartridges.

-Do not add any other insulin to the cartridge.

-Do not mix insulin with any other medicines.

Problems with the pen?

Refer to the manufacturer’s instructions for using the pen.

If the insulin pen is damaged or not working properly (due to mechanical defects) it has to be discarded, and a new insulin pen has to be used.

If the pen does not function well, you can draw the insulin from the cartridge into an injection syringe. Therefore, keep injection syringes and needles as well. However, use only those injection syringes which are designed for an insulin concentration of 100 IU (International Units) per ml.

If you use more Insuman Comb 30 than you should

-If you have injected too much Insuman Comb 30, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 30

-If you have missed a dose of Insuman Comb 30 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 30

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 30 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 30 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 30

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the cartridge after “EXP”. The expiry date refers to the last day of that month.

Unopened cartridges

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Comb 30 next to the freezer compartment or a freezer pack. Keep the cartridge in the outer carton in order to protect from light.

In-use cartridges

Cartridges in-use (in the insulin pen) or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The cartridge in-use must not be stored in a refrigerator. Do not use the cartridge after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 30 contains

-The active substance is insulin human. One ml of Insuman Comb 30 contains 100 IU (International Units) of the active substance insulin human. 30% of the insulin is dissolved in water; the other 70% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 30”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 30 looks like and contents of the pack

After mixing, Insuman Comb 30 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 30 is supplied in cartridge containing 3 ml suspension (300 IU). Packs of 3, 4, 5, 6, 9 and 10 cartridges of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

Appel depuis l’étranger : +33 1 57 63 23 23

 

Hrvatska

România

sanofi-aventis Croatia d.o.o.

Sanofi Romania SRL

Tel: +385 1 600 34 00

Tel: +40 (0) 21 317 31 36

Ireland

Slovenija

sanofi-aventis Ireland Ltd. T/A SANOFI

sanofi-aventis d.o.o.

Tel: +353 (0) 1 403 56 00

Tel: +386 1 560 48 00

Ísland

Slovenská republika

Vistor hf.

sanofi-aventis Pharma Slovakia s.r.o.

Sími: +354 535 7000

Tel: +421 2 33 100 100

Italia

Suomi/Finland

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Sanofi Oy

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Puh/Tel: +358 (0) 201 200 300

800 536389 (altre domande)

 

Κύπρος

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sanofi-aventis Latvia SIA

Sanofi

Tel: +371 67 33 24 51

Tel: +44 (0) 845 372 7101

This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 30 SoloStar 100 IU/ml suspension for injection in a pre-filled pen

Insulin human

Read all of this leaflet carefully including the Instructions for Use of Insuman Comb 30 SoloStar, pre-filled pen, before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor,pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 30 is and what it is used for

2.What you need to know before you use Insuman Comb 30

3.How to use Insuman Comb 30

4.Possible side effects

5.How to store Insuman Comb 30

6.Contents of the pack and other information

1. What Insuman Comb 30 is and what it is used for

Insuman Comb 30 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 30 is an insulin preparation with a gradual onset and long duration of action. It comes in cartridges sealed in disposable pen injectors, SoloStar.

Insuman Comb 30 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 30

Do not use Insuman Comb 30

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 30.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise), injection technique as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 30

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 30 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 30 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 30

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 30

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 30 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 30.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 30 is injected under the skin 30 to 45 minutes before a meal.

Method of administration

Insuman Comb 30 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 30 into a vein (blood vessel).

SoloStar delivers insulin in doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

How to handle SoloStar

SoloStar is a pre-filled disposable pen containing insulin human.

Read carefully the "SoloStar Instructions for Use" included in this package leaflet. You must use the pen as described in these Instructions for Use.

A new injection needle must be attached before each use. Only use needles that have been approved for use with SoloStar.

A safety test must be performed before each injection.

Mix the insulin well and check it before first use. Later, you must mix the insulin well again immediately before each injection.

Mixing is best done by gently tilting the pen back and forth at least 10 times. To assist in mixing, three tiny metal balls are present in the cartridge.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the cartridge in the pen. A new pen with a uniform suspension on mixing must then be used.

