Article Contents
- 1. NAME OF THE MEDICINAL PRODUCT
- 2. QUALITATIVE AND QUANTITATIVE COMPOSITION
- 3. PHARMACEUTICAL FORM
- 4.1
- 4.2
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5.1
- 5.2Medicinal Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6.1
- 6.2
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. MARKETING AUTHORISATION HOLDER
- 8. MARKETING AUTHORISATION NUMBER(S)
- 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
- 10. DATE OF REVISION OF THE TEXT
1. NAME OF THE MEDICINAL PRODUCT
Velosulin 100 IU/ml solution for injection or infusion in a vial.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Insulin human, rDNA (produced by recombinant DNA technology in Saccharomyces cerevisiae).
One IU (International Unit) corresponds to 0.035 mg of anhydrous humanauthorisedinsulin.
3. PHARMACEUTICAL FORM
Clear, colourless, aqueous solution. |
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4. | CLINICAL PARTICULARS |
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4.1 | Therapeutic indications | no | ||
Treatment of diabetes mellitus. | ||||
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4.2 |
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Posology and method of administration |
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This
Velosulin is a
products. For incompatibilities see section 6.2.
DosageMedicinal
Dosage is individual and determined by the physician in accordance with the needs of the patient. Usually,
In general, when patients are transferred from injection to infusion therapy, it may be advisable to reduce the dosage by initiating the patient at 90% of the previous total daily dosage, with 40% as basal rate and 50% as boluses divided between the three main meals.
Dosage is individual and determined in accordance with the needs of the patient. The individual insulin requirement is usually between 0.3 and 1.0 IU/kg/day. The daily insulin requirement may be higher in patients with insulin resistance (e.g. during puberty or due to obesity) and lower in patients with residual, endogenous insulin production.
In patients with diabetes mellitus optimised glycaemic control delays the onset of late diabetic complications. Close blood glucose monitoring is therefore recommended.
An injection or infusion should be followed within 30 minutes by a meal or snack containing carbohydrates.
Dosage adjustment
Concomitant illness, especially infections and feverish conditions, usually increases the patient's insulin requirement.
Renal or hepatic impairment may reduce insulin requirement.
Adjustment of dosage may also be necessary if patients change physical activity or their usual diet.
For subcutaneous or intravenous use.
Dosage adjustment may be necessary when transferring patients from one insulin preparation to another (see section 4.4 ).authorised Administration
Insulin infusion (CSII):
Continuous subcutaneous insulin infusion (CSII) in external insulin infusion pumps is usually administered in the abdominal wall. Velosulin should never be mixed with any other insulin products when used in a pump.
Patients started on CSII must receive comprehensive instructionlongerin the use of the pump, and the necessary actions in case of illness, hypoglycaemia, hyperglycaemia or pump failure.
The patient should read and follow the instructions that accompany the infusion pump and use the correct reservoir and catheter for the pump (see section 6.6).
The infusion set should be changed every 48 hours using aseptic technique when inserting the infusion set.
When filling a new syringe, no large air bubbles should be left in either the syringe or the catheter. The patient should follow the instructions from the physician about the basal infusion rate and the
mealtime insulin boluses to be taken. | no |
To get the benefit of insulinproductinfusion, and to detect possible malfunction of the pump, the patient should measure his blood glucose level regularly.
In the event of a hypoglycaemic episode, the infusion should be stopped until the episode is resolved. If repeated or severe low blood glucose levels occur, the patient should notify the health care professional and the need to reduce or stop the insulin administration should be considered. A pump
available in case of emergency or pump interruption or failure, in order that insulin can be administered by subcutaneous injection.
malfunction or obstruction of the infusion set can result in a rapid rise in glucose levels. If the patient suspectsMedicinalan interruption to insulin flow the patient should notify the health care professional. Patients administering Velosulin by CSII must have injection syringes and alternative insulin readily
Insulin injection:
Administration of Velosulin is also possible by subcutaneous or intravenous injection. Intravenous administration should only be carried out by health care professionals.
Velosulin is administered subcutaneously in the abdominal wall. The thigh, the gluteal region or the deltoid region may also be used.
Subcutaneous injection into the abdominal wall ensures a faster absorption than from other injection sites.
Injection into a lifted skin fold minimises the risk of unintended intramuscular injection.
The needle should be kept under the skin for at least 6 seconds to make sure the entire dose is injected.
Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy.
- Ultratard - insulin human
- Mixtard - insulin human
- Protaphane - insulin human
- Actraphane - insulin human
- Insuman - insulin human
- Exubera - insulin human
Prescription drugs listed. Substance: "Insulin human"
The vials may be used with insulin syringes with a corresponding unit scale. When two types of insulin are mixed, draw the amount of
Velosulin is accompanied by a package leaflet with detailed instruction for use to be followed.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients (see section 6.1). Hypoglycaemia.
4.4 Special warnings and precautions for use | authorised |
mouth, loss of appetite as well as acetone odour of breath. |
Inadequate dosage or discontinuation of treatment, especially in type 1 diabetes, may lead to hyperglycaemia.
