Defibrotide

Defibrotide is used for adults and children with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT).

Defibrotide is available under the following different brand names: Defitelio.

Dosages of Defibrotide:

Adult and Pediatric Dosage Forms and Strengths

Intravenous (IV) solution

• 200 mg/2.5mL (80mg/mL) vial

Dosage Considerations – Should be Given as Follows:

Hepatic Veno-Occlusive Disease

• Indicated for adults and children with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem cell transplantation (HSCT)
• 6.25 mg/kg IV every 6 hours infused over 2 hours
• Administer for a minimum of 21 days; if after 21 days signs and symptoms of hepatic VOD have not resolved, continue defibrotide until VOD resolution or up to a maximum of 60 days

Severe or life-threatening anaphylaxis: Discontinue permanently; do not resume treatment

Bleeding

• Persistent, severe, or potentially life-threatening
  • Withhold defibrotide
  • Treat the cause of bleeding and give supportive care as clinically indicated
  • Consider resuming treatment (at the same dose and infusion volume) when bleeding has stopped and the patient is hemodynamically stable
• Recurrent significant bleeding
  • Discontinue permanently; do not resume treatment

Invasive Procedures

• There is no known reversal agent for the profibrinolytic effects of defibrotide
• Discontinue infusion at least 2 hours before an invasive procedure
• Resume treatment after the procedure as soon as any procedure-related risk of bleeding is resolved

Common side effects of Defibrotide include:

• Low blood pressure (hypotension)
• Diarrhea
• Vomiting
• Nausea
• Nosebleed
• Pulmonary alveolar hemorrhage
• Gastrointestinal bleeding
• Sepsis
• Graft-versus-host disease (GVHD)
• Lung infiltration
• Pneumonia
• Pulmonary hemorrhage
• Infection
• Hemorrhage intracranial
• High blood uric acid levels (hyperuricemia)
• Cerebral hemorrhage
• Hypersensitivity reactions

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Severe interactions of defibrotide include:
  • alteplase
  • apixaban
  • argatroban
  • bivalirudin
  • dabigatran
  • dalteparin
  • desirudin
  • edoxaban
  • enoxaparin
  • fondaparinux
  • heparin
  • reteplase
  • rivaroxaban
  • tenecteplase
  • vorapaxar
  • warfarin
• Defibrotide has no listed serious interactions with other drugs.
• Defibrotide has moderate interactions with at least 42different drugs.
• Defibrotide has no listed mild interactions with other drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

• This medication contains Defibrotide. Do not take Defitelio if you are allergic to azficel-T or any ingredients contained in this drug.

Contraindications

• Coadministration with systemic anticoagulant or fibrinolytic therapy
• Known hypersensitivity to defibrotide or any of its excipients

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Defibrotide?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Defibrotide?"

Cautions

• Defibrotide increases the activity of fibrinolytic enzymes in vitro, and it may increase the risk of bleeding in patients with the veno-occlusive disease (VOD); monitor for bleeding
• Do not initiate drugs in patients with active bleeding
• If bleeding occurs, discontinue the drug and treat the underlying cause
• Do not use with systemic anticoagulants or fibrinolytic agents (except for routine maintenance or reopening of central venous lines)
• Hypersensitivity reactions reported and may include rash, urticaria, and angioedema

Pregnancy and Lactation

• There are no available data on defibrotide use in pregnant women. Pregnant women should be advised of the potential risk of miscarriage (based on animal data). When administered to pregnant rabbits during the period of organogenesis at doses that were comparable to the recommended human dose based on body surface area, defibrotide sodium decreased the number of implantations and viable fetuses.
• It is unknown if defibrotide is distributed in human breast milk. Because of the potential for serious adverse reactions, including bleeding in a breastfed infant, breastfeeding is not recommended during treatment with defibrotide.