Always use a new pen if you notice that your blood sugar control is unexpectedly getting worse. If you think you may have a problem with SoloStar, consult your doctor, pharmacist or nurse.

To prevent the possible transmission of disease, each pen must be used by one patient only.

Special care before injection

Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin.

Do not mix insulin with any other medicines. Insuman Comb 30 SoloStar, pre-filled pen, is not designed to allow any other insulin to be mixed in the cartridge.

Empty pens must not be re-filled and must be properly discarded.

Do not use SoloStar if it is damaged or not working properly, it has to be discarded and a new SoloStar has to be used.

If you use more Insuman Comb 30 than you should

-If you have injected too much Insuman Comb 30, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 30

-If you have missed a dose of Insuman Comb 30 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 30

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 30 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 30 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body),

severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 30

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the pen after “EXP”. The expiry date refers to the last day of that month.

Not in-use pens

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put the pre-filled pen next to the freezer compartment or a freezer pack. Keep the pre-filled pen in the outer carton in order to protect from light.

In-use pens

Pre-filled pens in-use or carried as a spare may be stored for a maximum of 4 weeks not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). The pen in-use must not be stored in a refrigerator. Do not use the pen after this time period.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 30 contains

-The active substance is insulin human. One ml of Insuman Comb 30 contains 100 IU (International Units) of the active substance insulin human. 30% of the insulin is dissolved in water; the other 70% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 30”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb30 looks like and contents of the pack

After mixing, Insuman Comb 30 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 30 is supplied in pre-filled pens, SoloStar, containing 3 ml suspension, (300 IU). Packs of 3, 4, 5, 6, 9 and 10 pens of 3 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

Portugal

sanofi-aventis France

Sanofi - Produtos Farmacêuticos, Lda.

Tél: 0 800 222 555

Tel: +351 21 35 89 400

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This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-your insulin pen does not work properly,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 30").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

2.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners

(such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Insuman Comb 30 SoloStar suspension for injection in a pre-filled pen. Instructions for Use.

SoloStar is a pre-filled pen for the injection of insulin. Your doctor has decided that SoloStar is appropriate for you based on your ability to handle SoloStar. Talk with your doctor, pharmacist or nurse about proper injection technique before using SoloStar.

Read these instructions carefully before using your SoloStar. If you are not able to use SoloStar or follow all the instructions completely on your own, you must use SoloStar only if you have help from a person who is able to follow the instructions completely. Hold the pen as shown in this leaflet. To ensure that you read the dose correctly, hold the pen horizontally, with the needle on the left and the dosage selector to the right as shown in the illustrations below.

Follow these instructions completely each time you use SoloStar to ensure that you get an accurate dose. If you do not follow these instructions completely, you may get too much or too little insulin, which may affect your blood glucose.

You can set doses from 1 to 80 units in steps of 1 unit. Each pen contains multiple doses.

Keep this leaflet for future reference.

If you have any questions about SoloStar or about diabetes, ask your doctor, pharmacist or nurse or call the local sanofi-aventis number on the front of this leaflet.

Schematic diagram of the pen

Important information for use of SoloStar:

Always attach a new needle before each use. Only use needles that have been approved for use with SoloStar.

Do not select a dose and/or press the injection button without a needle attached.

Always perform the safety test before each injection (see Step 3).

This pen is only for your use. Do not share it with anyone else.

If your injection is given by another person, special caution must be taken by this person to avoid accidental needle injury and transmission of infection.

Never use SoloStar if it is damaged or if you are not sure that it is working properly.

Always have a spare SoloStar in case your SoloStar is lost or damaged.

Step 1. Check the insulin

ACheck the label on your SoloStar to make sure you have the correct insulin. Insuman SoloStar is white with a colour on the injection button. The injection button colour will vary based on the formulation of Insuman insulin used. The pictures below are for illustrative purposes only.

BTake off the pen cap.

CCheck the appearance of your insulin.

If you are using a suspension insulin (Insuman Basal or Insuman mixtures), turn the pen up and down at least 10 times to resuspend the insulin. Turn the pen gently to avoid foaming in the cartridge.

