English
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Unituxin (dinutuximab) – Package leaflet - L01XC

Updated on site: 10-Oct-2017

Medication nameUnituxin
ATC CodeL01XC
Substancedinutuximab
ManufacturerUnited Therapeutics Europe Ltd
What Unituxin is

Package leaflet: Information for the user

Unituxin 3.5 mg/mL concentrate for solution for infusion dinutuximab

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Occasionally a young person who is taking this medicne may be reading the package leaflet, but usually it will be a parent/carer. Nevertheless the leaflet will refer to ‘you’ throughout.

Read all of this leaflet carefully before you start taking 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 or nurse.

 

-

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed

 

in this leaflet. See section 4.

 

 

authorised

What is in this leaflet

 

 

 

 

 

1.

What Unituxin is and what it is used for

 

 

 

2.

What you need to know before you are given Unituxin

 

3.

How Unituxin will be given

 

longer

 

4.

Possible side effects

 

 

 

 

 

5.

How to store Unituxin

 

 

 

6.

Contents of the pack and other information

no

 

 

1.

What Unituxin is and what it is used for

 

 

 

 

 

They help the immune system to target certain cells, such as cancer cells, by ‘sticking’ to them.

Unituxin is a cancer medicine that containsproductthe active substance dinutuximab. It belongs to a group of medicines called ‘monoclonal antibodies’. These work like the antibodies produced naturally by the body.

What Unituxin is usedMedicinalfor

Unituxin is used to treat ‘high-risk neuroblastoma’ in babies, children and adolescents aged 12 months to 17 years old.

Neuroblastoma is a type of cancer that grows from abnormal nerve cells in the body. Some neuroblastomas are classed as ‘high risk’ if the cancer has spread to various parts of the body and contains certain types of cells. High-risk neuroblastomas are more likely to come back again after treatment.

To reduce the risk of the cancer coming back, Unituxin is given at the last stage of the treatment to eliminate small amounts of disease which may still be present after the cancer has responded to chemotherapy, surgery, and an autologous (self-donating) blood cell transplant.

How Unituxin works

Unituxin recognises and attaches to a cell surface target called ‘GD2’. GD2 is found on the surface of neuroblastoma cells. When Unituxin attaches to the GD2 on the cancer cells, the patient’s immune system starts to attack these cells and kill them.

Unituxin has been shown to delay the progression or relapse of the disease and to increase survival.

2. What you need to know before you are given Unituxin

Do not take Unituxin if

- you are allergic to dinutuximab or any of the other ingredients of this medicine (listed in section 6). If you are not sure, talk to your doctor or nurse before you are given dinutuximab.

Warnings and precautions

Talk to your doctor or nurse before you are given Unituxin if:

-you have ever had fits (convulsions)

-you have liver problems

-you have a low number of white blood cells or platelets in your blood – shown in tests

-you have breathing problems such as shortness of breath when resting

-you have kidney problems

-you have any infections.

If any of the above apply to you (or you are not sure), talk to your doctor or nurse before being given

Unituxin.

You might notice the following when you first receive Unituxin and authorisedduring the course of treatment:

• Allergic reactions, which may be severe (anaphylactic reactions), other reactions to the infusion – Tell your doctor or nurse straight away if you have any kind of reaction during or after

the infusion. These are very common (affecting more than 1 in 10 people). Signs of an allergic reaction may include skin rash, hives, swelling inlongerthe face or throat, dizziness, a rapid heart beat or

palpitations, being short of breath and difficulty breathing, fever, feeling sick, aches and pains in your joints. You will be closely monitored for these si ns while being given the medicine. You will be given an anti-histamine medicine which helps to prevent allergic reactions.

Capillary Leak Syndrome due to leakage of bl od components through small blood vessel walls -

 

this may cause rapid swelling to arms, legs andnoother parts of your body, rapid drop in blood

 

pressure, lightheadedness and breathing difficulties

Pain – tell your doctor or nurse if y get any pain. This is very common during treatment

 

(affecting more than 1 in 10 eo le). You will be given pain relieving medicines (such as

 

product

 

paracetamol, ibuprofen and morphine) to help prevent and reduce the pain. See section 4 for more

• Low blood pressureMedicinal– this may make you feel dizzy or faint.

• Problems with your eyes – tell your doctor or nurse if you notice any problems with your eyes or changes to your vision.