Usually, the first symptoms of hyperglycaemia set in gradually, over a period of hours or days. They include thirst, increased frequency of urination, nausea, vomiting, drowsiness, flushed dry skin, dry
In type 1 diabetes, untreated hyperglycaemic events eventually lead to diabetic ketoacidosis, which is potentially lethal.
Due to the lack of
an insulin pump are at risk of fast development of ketoacidosis in case of prolonged interruption of | ||
continuous subcutaneous insulin infusion. | no | longer |
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Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement (see sections 4.8 and 4.9).
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.
Patients whose blood glucose control is greatly improved e.g. by intensified insulin therapy, may | |
experience a change in their usual warning symptoms of hypoglycaemia and should be advised | |
accordingly. |
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Usual warning symptoms may disappear in patients with longstanding diabetes. | |
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Transferring a patient to another type or brand of insulin should be done under strict medical |
animal source insulin) may result in a need for a change in dosage. If an adjustment is needed when switching the patients to Velosulin, it may occur with the first dose or during the first several weeks or months.
supervision.MedicinalChanges in strength, brand (manufacturer), type
As with any insulin therapy, injection site reactions may occur and include pain, itching, hives, swelling and inflammation. Continuous rotation of the injection site within a given area may help to reduce or prevent these reactions. Reactions usually resolve in a few days to a few weeks. On rare occasions, injection site reactions may require discontinuation of Velosulin.
A few patients who have experienced hypoglycaemic reactions after transfer from animal source insulin have reported that early warning symptoms of hypoglycaemia were less pronounced or different from those experienced with their previous insulin.
Before travelling between different time zones, the patient should be advised to consult the physician, since this may mean that the patient has to take insulin and meals at different times.
Patients using CSII may be more prone to infection at the site of infusion. Infections can be minimised by careful attention to personal hygiene of the hands and infusion site and by frequent changes of catheter (maximum usage 2 days).
Velosulin contains metacresol, which may cause allergic reactions.
4.5 Interaction with other medicinal products and other forms of interaction
A number of medicinal products are known to interact with glucose metabolism. The physician must therefore take possible interactions into account and should always ask his patients about any
medicinal products they take.
Oral hypoglycaemic agents (OHA), monoamine oxidase inhibitors (MAOI),
The following substances may reduce insulin requirement: authorised
The following substances may increase insulin requirement:
Oral contraceptives, thiazides, glucocorticoids, thyroid hormones and
Octreotide/lanreotide may both decrease and increase insulin requirement.
Alcohol may intensify and prolong the hypoglycaemic effect of insulin.
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4.6Pregnancy and lactation
product | no |
There are no restrictions on treatment of diabetes with insulin during pregnancy, as insulin does not pass the placental barrier.
Both hypoglycaemia and hyperglycaemia, which can occur in inadequately controlled diabetes therapy, increase the risk of malformations and death in utero. Intensified control in the treatment of pregnant women with diabetes is therefore recommended throughout pregnancy and when
contemplating pregnancy.
After delivery, insulin requirements return rapidly to
InsulinMedicinalrequirements usually fall in the first trimester and subsequently increase during the second and third trimesters.
Insulin treatment of the nursing mother presents no risk to the baby. However, the Velosulin dosage may need to be adjusted.
4.7 Effects on ability to drive and use machines
The patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery).
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.
- Levemir - Novo Nordisk A/S
- Actraphane - Novo Nordisk A/S
- Xultophy - Novo Nordisk A/S
- Mixtard - Novo Nordisk A/S
- Prandin - Novo Nordisk A/S
- Refixia - Novo Nordisk A/S
Prescription drugs listed. Manufacturer: "Novo Nordisk A/S"
4.8 Undesirable effects
As for other insulin products, in general, hypoglycaemia is the most frequently occurring undesirable effect. It may occur if the insulin dose is too high in relation to the insulin requirement. In clinical trials and during marketed use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency can be presented. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death.
Frequencies of adverse drug reactions from clinical trials that are considered related to | |
Eye disorders | authorised |
human insulin (Actrapid) are listed below. The frequencies are defined as: uncommon (≥1/1,000 to
<1/100). Isolated spontaneous cases are presented as very rare defined as <1/10,000 including isolated reports.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Nervous system disorders Uncommon - Peripheral neuropathy
Fast improvement in blood glucose control may be associated with a condition termed “acute painful neuropathy”, which is usually reversible.
Uncommon - Refraction disorders
Refraction anomalies may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.
Very rare - Diabetic retinopathy | no |
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be
Uncommon – Lipodystrophy
associated with temporary worsening of diabetic retinopathy. Skin and subcutaneous tissueproductdisorders
Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
General disorders and administration site conditions
UncommonMedicinal- Injection site reactions
Injection site reactions (redness, swelling, itching, pain and haematoma at the injection site) may
occur during treatment with insulin. Most reactions are transitory and disappear during continued treatment.
Uncommon - Oedema
Oedema may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.