After mixing check the appearance of your insulin. Insulin suspensions must have an evenly milky-white appearance.

Step 2. Attach the needle

Always use a new sterile needle for each injection. This helps prevent contamination, and potential needle blocks.

Before use of the needle, carefully read the “Instructions for Use” accompanying the needles.

Please note: The needles shown are for illustrative purposes only.

A. Remove the protective seal from a new needle.

B. Line up the needle with the pen, and keep it straight as you attach it (screw or push on, depending on the needle type).

.

If the needle is not kept straight while you attach it, it can damage the rubber seal and cause leakage, or break the needle.

Step 3. Perform a safety test

Always perform the safety test before each injection. This ensures that you get an accurate dose by:

ensuring that pen and needle work properly

removing air bubbles

ASelect a dose of 2 units by turning the dosage selector.

BTake off the outer needle cap and keep it to remove the used needle after injection. Take off the inner needle cap and discard it.

CHold the pen with the needle pointing upwards.

DTap the insulin reservoir so that any air bubbles rise up towards the needle.

EPress the injection button all the way in. Check if insulin comes out of the needle tip.

You may have to perform the safety test several times before insulin is seen.

If no insulin comes out, check for air bubbles and repeat the safety test two more times to remove them.

If still no insulin comes out, the needle may be blocked. Change the needle and try again.

If no insulin comes out after changing the needle, your SoloStar may be damaged. Do not use this SoloStar.

Step 4. Select the dose

You can set the dose in steps of 1 unit, from a minimum of 1 unit to a maximum of 80 units. If you need a dose greater than 80 units, you should give it as two or more injections.

ACheck that the dose window shows “0” following the safety test.

BSelect your required dose (in the example below, the selected dose is 30 units). If you turn past your dose, you can turn back down.

Do not push the injection button while turning, as insulin will come out.

You cannot turn the dosage selector past the number of units left in the pen. Do not force the dosage selector to turn. In this case, either you can inject what is remaining in the pen and complete your dose with a new SoloStar or use a new SoloStar for your full dose.

Step 5. Inject the dose

A Use the injection method as instructed by your doctor, pharmacist or nurse.

BInsert the needle into the skin.

CDeliver the dose by pressing the injection button in all the way. The number in the dose window will return to “0” as you inject.

DKeep the injection button pressed all the way in. Slowly count to 10 before you withdraw the needle from the skin. This ensures that the full dose will be delivered.

The pen plunger moves with each dose. The plunger will reach the end of the cartridge when the total of 300 units of insulin has been used.

Step 6. Remove and discard the needle

Always remove the needle after each injection and store SoloStar without a needle attached. This helps prevent:

Contamination and/or infection

Entry of air into the insulin reservoir and leakage of insulin, which can cause inaccurate dosing.

APut the outer needle cap back on the needle, and use it to unscrew the needle from the pen. To reduce the risk of accidental needle injury, never replace the inner needle cap.

If your injection is given by another person, or if you are giving an injection to another person, special caution must be taken by this person when removing and disposing of the needle. Follow recommended safety measures for removal and disposal of needles (e.g. contact your doctor, pharmacist or nurse) in order to reduce the risk of accidental needle injury and transmission of infectious diseases.

BDispose of the needle safely.

CAlways put the pen cap back on the pen, then store the pen until your next injection.

Storage instructions

Please check the reverse (insulin) side of this leaflet for instructions on how to store SoloStar.

If your SoloStar is in cool storage, take it out 1 to 2 hours before you inject to allow it to warm up to room temperature. Cold insulin is more painful to inject.

Discard your used SoloStar as required by your local authorities.

Maintenance

Protect your SoloStar from dust and dirt.

You can clean the outside of your SoloStar by wiping it with a damp cloth.

Do not soak, wash or lubricate the pen as this may damage it.

Your SoloStar is designed to work accurately and safely. It should be handled with care. Avoid situations where SoloStar might be damaged. If you are concerned that your SoloStar may be damaged, use a new one.