• Infections of the blood – tell your doctor if you notice fever, shaking chills, or feel faint or dizzy.

• Problems with your nerves – you may notice numbness, tingling or burning in your hands, feet, legs or arms, reduced sensation or weakness with movement (peripheral neuropathy).

See section 4 for a full list of known side effects.

Tests and checks

Your doctor will do blood tests and may do eye tests while you are taking this medicine.

Other medicines and Unituxin

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. This includes medicines obtained without a prescription and herbal medicines.

In particular, tell your doctor or nurse if you have recently received:

-medicines called ‘corticosteroids’ – these can affect the activity of your immune system which is important for Unituxin to work.

-‘intravenous immunoglobulin’ – you should not have this type of medicine in the two weeks before

Unituxin treatment and for at least one week after treatment has finished.

If any of the above apply to you (or you are not sure), tell your doctor or nurse before you are given Unituxin.

Pregnancy

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before being given this medicine.

If it is possible for you to become pregnant and you are not using contraception, talk to your doctor before being given this medicine.

It is recommended to use contraception for 6 months after discontinuation of this medicine.

Breast-feeding

If you are breastfeeding, talk to your doctor or nurse before being given this medicine.

Unituxin contains sodium

You should not breastfeed during treatment with this medicine. This because it is not known if the

 

 

 

authorised

medicine can pass into breast-milk. The recommended int rval time between treatment discontinuation

and breastfeeding is 6 months.

 

longer

 

Driving and using machines

 

 

 

 

 

Unituxin has many side effects, and this will affect your ability to drive and use machines

 

no

 

 

 

product

 

 

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means it is essentially ‘sodiumfree’.

3. How Unituxin willMedicinalbe given

Unituxin will be given to you by doctor or nurse while you are in hospital. It is given as a drip into one of your veins (intravenous infusion).

Unituxin is used with three other medicines:

-Isotretinoin

-GM-CSF

-IL-2

These medicines will be given to you over six courses. Each course lasts one month. You will not be given all of the medicines in every course.

How much is given

Unituxin will be given to you in five of the six courses. The recommended dose is 17.5 mg/m2. Your doctor will work out your dose based on your body surface area.

During courses (months) 1, 3 and 5

Unituxin is given as a drip into one of your veins – for about 10 hours each day for four days.

GM-CSF is given as either an injection under the skin or as a drip into one of your veins each day for 14 days.

You will be given isotretinoin to take by mouth for the last 14 days of each course.

During courses (months) 2 and 4

Unituxin is given as a drip into one of your veins – for about 10 hours each day for four days.

IL-2 is given as a drip into one of your veins for four days in a row (continuous infustion) – for the first four days of the first week and the first four days of the second week of each course.

You will be given isotretinoin to take by mouth for the last 14 days of each course.

During course (month) 6

You will only be given isotretinoin to take by mouth.

Your doctor or nurse will check you during and after the infusion. To reduce the risk of side effects, your doctor may increase the time allowed for the Unituxin infusion up to 20 hours. If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Tell your doctor or nurse straight away if you notice the following:

Like all medicines, this medicine, which is given with GM-CSF, IL-2authorisedand isotretinoin can cause side effects, although not everybody gets them.

• Any kind of allergic reaction or other reaction at the injection site – symptoms may include a skin rash, hives, swelling in the face or throat, dizziness, a rapidlongerheart b at palpitations, being short of breath and difficulty breathing, fever, feeling sick, aches and pains in your joints .

Rapid swelling of the arms, legs and other parts of your body, rapid drop in blood pressure, lightheadedness and breathing difficulties (Capillary Leak Syndrome).

Any kind of pain: in the stomach, throat, chest, face, hands, feet, legs or arms (such as numbness, tingling or burning) back, neck, joint, bone, muscle, mouth, eye, genitals.

These are very common (may affect moreproductthan 1 in 10 people).

If you notice any of theseMedicinaleffects, te your doctor or nurse straight away.

Other side effects that you may experience with this medicine include:

Very common side eff cts (may affect more than 1 in 10 people):

-cough

-itching

-loss of appetite

-diarrhoea, being sick

-low blood pressure that may make you feel dizzy or faint or high blood pressure

-abnormal blood tests such as low platelets, low red or white blood cells, low level of albumin (this can cause swelling and make you feel weak and tired), abnormal liver function, low level of potassium, sodium, calcium, phosphates, or high level of glucose.

