Defitelio

Package leaflet: Information for the user

Defitelio 80 mg/mL concentrate for solution for infusion

defibrotide
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor. See section 4.

Contents of this leaflet

1. What Defitelio is and what it is used for
2. What you need to know before Defitelio is administered to you
3. How Defitelio will be administered to you
4. Possible side effects
5. How to store Defitelio
6. Contents of the pack and other information

1. What Defitelio is and what it is used for

Defitelio is a medicine that contains the active substance defibrotide.
Defitelio is used to treat a condition called hepatic veno-occlusive disease,
in which the blood vessels of the liver are damaged and blocked by blood clots. This condition may
be caused by medications given before a stem cell transplant.
Defibrotide works by protecting the cells lining the blood vessels and by preventing or dissolving
blood clots.
This medicine can be used in adults, adolescents, children and infants over 1 month of age.

2. What you should know before being given Defitelio

Do not use Defitelio

• if you are allergic to defibrotide or to any of the other ingredients of this medicine (listed in section 6)
• if you are taking other medicines to dissolve blood clots, such as tissue plasminogen activator.

Warnings and precautions
Talk to your doctor before using Defitelio:

• if you are taking a medicine that increases the risk of bleeding.
• if you have severe bleeding and require a blood transfusion.
• if you are scheduled for surgery.
• if you have circulation problems because your body cannot maintain stable blood pressure.

Children and adolescents
Defitelio is not recommended for children under 1 month of age.
Other medicines and Defitelio
Tell your doctor if you are taking medicines to prevent blood clotting, such as acetylsalicylic acid, heparins, warfarin, dabigatran, rivaroxaban or apixaban, or if you are taking anti-inflammatory drugs (e.g., ibuprofen, naproxen, diclofenac and other non-steroidal anti-inflammatory drugs).
Pregnancy and breastfeeding
Do not use Defitelio during pregnancy unless your condition requires treatment with Defitelio.
If you are sexually active and you or your partner could become pregnant, both of you must use an effective method of contraception during treatment with Defitelio and for 1 week after stopping treatment.
Driving and using machines
Defitelio is not expected to affect your ability to drive or operate machinery.
Defitelio contains sodium
This medicine contains 20.4 mg of sodium (a main component of table salt) per vial. This is equivalent to 1.02% of the maximum recommended daily dietary intake for an adult.

3. How Defitelio will be administered to you

Treatment with Defitelio must be initiated and continuously supervised only by an experienced physician, in a hospital or in a specialized stem cell transplant centre.
It will be slowly injected (over a period of 2 hours) into a vein. This procedure is called "intravenous infusion" or intravenous drip.
You will receive this treatment four times a day for at least 21 days and until your symptoms have resolved.
The recommended dose in children aged between 1 month and 18 years is the same as in adults.
If you forget to take Defitelio
Since this medicine will be administered to you by a doctor or nurse, it is unlikely that a dose will be missed. However, if you think a dose has been missed, inform your doctor or healthcare professional. Do not receive a double dose to make up for the missed dose.
If you have any doubts about the use of this medicine, consult your doctor, nurse or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them. The following side effects have been reported in patients treated with Defitelio.
If you experience any of these side effects, contact your doctor immediately.

Very common (may affect more than 1 in 10 people)

• low blood pressure

Common (may affect up to 1 in 10 people)

• general bleeding
• nosebleed
• brain bleeding
• intestinal bleeding
• vomiting blood
• lung bleeding
• bleeding from the infusion site
• blood in urine
• bleeding from the mouth
• subcutaneous bleeding
• coagulopathy (blood clotting disorder)
• nausea
• vomiting
• diarrhoea
• rash
• itching
• fever

Uncommon (may affect up to 1 in 100 people)

• eye bleeding
• blood in stool
• bleeding at injection site
• localized collection of blood outside blood vessels (haematoma) in the brain
• haemothorax (accumulation of blood in the space between the heart and lungs)
• bruising
• allergic reactions (which may present as skin reactions such as rash)
• severe allergic reaction (which may present as swelling of the hands, face, lips, tongue or throat, and breathing difficulties)

Children and adolescents
Side effects in children (aged 1 month to 18 years) are expected to be similar in type, severity and frequency, and no additional special precautions are required.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor. You may also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Defitelio

Keep this medicine out of the sight and reach of children.
Do not use Defitelio after the expiry date stated on the carton and on the label of the vial after "Exp.". The expiry date refers to the last day of that month.
Store below 25 °C. Do not freeze.
Once diluted for use, the infusion must not be stored for more than 24 hours at 2 °C - 8 °C, unless the dilution was carried out under controlled and validated aseptic conditions.
Defitelio must not be used if the solution is cloudy or contains particles.
Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Defitelio contains

• The active substance is defibrotide. Each 2.5 mL vial contains 200 mg of defibrotide and each mL of solution contains 80 mg of defibrotide.
• The other components are sodium citrate dihydrate, hydrochloric acid and sodium hydroxide (both used for pH adjustment), and water for injections (see section 2, “Defitelio contains sodium”).

Description of the appearance of Defitelio and contents of the pack
Defitelio is a clear concentrate for solution for infusion (sterile concentrate), ranging in colour from light yellow to brown, free from particulate matter or turbidity.
One carton contains 10 glass vials, each containing 2.5 mL of concentrate.

Marketing Authorisation Holder and Manufacturer
Gentium S.r.l
Piazza XX Settembre, 2
22079 Villa Guardia (Como)
Italy

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

AT – BE – BG – CY – CZ – DE – DK – EE – EL – ES – FI – FR – HR – HU – IE –
IS – IT – LT – LU – LV – MT – NL – NO – PL – PT – RO – SE – SK – SL

Jazz Pharmaceuticals Ireland Limited
Tel: +353 1 968 1631
(local telephone number in the Republic of Ireland)
(international call rates may apply outside the Republic of Ireland)
E-mail: [email protected]

This medicinal product has been authorised under “exceptional circumstances”. This means that, due to the rarity of the disease and for ethical reasons precluding the use of placebo-controlled clinical trials, complete information on this medicinal product could not be obtained.
The European Medicines Agency will review any new information on this medicinal product annually, and this package leaflet will be updated if necessary.
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.
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