Package leaflet: Information for the user

Insuman Comb 50 100 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 50 is and what it is used for

2.What you need to know before you use Insuman Comb 50

3.How to use Insuman Comb 50

4.Possible side effects

5.How to store Insuman Comb 50

6.Contents of the pack and other information

1.What Insuman Comb 50 is and what it is used for

Insuman Comb 50 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 50 is an insulin preparation with a rapid onset and moderately long duration of action.

Insuman Comb 50 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

2. What you need to know before you use Insuman Comb 50

Do not use Insuman Comb 50

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 50.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 50

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 50 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 50 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 50

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 50

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 50 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 50.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 50 is injected under the skin 20 to 30 minutes before a meal.

Method of administration

Insuman Comb 50 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 50 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for use in such devices.

How to handle the vials

Insuman Comb 50 contains 100 IU insulin per ml. Only injection syringes designed for this insulin concentration (100 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Comb 50 may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Comb 50. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 50 than you should

-If you have injected too much Insuman Comb 50, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 50

-If you have missed a dose of Insuman Comb 50 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 50

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 50 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 50 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body), severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store Insuman Comb 50

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C – 8°C). Do not freeze. Do not put Insuman Comb 50 next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 50 contains

-The active substance is insulin human. One ml of Insuman Comb 50 contains 100 IU (International Units) of the active substance insulin human. 50% of the insulin is dissolved in water; the other 50% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 50”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 50 looks like and contents of the pack

After mixing, Insuman Comb 50 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 50 is supplied in vials containing 5 ml suspension (500 IU). Packs of 1 and 5 vials of 5 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi Belgium

Тел.: +359 (0)2 970 53 00

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika

Magyarország

sanofi-aventis, s.r.o.

SANOFI-AVENTIS Zrt.

Tel: +420 233 086 111

Tel.: +36 1 505 0050

Danmark

Malta

sanofi-aventis Denmark A/S

Sanofi Malta Ltd.

Tlf: +45 45 16 70 00

Tel: +356 21493022

Deutschland

Nederland

Sanofi-Aventis Deutschland GmbH

sanofi-aventis Netherlands B.V.

Tel: +49 (0)180 2 222010

Tel: +31 (0)182 557 755

Eesti

Norge

sanofi-aventis Estonia OÜ

sanofi-aventis Norge AS

Tel: +372 627 34 88

Tlf: +47 67 10 71 00

Ελλάδα

Österreich

sanofi-aventis AEBE

sanofi-aventis GmbH

Τηλ: +30 210 900 16 00

Tel: +43 1 80 185 – 0

España

Polska

sanofi-aventis, S.A.

sanofi-aventis Sp. z o.o.

Tel: +34 93 485 94 00

Tel.: +48 22 280 00 00

France

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This leaflet was last revised in {date}

Other source of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

HYPERGLYCAEMIA AND HYPOGLYCAEMIA

Always carry some sugar (at least 20 grams) with you.

Carry some information with you to show you are diabetic.

HYPERGLYCAEMIA (high blood sugar levels)

If your blood sugar is too high (hyperglycaemia), you may not have injected enough insulin.

Why does hyperglycaemia occur?

Examples include:

-you have not injected your insulin or not injected enough, or if it has become less effective, for example through incorrect storage,

-you are doing less exercise than usual, you are under stress (emotional distress, excitement), or you have an injury, operation, infection or fever,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 50").

Warning symptoms of hyperglycaemia

Thirst, increased need to urinate, tiredness, dry skin, reddening of the face, loss of appetite, low blood pressure, fast heart beat, and glucose and ketone bodies in urine. Stomach pain, fast and deep breathing, sleepiness or even loss of consciousness may be signs of a serious condition (ketoacidosis) resulting from lack of insulin.

What should you do if you experience hyperglycaemia

Test your blood sugar level and your urine for ketones as soon as any of the above symptoms occur. Severe hyperglycaemia or ketoacidosis must always be treated by a doctor, normally in a hospital.

HYPOGLYCAEMIA (low blood sugar levels)

If your blood sugar level falls too much you may become unconscious. Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. You normally should be able to recognise when your blood sugar is falling too much so that you can take the right actions.

Why does hypoglycaemia occur?