Common side effects (may affect up to 1 in 10 people):

-weight loss, weight gain

-chills

-headache

-feeling tired, irritable

-constipation, blood in stools

-damage to the nerves around the body which may affect movement

-blurred vision, being sensitive to light, the pupils of your eyes staying large (‘dilated’)

-not being able to urinate, blood or protein in your urine

-higher risk of getting infections especially from the devices used to give you the medicine, blood or gut infections

-skin problems where the injection was given, a red rash with small bumps

-abnormal blood tests such as low levels of magnesium, glucose, high level of acids or creatinine.

Uncommon side effects (may affect up to 1 in 100 people ):

-unequal pupils

-fluid in or around the lungs

-kidney failure

-over-active thyroid

-serum sickness – an illness similar to an allergy

-abnormal heart rhythm

-swelling in the back part of the brain (Posterior Reversible Encephalopathy Syndrome) – symptoms may include high blood pressure, headache, fits, change in vision or behaviour, feeling drowsy or tired.

-atypical haemolytic uraemic syndrome (aHUS) – an illness that affects the blood system and kidney – symptoms may include flu-like symptoms that do not go away, confusion, lethargy, loss of appetite, or dark coloured urine.

Reporting of side effects

If you get any side effects, talk to your doctor 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 Unituxin

 

 

authorised

 

 

 

 

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

 

 

Do not use this medicine after the expiry date which is statedlongerthe carton after EXP. The expiry date refers

to the last day of that month.

no

 

 

Store in a refrigerator (2 °C – 8 °C). Doproductnot freeze. Keep the vial in the outer carton in order to protect from light.

a microbiological pointMedicinalof view, the diluted solution should be used immediately.

Chemical and physical -use stability has been demonstrated at ambient conditions (less than 25 °C). From

Do not use this medicine if you notice any particulate matter or discolouration prior to administration.

Do not throw away any medicines via wastewater or household waste. The doctor or nurse will throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Unituxin contains

-The active substance is dinutuximab. Each vial contains 17.5 mg of dinutuximab in 5 mL. Each mL of concentrate contains 3.5 mg of dinutuximab.

-The other ingredients are histidine, polysorbate 20 (E 432), sodium chloride and water for injection. See section 2 for further information about sodium.

What Unituxin looks like and contents of the pack

Unituxin is a clear, colourless solution for infusion, provided in a clear glass vial. One carton contains one vial.

Marketing Authorisation Holder and Manufacturer

United Therapeutics Europe, Ltd.

Unither House

Curfew Bell Road

Chertsey

Surrey

KT16 9FG

United Kingdom

Tel: +44 (0)1932 664884

Fax: +44 (0)1932 573800

E-mail: druginfo@unither.com

This leaflet was last revised in

 

 

 

 

Other sources of information

 

 

 

 

Detailed information on this medicine is available on the European Medicines Agency web site:

 

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.

 

This leaflet is available in all EU/EEA languages on the European Medicines Ag ncy website.

 

<-----------------------------------------------------------------------------------------------------------------------------

 

 

authorised

>

Posology and method of administration

 

 

 

 

 

 

 

Unituxin is restricted to hospital-use only and must be administ d under the supervision of a physician

 

experienced in the use of oncological therapies. It must be administered by a healthcare professional

 

prepared to manage severe allergic reactions including anaphylaxis in an environment where full

 

resuscitation services are immediately available.

no

longer

 

 

Posology

 

 

 

Unituxin is to be administered by intravenproductus infusion over five courses at a daily dose of 17.5 mg/m2. It is Days 8–11 during Courses 2 and 4 (each course lasting approximately 28 days).

administered on Days 4–7 during Courses 1, 3, and 5 (each course lasting approximately 24 days) and on

 

 

Medicinal

 

 

 

 

 

 

 

 

 

 

 

The treatment regimen cons sts of dinutuximab, GM-CSF, IL-2, and isotretinoin, administered over six

 

consecutive courses. The complete dosing regimen is outlined in Table 1 and Table 2.

 

 

 

Table 6: Courses 1, 3, and 5 dosing schedule for Unituxin, GM-CSF and isotretinoin

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Day

15-24

GM-CSF1

X

X

X

X

X

X

X

X

X

X

X

X

X

X

 

Dinutuximab2

 

 

 

X

X

X

X

 

 

 

 

 

 

 

 

Isotretinoin3

 

 

 

 

 

 

 

 

 

 

X

X

X

X

X

1.Granulocyte macrophage colony-stimulating factor (GM-CSF): 250 μg/m2/day, administered by either subcutaneous injection (strongly recommended) or intravenous infusion over 2 hours.