Immune system disorders
Uncommon - Urticaria, rash
Very rare - Anaphylactic reactions
Symptoms of generalised hypersensitivity may include generalised skin rash, itching, sweating, gastrointestinal upset, angioneurotic oedema, difficulties in breathing, palpitation, reduction in blood pressure and fainting/loss of consciousness. Generalised hypersensitivity reactions are potentially life- threatening.
4.9 Overdose
A specific overdose of insulin cannot be defined. However, hypoglycaemia may develop over sequential stages:
binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.
• | Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary | |
| products. It is therefore recommended that the diabetic patients carry some sugar lumps, sweets, | |
| biscuits or sugary fruit juice. |
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• | Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by | |
| glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a person who has received | |
| appropriate instruction, or by glucose given intravenously by a medical professional. Glucose | |
| must also be given intravenously, if the patient does not respond to glucagon within 10 to | |
| 15 minutes. |
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| Upon regaining consciousness, administration of oral carbohydrate is recommended for the | |
| patient in order to prevent relapse. |
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5. | PHARMACOLOGICAL PROPERTIES |
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5.1 | Pharmacodynamic properties |
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Pharmacotherapeutic group: insulins and analogues for injection, | ||
code: A10A B01. |
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The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following | ||
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A clinical trial in a single intensive care unit treatingnohyperglycaemia (blood glucose above
10 mmol/l) in 204 diabetic and 1344
Velosulin is a
When Velosulin is administered as a bolus injection onset of action is within ½ hour, reaches a maximum effect within
5.2MedicinalPharmacokinetic properties
Insulin in the blood stream has a
This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulin products are therefore affected by significant intra- and
Continuous subcutaneous infusion eliminates some of the variations/fluctuations inherent to injection therapy.
The relatively fast absorption of soluble insulin ensures a constant supply of insulin to the blood from a relatively small pool under the skin.
Absorption
The maximum plasma concentration is reached within
Distribution
- Actrapid - A10AB01
Prescription drugs listed. ATC Code: "A10AB01"
No profound binding to plasma proteins, except circulating insulin antibodies (if present) has been observed.
Metabolism
Human insulin is reported to be degraded by insulin protease or
Elimination | authorised |
importance of individual dose titration. |
The terminal
Chrildren and adolescents
The pharmacokinetic profile has been studied in a small number (n=18) of diabetic children (aged 6- 12 years) and adolescents (aged
5.3Preclinical safety data
Insulin products should only be added to compounds with which it is known to be compatible. Medicinal products added to the insulin solution may cause degradation of the insulin, e.g. if the medicinal products contain thiols or sulphites.
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction. | ||||
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6. | PHARMACEUTICAL PARTICULARS |
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6.1 | List of excipients |
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Zinc chloride |
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Glycerol |
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Metacresol |
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Disodium phosphate dihydrate |
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Sodium hydroxide (for pH adjustment) |
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Hydrochloric acid (for pH adjustment) |
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Water for injections |
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6.2 | Incompatibilities |
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Medicinal |
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Concerning compatibility with insulin infusion pumps, reservoirs, catheters and needles, see section 6.6.
6.3Shelf life
30 months when stored between 2°C - 8°C.
6 weeks when used or stored at room temperature (below 25°C).
After first use as infusion, the insulin solution may be stored in the pump reservoir for six days at up to 37°C (close to the body).
6.4 Special precautions for storage
Before use: store in a refrigerator (2°C - 8°C).
Do not store them in or too near the freezer section or cooling element.
Do not freeze.
During use: do not refrigerate. Do not store above 25°C.
After first use as infusion: the insulin solution may be stored in the pump reservoir at up to 37°C (close to the body).
6.5 Nature and contents of container | authorised |
Not all pack sizes may be marketed. | |
10 ml glass vial (type 1) closed with a bromobutyl/polyisoprene rubber stopper and a protective |
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Pack sizes: 1 and 5 vials x 10 ml and a multipack with 5 x (1 x 10 ml) vials. | |
recommended. | longer |
6.6 Special precautions for disposal and other handling |
Upon mixing Velosulin with infusion fluids an unpredictable amount of insulin will be absorbed to | |
the infusion material. Monitoring of the patient's blood glucose during infusion is therefore | |
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When administered by CSII no other medicinal products or other insulin products should be mixed in | |
product |
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the reservoir of the infusion pump with Velosulin.
When combination with
InsulinMedicinalpreparations which have been frozen must not be used.
Insulin solutions should not be used if they do not appear water clear and colourless.
Insulin infusion (CSII):
Use only syringes made of polyethylene, polypropylene or glass.
Use only catheters where the material in contact with the insulin is made of polyethylene or polypropylene.
Use only
Any unused product or waste material should be disposed of in accordance with local requirements.
7.MARKETING AUTHORISATION HOLDER
Novo Nordisk A/S
Novo Allé
Denmark
8. MARKETING AUTHORISATION NUMBER(S)
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first suthorisation: 07 October 2002
Date of latest renewal: 18 September 2007 |
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10. DATE OF REVISION OF THE TEXT |
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