Defibrotide
Mechanism :
In addition, defibrotide protects endothelial cells from damage caused by chemotherapy, tumor necrosis factor alpha, serum starvation, and perfusion.
Defibrotide acts by increasing expression of tissue plasminogen activator (tpa) and thrombomodulin. Also reduces expression of von willebrand factor (vWF) and plasminogen activator inhibitor-1. Hence increases fibrinolysis and breaks down clots in blood. By enhancing enzymatic activity of plasmin to hydrolyze fibrin clots.
Indication :
- Treatment of adults and kids with hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS) with kidney or pulmonary dysfunction after hematopoietic stem cell transplantation (HSCT)
Contraindications :
Hypersensensitivity to the drug or its components.
If the patient is hemodynamically unstable.
Severe or nearly fatal anaphylaxis: Discontinue the drug permanently and do not resume therapy.
Hemorrhage:
• Persistent, severe, or nearly fatal bleeding:
o Stop defibrotide infusion immediately
o Treat the underlying cause of hemorrhage and provide supportive care as clinically indicated
o Consider resuming therapy (at the same dose and infusion volume) when there is cessation of hemorrhage and the patient is hemo-dynamically stable
• Recurrent significant hemorrhage: Discontinue the drug permanently and do not resume therapy.
Invasive procedures:
• Unfortunately, there is no known reversal agent for the pro-fibrinolytic effects of defibrotide
• Stop infusion at least 2 hours before an invasive procedure
• Resume therapy after the procedure, as soon as any procedure-related risk of hemorrhage is resolved
Dosing :
Available as 200 mg/2.5 mL (80 mg/mL) vials for intravenous administration.
In Hepatic Veno-Occlusive Disease, 6.25 mg/kg via intravenous route must be infused over 2 hours, every 6 hours.
Administer for at least 21 days; if by then, clinical symptoms of hepatic VOD have not resolved, continue the drug until resolution or until a maximum of 60 days.
Dosing is based on weight of the patient before preparative regimen for HSCT. No dose adjustment for pediatric population.
Adverse Effect :
>10%: Low blood pressure, diarrhea, emesis, nausea, nasal bleeding
1-10%: Pulmonary alveolar hemorrhage, sepsis, graft versus host disease, gastrointestinal bleeding, lung infiltration, consolidation of lung, pulmonary hemorrhage, infection, intracranial bleeding, hyperuricemia, cerebral hemorrhage, allergic reaction.
Interaction :
No known serious interactions with other drugs
Lactation :
It is not known if the drug is distributed in milk during lactation. However, due to possible risk of hemorrhage in infants, lactating women are advised not to breastfeed their infants during therapy. Prior to administration of the drug in lactating women, consider the risks of neonatal drug exposure, risk of an untreated condition and benefits of breast-feeding.
Pregnanacy :
No available human data on use in pregnancy. In animal reproduction studies, defibrotide was found to reduce the number of implantations and viable fetuses. Pregnant females must be advised about the risk of miscarriage as suggested by animal data.