2.Dinutuximab: 17.5 mg/m2/day, administered by intravenous infusion over 10–20 hours.

3.Isotretinoin: for body weight greater than 12 kg: 80 mg/m2 administered orally twice daily for a total dose of

160 mg/m2/day; for body weight up to 12 kg: 2.67 mg/kg administered orally twice daily for a total daily dose of 5.33 mg/kg/day (round dose up to nearest 10 mg).

Table 7: Courses 2 and 4 dosing schedule for Unituxin and IL-2; Courses 2, 4, and 6 dosing schedule for isotretinoin

Day

1 2 3 4

5 6 7 8

11 12-14 15-28

IL-21

X X X X

X X

X

X

Dinutuximab2

 

X

X

X

X

Isotretinoin3

 

 

 

 

X

1.Interleukin-2 (IL-2): 3 MIU/m2/day administered by continuous intravenous infusion over 96 hours on Days 1-4 and4.5 MIU/m2/day on Days 8-11.

2.Dinutuximab: 17.5 mg/m2/day, administered by intravenous infusion over 10-20 hours.

3.Isotretinoin: for body weight greater than 12 kg: 80 mg/m2 administered orally twice daily for a total dose of

160mg/m2/day; for body weight up to 12 kg: 2.67 mg/kg administered orally twice daily for a total daily dose of 5.33 mg/kg/day (round dose up to nearest 10 mg).

Prior to starting each treatment course, refer to Table 3 for a list of criteria that must be evaluated.

Table 8: Clinical criteria that must be evaluated prior to the start of each treatment course of Unituxin

Central nervous system (CNS) toxicity

Delay course initiation until CNS toxicity is Grade 1 or resolved and/or seizure disorder is well controlled

Hepatic dysfunction

Delay initiation of first course until alanine aminotransferase (ALT) less than 5 times upper limit of

 

normal (ULN). Delay initiation of courses 2-6 until ALT is less than 10 times ULN.

 

 

 

authorised

Thrombocytopenia

 

 

 

Delay course initiation until platelet count is at least 20,000/μL.

If patient has CNS metastases, delay course initiation a

d give platelet transfusion to maintain platelet

 

count at least 50,000/μL.

longer

 

Respiratory dysfunction

 

 

 

Delay course initiation until dyspnoea at rest has been resolved and/or peripheral oxygen saturation is

at least 94 % on room air.

 

 

no

 

 

 

Renal dysfunction

 

 

 

Delay course initiation until creatinine clearance or glomerular filtration rate (GFR) is at least

70 mL/min/1.73 m2

 

product

 

Systemic infection or sepsis

 

 

 

Delay course initiation unt

systemic infection or sepsis has resolved.

Medicinal

 

 

Leukopaenia

Delay initiation of first course until absolute phagocyte count (APC) is at least 1,000/μL.

In addition to the above criteria, clinician judgement must be exercised in the evaluation of the patient’s cardiovascular functions.

Dose modification

Table 4 provides dose modification guidance for dinutuximab, GM-CSF and IL-2. If patients meet criteria for discontinuation of these medications, treatment may continue with isotretinoin as clinically indicated.

Table 9: Dose modification guidance for the management of treatment-emergent adverse reactions during administration of dinutuximab in combination with GM-CSF, IL-2 and isotretinoin.

Allergic reactions

Grade 1 or 2

Onset of symptoms

Reduce rate of infusion to 0.875 mg/m2/h.

 

Administer supportive measures.

After resolution

Resume infusion at the original rate. If not tolerated, reduce rate to

 

 

0.875 mg/m2/h.

Grade 3 or 4

Onset of symptoms

 

Immediately discontinue dinutuximab and intravenous GM-CSF or IL-2.

 

 

Administer supportive measures.

 

 

After resolution

 

If signs and symptoms resolve rapidly with the above measures,

 

 

 

dinutuximab infusion may be resumed at a rate of 0.875 mg/m2/h.

 

 

Do not resume GM-CSF or IL-2 until the following day.