Examples include:

-you inject too much insulin,

-you miss meals or delay them,

-you do not eat enough, or eat food containing less carbohydrate than normal (sugar and substances similar to sugar are called carbohydrates; however, artificial sweeteners are NOT carbohydrates),

-you lose carbohydrates due to vomiting or diarrhoea,

-you drink alcohol, particularly if you are not eating much,

-you are doing more exercise than usual or a different type of physical activity,

-you are recovering from an injury or operation or other stress,

-you are recovering from an illness or from fever,

-you are taking or have stopped taking certain other medicines (see section 2, "Other medicines and Insuman Comb 50").

Hypoglycaemia is also more likely to occur if:

-you have just begun insulin treatment or changed to another insulin preparation,

-your blood sugar levels are almost normal or are unstable,

-you change the area of skin where you inject insulin (for example from the thigh to the upper arm),

-you suffer from severe kidney or liver disease, or some other disease such as hypothyroidism.

Warning symptoms of hypoglycaemia

- In your body

Examples of symptoms that tell you that your blood sugar level is falling too much or too fast: sweating, clammy skin, anxiety, fast heart beat, high blood pressure, palpitations and irregular heartbeat. These symptoms often develop before the symptoms of a low sugar level in the brain.

- In your brain

Examples of symptoms that indicate a low sugar level in the brain: headaches, intense hunger, nausea, vomiting, tiredness, sleepiness, sleep disturbances, restlessness, aggressive behaviour, lapses in concentration, impaired reactions, depression, confusion, speech disturbances (sometimes total loss of speech), visual disorders, trembling, paralysis, tingling sensations (paraesthesia), numbness and tingling sensations in the area of the mouth, dizziness, loss of self-control, inability to look after yourself, convulsions, loss of consciousness.

The first symptoms which alert you to hypoglycaemia ("warning symptoms") may change, be weaker or may be missing altogether if

-you are elderly, if you have had diabetes for a long time or if you suffer from a certain type of nervous disease (diabetic autonomic neuropathy),

-you have recently suffered hypoglycaemia (for example the day before) or if it develops slowly,

-you have almost normal or, at least, greatly improved blood sugar levels,

-you have recently changed from an animal insulin to a human insulin such as Insuman,

-you are taking or have taken certain other medicines (see section 2, "Other medicines and Insuman Comb 50").

In such a case, you may develop severe hypoglycaemia (and even faint) before you are aware of the problem. Be familiar with your warning symptoms. If necessary, more frequent blood sugar testing can help to identify mild hypoglycaemic episodes that may otherwise be overlooked. If you are not confident about recognising your warning symptoms, avoid situations (such as driving a car) in which you or others would be put at risk by hypoglycaemia.

What should you do if you experience hypoglycaemia

1.Do not inject insulin. Immediately take about 10 to 20 g sugar, such as glucose, sugar cubes or a sugar-sweetened beverage. Caution: Artificial sweeteners and foods with artificial sweeteners (such as diet drinks) are of no help in treating hypoglycaemia.

2.Then eat something that has a long-acting effect in raising your blood sugar (such as bread or pasta). Your doctor or nurse should have discussed this with you previously.

3.If the hypoglycaemia comes back again take another 10 to 20 g sugar.

4.Speak to a doctor immediately if you are not able to control the hypoglycaemia or if it recurs.

Tell your relatives, friends and close colleagues the following:

If you are not able to swallow or if you are unconscious, you will require an injection of glucose or glucagon (a medicine which increases blood sugar). These injections are justified even if it is not certain that you have hypoglycaemia.

It is advisable to test your blood sugar immediately after taking glucose to check that you really have hypoglycaemia.

Package leaflet: Information for the user

Insuman Comb 50 40 IU/ml suspension for injection in a vial

Insulin human

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

-Keep this leaflet. You may need to read it again.

-If you have any further questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

-If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.What Insuman Comb 50 is and what it is used for

2.What you need to know before you use Insuman Comb 50

3.How to use Insuman Comb 50

4.Possible side effects

5.How to store Insuman Comb 50

6.Contents of the pack and other information

1. What Insuman Comb 50 is and what it is used for

Insuman Comb 50 contains the active substance insulin human which is made by a biotechnology process and is identical with the body's own insulin.

