Presentation and Status in Health Basket
10 X 200 mg / 2.5 ml
The recommended dose is 6.25 mg/kg body weight every 6 hours (25 mg/kg/day).
There is limited efficacy and safety data on doses above this level and consequently it is not recommended to increase the dose above 25 mg/kg/day.
The treatment should be administered for a minimum of 21 days and continued until the symptoms and signs of severe VOD resolve.
Renal impairment: Dose adjustment is not required for patients with renal impairment or who are on intermittent haemodialysis.
Hepatic impairment: No formal pharmacokinetic studies have been performed in patients with hepatic impairment; however, the medicinal product has been used in clinical trials of patients developing hepatic impairment without dose
adjustment with no safety issues identified. No dose adjustment is therefore recommended but careful monitoring of patients should be undertaken.
Paediatric population: The recommended dose for children aged 1 month to 18 years is the same mg/kg dose as for adults i.e. 6.25 mg/kg body weight every 6 hours.
The safety and efficacy of defibrotide in children aged less than 1 month has not yet been established. No data are available. The use of Defitelio® in children aged less than one month is not recommended.
Method of administration: Defitelio® is for intravenous use. It is administered by intravenous infusion, over two hours.
Defitelio® should always be diluted prior to use. It can be diluted with 5% glucose solution for infusion or sodium chloride 9 mg/mL (0.9%) solution for infusion, to a suitable concentration to permit infusion over 2 hours. The total volume of infusion should be determined based on the individual’s patient
weight. The final concentration of Defitelio® should be in the range of 4 mg/mL to 20 mg/mL.
Vials are intended for a single use and unused solution from a single dose must be discarded.
Defitelio® is indicated for the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstructive syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy.
It is indicated in adults and in adolescents, children and infants over 1 month of age.
Hypersensitivity to the active substance or to any of the excipients.
Concomitant use of thrombolytic therapy (e.g. t-PA).
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded in the patient file.
Use of medicinal products that increase the risk of haemorrhage within 24 hours of Defitelio® administration (within 12 hours in the case of unfractionated heparin) is not recommended.
Concomitant systemic anticoagulant therapy (e.g. heparin, warfarin, direct thrombin inhibitors and direct factor Xa inhibitors), except for routine maintenance or reopening of central venous line, requires careful monitoring. Consideration should be given to discontinuation of Defitelio® during use of
Medicinal products that affect platelet aggregation (e.g. non–steroidal anti-inflammatory agents) should be administered with care, under close medical supervision, during Defitelio® administration.
In patients who have or develop clinically significant acute bleeding requiring blood transfusion, Defitelio® is not recommended or should be discontinued. Temporary discontinuation of Defitelio® is recommended in patients who undergo surgery or invasive procedures at significant risk of major bleeding.
Administration of defibrotide to patients who have haemodynamic instability, defined as inability to maintain mean arterial pressure with single pressor support, is not recommended.
A bolus administration of Defitelio® may cause flushing or a sensation of “generalised heat”.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially “sodium-free”.
The most frequent adverse reactions observed during the treatment of hepatic VOD are haemorrhage (including but not limited to gastrointestinal haemorrhage, pulmonary haemorrhage and epistaxis) and hypotension.
In addition, although in the defibrotide studies in VOD there have been no reports of hypersensitivity, cases of hypersensitivity including anaphylaxis were reported from a previously marketed formulation of defibrotide, consequently hypersensitivity is included as an ADR.
See prescribing information for full details.
Potential interactions with recombinant t-PA: In a mouse model of thromboembolism, recombinant t-PA potentiated the antithrombotic effect of
defibrotide when given intravenously and thus co-administration may present an increased risk of haemorrhage and is contraindicated.
Potential interactions with antithrombotic fibrinolytic agents: Defibrotide has a profibrinolytic effect and this may potentially enhance the activity of
antithrombotic/fibrinolytic medicinal products.
There is currently no reported experience in patients on the concomitant treatment with Low Molecular Weight Heparins (LMWHs), warfarin or the concomitant treatment with direct thrombin inhibitors (e.g., dabigatran) or direct Factor Xa inhibitors (e.g., rivaroxaban and apixaban). Therefore, the use of defibrotide with antithrombotic/fibrinolytic medicinal products is not recommended.
However, if used, in exceptional cases, caution should be exercised by closely monitoring the coagulation parameters.
Potential interactions with other medicinal products: Defibrotide does not inhibit or induce CYP450s.
Pregnancy and Lactation
Pregnancy: There are no studies using defibrotide in pregnant women. Embryo-foetal developmental toxicology studies in pregnant rats and rabbits of defibrotide doses close to the recommended therapeutic human dose, revealed
a high rate of haemorrhagic abortion.
Defitelio® should not be used during pregnancy unless the clinical condition of the woman requires treatment with Defitelio®.
Lactation: It is not known whether defibrotide is excreted in human milk. Considering the nature of the medicinal product, a risk to the newborns/infants is not expected. Defitelio® may be used during breastfeeding.
There is no specific antidote for overdose and treatment should be symptomatic. Defibrotide is not removed by dialysis.