 

 

For GM-CSF courses, administer GM-CSF at 50 % of the dose starting

 

 

 

the next day, and if tolerated, GM-CSF may be given at full dose after

 

 

 

completing dinutuximab dosing for that course.

 

 

For IL-2 courses, administer IL-2 at 50 % of the dose starting the next day

 

 

 

and continue for the remainder of the course.

 

 

 

If symptoms recur with the addition of GM-CSF or IL-2 discontinue GM-

 

 

 

CSF or IL-2 and dinutuximab.

 

 

 

 

If symptoms resolve the following day, resume dinutuximab at tolerated

 

 

 

rate without GM-CSF or IL-2.

 

 

Recurrence

 

Discontinue dinutuximab and GM-CSF or IL-2 for that day.

 

 

If symptoms resolve that day, resume the next day with premedication in

 

 

 

the intensive care setting.

 

 

Subsequent courses

 

Maintain tolerated dinutuximab infusion rate for all subsequent courses

 

 

 

with GM-CSF or IL-2.

 

 

Anaphylaxis

 

 

 

 

 

 

 

 

Grade 3 or 4

 

 

 

 

 

 

 

 

 

 

Permanently discontinue dinutuxim b and GM-CSF or IL-2.

 

 

 

 

 

 

authorised

Capillary leak syndrome

 

 

 

 

 

 

Grade 3 (severe)

 

 

 

 

 

 

 

 

Onset of symptoms

 

Discontinue dinutuximab a d intravenous GM-CSF or IL-2.

 

 

Administer supportive measures.

 

 

 

 

 

 

 

 

longer

 

 

After resolution

 

 

 

 

 

 

 

Resume dinutuximab infusion at 0.875 mg/m /h.

 

 

Resume GM-CSF or IL-2 the following day at 50 % of the dose until the

 

 

 

 

 

no

 

 

 

 

 

 

last dose of dinutuximab for that course.

 

Subsequent courses

 

If patient tolerated 50 % dose of GM-CSF or IL-2, start at this dose and

 

 

 

dinutuximab rate of 0.875 mg/m2/h. If tolerated, increase GM-CSF or

 

 

 

IL-2 to full dose the next day.

 

 

 

 

 

 

product

 

 

 

 

 

 

If GM-CSF is not tolerated at 50 % of the dose, administer dinutuximab

 

 

 

alone for the remainder of the GM-CSF courses.

 

 

If IL-2 is not tolerated at 50 % of the dose, substitute with GM-CSF for

 

 

 

the remainder of the IL-2 courses.

 

Grade 4(life-threatening)

 

 

 

 

 

 

 

Onset of symptoms

 

Discontinue dinutuximab and GM-CSF or IL-2 for that course.

 

Medicinal

 

 

 

 

 

 

 

Administer supportive measures.

 

 

Subsequent courses

 

If capillary leak syndrome occurred during IL-2 course, substitute

 

 

 

GM-CSF for remainder of IL-2 courses.

 

 

 

If capillary leak syndrome occurred during GM-CSF course, administer

 

 

 

dinutuximab alone for subsequent GM-CSF courses.

Hyponatraemia

Grade 4(life-threatening) - < 120 mmol/L despite appropriate fluid management

Permanently discontinue dinutuximab and GM-CSF or IL-2.

Hypotension

Symptomatic and/or systolic BP less than 70 mmHg or a decrease that is more than 15% below baseline

Onset of symptoms

Discontinue dinutuximab and intravenous GM-CSF or IL-2.

 

Administer supportive measures.

After resolution

Resume dinutuximab infusion at 0.875 mg/m2/h.

 

If blood pressure (BP) remains stable for at least 2 hours, resume GM-

 

 

CSF or IL-2.

 

If BP remains stable for at least 2 hours after resuming GM-CSF or IL-2,

 

 

 

increase the dinutuximab infusion to 1.75 mg/m2/h.

Recurrence

 

Discontinue dinutuximab and GM-CSF or IL-2.

 

 

• Resume dinutuximab at 0.875 mg/m2/h once BP is stable.

After resolution

 

Resume GM-CSF or IL-2 the following day at 50 % of the dose if BP

 

 

 

remains stable.

 

 

 

 

• Start GM-CSF or IL-2 at 50 % of the dose when administered with

 

 

 

dinutuximab. Then increase to full dose if tolerated for the remainder of

 

 

 

the course.