Insuman Comb 50 is an insulin preparation with a rapid onset and moderately long duration of action.

Insuman Comb 50 is used to reduce high blood sugar in patients with diabetes mellitus who need treatment with insulin. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of blood sugar.

1. What you need to know before you use Insuman Comb 50

Do not use Insuman Comb 50

If you are allergic to insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Insuman Comb 50.

Follow closely the instructions for dose, monitoring (blood and urine tests), diet and physical activity (physical work and exercise) as discussed with your doctor.

If you are allergic to this medicine or to animal insulins, talk to your doctor.

Special patient groups

If you have liver or kidneys problems or if you are elderly, speak to your doctor as you may need a lower dose.

Travel

Before travelling, consult your doctor. You may need to talk about

-the availability of your insulin in the country you are visiting,

-supplies of insulin, injection syringes etc.,

-correct storage of your insulin while travelling,

-timing of meals and insulin administration while travelling,

-the possible effects of changing to different time zones,

-possible new health risks in the countries to be visited,

-what you should do in emergency situations when you feel unwell or become ill.

Illnesses and injuries

In the following situations, the management of your diabetes may require a lot of care:

-If you are ill or have a major injury then your blood sugar level may increase (hyperglycaemia).

-If you are not eating enough, your blood sugar level may become too low (hypoglycaemia).

In most cases you will need a doctor. Make sure that you contact a doctor early.

If you have type 1 diabetes (insulin dependent diabetes mellitus), do not stop your insulin and continue to get enough carbohydrates. Always tell people who are caring for you or treating you that you require insulin.

Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Other medicines and Insuman Comb 50

Some medicines cause changes in the blood sugar level (decrease, increase or both depending on the situation). In each case, it may be necessary to adjust your insulin dose to avoid blood sugar levels that are either too low or too high. Be careful when you start or stop taking another medicine.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Before taking a medicine ask your doctor if it can affect your blood sugar level, and what action, if any, you need to take.

Medicines that may cause your blood sugar level to fall (hypoglycaemia) include:

-all other medicines to treat diabetes,

-angiotensin converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure),

-disopyramide (used to treat certain heart conditions),

-fluoxetine (used to treat depression),

-fibrates (used to lower high levels of blood lipids),

-monoamine oxidase (MAO) inhibitors (used to treat depression),

-pentoxifylline, propoxyphene, salicylates (such as aspirin, used to relieve pain and lower fever),

-sulfonamide antibiotics.

Medicines that may cause your blood sugar level to rise (hyperglycaemia) include:

-corticosteroids (such as "cortisone" used to treat inflammation),

-danazol (medicine acting on ovulation),

-diazoxide (used to treat high blood pressure),

-diuretics (used to treat high blood pressure or excessive fluid retention),

-glucagon (pancreas hormone used to treat severe hypoglycaemia),

-isoniazid (used to treat tuberculosis),

-oestrogens and progestogens (such as in the contraceptive pill used for birth control),

-phenothiazine derivatives (used to treat psychiatric disorders),

-somatropin (growth hormone),

-sympathomimetic medicines (such as epinephrine [adrenaline], salbutamol, terbutaline used to treat asthma),

-thyroid hormones (used to treat the thyroid gland disorders),

-protease inhibitors (used to treat HIV),

-atypical antipsychotic medicines (such as olanzapine and clozapine).

Your blood sugar level may either rise or fall if you take:

-beta-blockers (used to treat high blood pressure),

-clonidine (used to treat high blood pressure),

-lithium salts (used to treat psychiatric disorders).

Pentamidine (used to treat some infections caused by parasites) may cause hypoglycaemia which may sometimes be followed by hyperglycaemia.

Beta-blockers like other sympatholytic medicines (such as clonidine, guanethidine, and reserpine) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

If you are not sure whether you are taking one of those medicines ask your doctor or pharmacist.

Insuman Comb 50 with alcohol

Your blood sugar levels may either rise or fall if you drink alcohol.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Inform your doctor if you are planning to become pregnant, or if you are already pregnant. Your insulin dose may need to be changed during pregnancy and after giving birth. Particularly careful control of your diabetes, and prevention of hypoglycaemia, is important for the health of your baby. However, there is no experience with the use of Insuman Comb 50 in pregnant women.

If you are breast-feeding consult your doctor as you may require adjustments in your insulin doses and your diet.

Driving and using machines

Your ability to concentrate or react may be reduced if:

-you have hypoglycaemia (low blood sugar levels),

-you have hyperglycaemia (high blood sugar levels),

-you have problems with your sight.

Keep this possible problem in mind in all situations where you might put yourself and others at risk (such as driving a car or using machines). You should contact your doctor for advice on driving if:

-you have frequent episodes of hypoglycaemia,

-the first warning symptoms which help you to recognise hypoglycaemia are reduced or absent.

Important information about some of the ingredients of Insuman Comb 50

This medicine contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to use Insuman Comb 50

Dose

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Based on your life-style and the results of your blood sugar (glucose) tests, your doctor will

-determine how much Insuman Comb 50 per day you will need,

-tell you when to check your blood sugar level, and whether you need to carry out urine tests,

-tell you when you may need to inject a higher or lower dose of Insuman Comb 50.

Many factors may influence your blood sugar level. You should know these factors so that you are able to react correctly to changes in your blood sugar level and to prevent it from becoming too high or too low. See the box at the end of this leaflet for further information.

Frequency of administration

Insuman Comb 50 is injected under the skin 20 to 30 minutes before a meal.

Method of administration

Insuman Comb 50 is a fluid (suspension) for injection under the skin.

Do NOT inject Insuman Comb 50 into a vein (blood vessel).

Your doctor will show you in which area of the skin you should inject your insulin. With each injection, change the puncture site within the particular area of skin that you are using.

Do not use it in insulin pumps or other infusion pumps – special insulin preparations are available for use in such devices.

How to handle the vials

Insuman Comb 50 contains 40 IU insulin per ml. Only injection syringes designed for this insulin concentration (40 IU per ml) must be used. The injection syringes must not contain any other medicines or traces of medicines (such as traces of heparin).

Before the first withdrawal of insulin you must remove the safety tear-off lid on the vial.

Mix the insulin well immediately before each injection. This is best done by rolling the vial tilted between the palms of the hands. Do not shake the vial vigorously as this could damage the insulin and cause froth to form. Froth can make it difficult for you to measure the correct dose.

After mixing, the suspension must have a uniform milky-white appearance. It must not be used if it remains clear or if, for example, clumps, flakes, particles or anything similar are in the suspension or on the sides or bottom of the vial. A new vial with a uniform suspension on mixing must then be used.

Always use a new vial if you notice that your blood sugar control is unexpectedly getting worse. This is because the insulin may have lost some of its effectiveness. If you think you may have a problem with your insulin, have it checked by your doctor or pharmacist.

Special care before injection

Before injection remove any air bubbles. Make sure that neither alcohol nor other disinfectants or other substances contaminate the insulin. Do not mix insulin with any other medicines except with insulin human preparations as detailed below.

Insuman Comb 50 may be mixed with all insulin human preparations, EXCEPT those specially designed for use in insulin pumps. Also, it must NOT be mixed with animal source insulins or insulin analogues.

Your doctor will tell you if you have to mix insulin human preparations. If you need to inject a mixture, draw the other insulin into the injection syringe before Insuman Comb 50. Inject as soon as you have mixed them. Do not mix insulins of different strengths (for example 100 IU per ml and 40 IU per ml).

If you use more Insuman Comb 50 than you should

-If you have injected too much Insuman Comb 50, your blood sugar level may become too low (hypoglycaemia). Check your blood sugar frequently. In general, to prevent hypoglycaemia you must eat more food and monitor your blood sugar. For information on the treatment of hypoglycaemia, see box at the end of this leaflet.

If you forget to use Insuman Comb 50

-If you have missed a dose of Insuman Comb 50 or if you have not injected enough insulin, your blood sugar level may become too high (hyperglycaemia). Check your blood sugar frequently. For information on the treatment of hyperglycaemia, see box at the end of this leaflet.