 

 

 

 

• If GM-CSF is not tolerated at 50 % of the dose, administer dinutuximab

 

 

 

alone for the remainder of the course.

 

 

• If IL-2 is not tolerated at 50 % of the dose, administer dinutuximab alone

 

 

 

for the remainder of the course.

Subsequent courses

 

Start GM-CSF or IL-2 at 50 % of the dose, increase to full dose if

 

 

 

tolerated the next day.

 

 

• If GM-CSF is not tolerated at 50 % of the dose, administer dinutuximab

 

 

 

alone for the remainder of the GM-CSF courses.

Subsequent courses

 

• If IL-2 is not tolerated at 50 % of the dose, substitute with GM-CSF for

 

If abnormalities remain stable or improveauthorisedbefore the next course

 

 

 

remainder of the IL-2 courses.

Neurological disorders of the eye

 

 

 

Dilated pupil with sluggish light reflex

 

 

 

Onset of symptoms

 

Discontinue dinutuximab and GM-CSF IL-2.

After resolution

 

Administer dinutuximab at 0.875 mg/m2/h and resume GM-CSF or IL-2.

Recurrence

 

Discontinue dinutuximab, GM-CSF, and IL-2 for remaining courses.

 

 

 

 

 

 

longer

 

 

administer dinutuximab at 0.875 mg/m2/h and full dose GM-CSF or IL-2.

 

 

If tolerated without worse i symptoms, administer dinutuximab at

 

 

 

1.75 mg/m2/h for subsequent courses.

 

 

 

 

 

no

 

 

 

• If symptoms recur, discontinue dinutuximab, GM-CSF, and IL-2 for

 

 

 

remaining courses.

 

Grade 3 or 4

 

 

 

product

 

 

Serum sickness

 

 

 

 

 

 

Grade 4 (life-threatening)

 

 

 

 

 

 

Permanently iscontinue dinutuximab and GM-CSF or IL-2.

Systemic infection or sepsis

 

 

 

 

 

 

 

 

 

Grade 4

Medicinal

 

 

 

Onset of symptoms

 

Discontinue dinutuximab and GM-CSF or IL-2 for remainder of course.

After resolution

 

Proceed with subsequent planned dinutuximab and GM-CSF or IL-2

 

 

 

courses.

 

 

Pain

 

 

 

 

 

 

 

 

 

 

 

• Discontinue dinutuximab and GM-CSF or IL-2.

Peripheral neuropathy

 

 

 

 

Grade 2 peripheral motor neuropathy

 

 

 

 

 

• Permanently discontinue dinutuximab and GM-CSF or IL-2.

Grade 3 (sensory changes for more than 2 weeks, objective motor weakness) or Grade 4

 

 

• Discontinue dinutuximab and GM-CSF or IL-2.

Atypical Haemolytic Uraemic Syndrome

 

 

 

 

• Permanently discontinue dinutuximab and GM-CSF or IL-2.

Paediatric population

 

 

 

 

 

 

The safety and efficacy of Unituxin in children aged less than 12 months have not yet been established.

Method of administration

Unituxin should not be administered as an intravenous push or bolus. It should be administered by intravenous infusion over 10 hours. The infusion is started at a dose rate of 0.875 mg/m2/h and continued at this rate for 30 minutes; the rate is then increased to 1.75 mg/m2/h and continued at this rate for the remainder of the infusion, if tolerated. The infusion duration may be extended up to 20 hours to help minimise reactions during infusion that do not respond adequately to other supportive measures. The infusion must be terminated after 20 hours, even if the full dose cannot be delivered within this timeframe.

Pre-medication should always be considered before starting each infusion.

For instructions on dilution of the medicinal product before administration see section 6.6 of the SmPC.

Contraindications

Hypersensitivity (Grade 4) to the active substance or to any of the excipients listed in section 6.1 of the SmPC.

Special warnings and precautions for use

authorised

of the Unituxin infusion.

Allergic reactions

 

Antihistamine premedication (e.g. hydroxyzine or diphenhydramine) should be administered by intravenous injection approximately 20 minutes before starting each dinutuximab infusi n. It recommended that antihistamine medicinal product be repeated every 4–6 hours as required during infusion of Unituxin. Patients should be monitored for signs and symptoms of infusion reactions for 4 hours after the completion

Epinephrine (adrenaline) and hydrocortisone for intravenous administration should be immediately available

at the bedside during administration of dinutuximab to manage life-threatening allergic reactions. It is

recommended that treatment for such reactions include hydrocortisonelonger

administered by intravenous bolus,

 

 

no

 

and epinephrine administered by intravenous bolus o ce every 3–5 minutes as necessary according to

clinical response.

product

 

 

 

 

 

Depending on the severity of the allergic reaction, the rate of infusion should be reduced or treatment discontinued.