-Do not take a double dose to make up for a forgotten dose.

If you stop using Insuman Comb 50

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop Insuman Comb 50 without speaking to a doctor, who will tell you what needs to be done.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Insulin Mix-ups

You must always check the insulin label before each injection to avoid mix-ups between Insuman Comb 50 and other insulins.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Most serious side effects

Side effects reported uncommonly (may affect up to 1 in 100 people)

Severe allergic reaction with low blood pressure (shock)

Side effects reported with a frequency not known (cannot be estimated from the available data)

The most frequent side effect is hypoglycaemia (low blood sugar). Serious hypoglycaemia may cause a heart attack or brain damage and may be life-threatening. For further information on the side effects of low blood sugar or high blood sugar, see the box at the end of this leaflet.

Severe allergic reactions to insulin may occur which may become life-threatening. Such reactions to insulin or to the excipients can cause large-scale skin reactions (rash and itching all over the body),

severe swelling of skin or mucous membranes (angiooedema), shortness of breath, a fall in blood pressure with rapid heart beat and sweating.

Other side effects

Side effects reported commonly (may affect up to 1 in 10 people)

Oedema

Insulin treatment may cause temporary build-up of water in the body with swelling in the calves and ankles.

Injection site reactions

Side effects reported uncommonly

Injection site urticaria (itchy rash)

Side effects reported with a frequency not known

Sodium retention

Eye reactions

A marked change (improvement or worsening) in your blood sugar control can disturb your vision temporarily. If you have proliferative retinopathy (an eye disease related to diabetes) severe hypoglycaemic attacks may cause temporary loss of vision.

Skin changes at the injection site (lipodystrophy)

If you inject your insulin too often at the same skin site, fatty tissue under the skin at this site may either shrink or thicken. Insulin that you inject in such a site may not work very well. Changing the injection site with each injection may help to prevent such skin changes.

Skin and allergic reactions

Other mild reactions at the injection site (such as injection site redness, unusually intense pain on injection site, itching, injection site swelling or injection site inflammation) may occur. They can also spread around the injection site. Most minor reactions to insulins usually resolve in a few days to a few weeks.

Insulin antibodies

Insulin treatment can cause the body to produce antibodies to insulin (substances that act against insulin). However, only very rarely, this will require a change to your insulin dose.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Insuman Comb 50

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of that month.

Unopened vials

Store in a refrigerator (2°C - 8°C). Do not freeze. Do not put Insuman Comb 50 next to the freezer compartment or a freezer pack. Keep the vial in the outer carton in order to protect from light.

Opened vials

Once in-use, the vial may be stored for a maximum of 4 weeks in the outer carton not above 25°C and away from direct heat (for example next to a heating unit) or direct light (direct sunlight or next to a lamp). Do not use the vial after this time period. It is recommended that the date of the first use be noted on the label.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Insuman Comb 50 contains

-The active substance is insulin human. One ml of Insuman Comb 50 contains 40 IU (International Units) of the active substance insulin human. 50% of the insulin is dissolved in water; the other 50% is present as tiny crystals of insulin protamine.

-The other ingredients are: protamine sulphate, metacresol, phenol, zinc chloride, sodium dihydrogen phosphate dihydrate, glycerol, sodium hydroxide (see section 2 under “Important information about some of the ingredients of Insuman Comb 50”), hydrochloric acid (for pH adjustment) and water for injections.

What Insuman Comb 50 looks like and contents of the pack

After mixing, Insuman Comb 50 is a uniformly milky fluid (suspension for injection), with no clumps, particles or flocculation visible.

Insuman Comb 50 is supplied in vials containing 10 ml suspension (400 IU). Packs of 1 and 5 vials of 10 ml are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Sanofi Belgium

UAB «SANOFI-AVENTIS LIETUVA»

Tél/Tel: +32 (0)2 710 54 00

Tel: +370 5 2755224

България

Luxembourg/Luxemburg

SANOFI BULGARIA EOOD

Sanofi