Capillary leak syndromeMedicinal

Capillary leak syndrome is more kely when dinutuximab is co-administered with IL-2. It is recommended to administer oral metolazone or intravenous furosemide every 6–12 hours as required. Supplemental oxygen, respiratory support, and albumin replacement therapy should be used as necessary according to clinical response.

Characteristic symptoms and signs include hypotension, generalized oedema, ascites, dyspnoea, pulmonary oedema and acute renal failure associated with hypoalbuminaemia and haemoconcentration.

Pain

Severe pain (Grade 3 or 4) occurs most frequently during the first 4-day course of dinutuximab, often subsiding over time with subsequent courses.

For severe pain, the Unituxin infusion rate should be decreased to 0.875 mg/m2/hour. Unituxin should be discontinued if pain is not adequately controlled despite infusion rate reduction and institution of maximum supportive measures.

Paracetamol should be administered orally 20 minutes prior to starting each dinutuximab infusion, and repeated every 4-6 hours as needed. Regular dosing every 4–6 hours is recommended when IL-2 is coadministered. If required for persistent pain, ibuprofen should be administered orally every 6 hours between doses of paracetamol. Ibuprofen should not be administered if there is evidence of thrombocytopenia, bleeding, or renal dysfunction.

An opioid, such as morphine sulphate, is recommended to be administered by intravenous infusion prior to each dinutuximab infusion and continued as an intravenous infusion during and until 2 hours after completion of the treatment. It is recommended that additional intravenous bolus doses of an opioid are administered as needed for treatment of pain up to once every 2 hours during the dinutuximab infusion. If morphine is not tolerated, then fentanyl or hydromorphone may be utilised.

Lidocaine may be administered as an intravenous infusion (2 mg/kg in 50 mL of 0.9 % sodium chloride) over 30 minutes prior to the start of each dinutuximab infusion and continued via intravenous infusion at

1 mg/kg/h up to 2 hours after completion of the treatment. Lidocaine infusion should be discontinued if the patient develops dizziness, perioral numbness, or tinnitus.

Gabapentin may be administered at the time of starting morphine premedication, at an oral dose of 10 mg/kg/day. The dose may be subsequently increased (up to a maximum of 60 mg/kg/day or 3600 mg/day) as needed for pain management.

Hypotension

authorised

Intravenous sodium chloride 9 mg/mL (0.9%) solution for injection (10 mL/kg) should be administered over

one hour just prior to the dinutuximab infusion. If hypotension occurs, this can be

peated, or intravenous

albumin or packed red blood cells can be administered as clinically indicated. It

recommended that

vasopressor therapy is also administered if necessary to restore an adequate perfusion pressure.

Neurological disorders of the eye

Eye disorders may occur, especially with repeated courses. These ch nges usually resolve over time. Patients should have an ophthalmic examination before initiating therapy and be monitored for visual changes.

Hepatic dysfunction

 

no

longer

Regular monitoring of liver function is recommended during dinutuximab immunotherapy.

Systemic infections

product

 

 

 

 

 

Patients typically have a central venous catheter in situ and as a consequence of prior ASCT are likely to be immunocompromised during therapy, and therefore, at risk of developing systemic infection. Patients

should have no evidence of systemic infection and any identified infection should be under control before

beginning therapy.

Medicinal

 

Laboratory test abnormalities

Electrolyte abnormalities have been reported in patients who received Unituxin. Electrolytes should be monitored daily during therapy with Unituxin.

Atypical Haemolytic Uraemic Syndrome

Haemolytic uraemic syndrome in the absence of documented infection and resulting in renal insufficiency, electrolyte abnormalities, anaemia, and hypertension has been reported. Supportive measures should be instituted including control of hydration status, electrolyte abnormalities, hypertension, and anaemia.

Sodium intake

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

Comments

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
  • Help
  • Get it on Google Play
  • About
  • Info on site by:

  • Presented by RXed.eu

  • 27558

    prescription drugs listed