Defibrotide

The mechanism of action of defibrotide sodium has not been fully elucidated. In vitro , defibrotide sodium enhances the enzymatic activity of plasmin to hydrolyze fibrin clots.

• DEFITELIO is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT). DEFITELIO is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

• The use of DEFITELIO is contraindicated in the following conditions: • Concomitant administration with systemic anticoagulant or fibrinolytic therapy [see Warnings and Precautions (5.1) ] • Known hypersensitivity to DEFITELIO or to any of its excipients [see Warnings and Precautions (5.2) ] • Concomitant administration with systemic anticoagulant or fibrinolytic therapy. ( 4 ) • Known hypersensitivity to DEFITELIO or to any of its excipients.contraindicated

• Administer DEFITELIO 6.25 mg/kg every 6 hours given as a 2-hour intravenous infusion. ( 2.1 ) • Treat for a minimum of 21 days. If after 21 days signs and symptoms of VOD have not resolved, continue treatment until resolution. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of DEFITELIO for adult and pediatric patients is 6.25 mg/kg every 6 hours given as a 2‑hour intravenous infusion. The dose should be based on patient’s baseline body weight, defined as the patient’s weight prior to the preparative regimen for HSCT. Administer DEFITELIO for a minimum of 21 days. If after 21 days signs and symptoms of hepatic VOD have not resolved, continue DEFITELIO until resolution of VOD or up to a maximum of 60 days. 2.2 Administration Instructions • DEFITELIO must be diluted prior to infusion [see Dosage and Administration (2.4) ] . • Prior to administration of DEFITELIO, confirm that the patient is not experiencing clinically significant bleeding and is hemodynamically stable on no more than one vasopressor [see Warnings and Precautions (5.1) ] . • Administer DEFITELIO by constant intravenous infusion over a 2-hour period. • Administer the diluted DEFITELIO solution using an infusion set equipped with a 0.2 micron in-line filter. Flush the intravenous administration line (peripheral or central) with 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP immediately before and after administration. • Do not co‑administer DEFITELIO and other intravenous drugs concurrently within the same intravenous line.

• Hemorrhage: Monitor patients for bleeding. Withhold or discontinue DEFITELIO if significant bleeding occurs. ( 2.3 , 5.1 ) • Hypersensitivity Reactions: If severe or life threatening allergic reaction occurs, discontinue DEFITELIO, treat according to standard of care, and monitor until signs and symptoms resolve. ( 2.3 , 5.2 ) 5.1 Hemorrhage DEFITELIO increased the activity of fibrinolytic enzymes in vitro, and it may increase the risk of bleeding in patients with VOD after hematopoietic stem-cell transplantation (HSCT). Do not initiate DEFITELIO in patients with active bleeding. Monitor patients for signs of bleeding. If patients on DEFITELIO develop bleeding, discontinue DEFITELIO, treat the underlying cause, and provide supportive care until the bleeding has stopped [see Dosage and Administration (2.3) ] . Concomitant use of DEFITELIO and a systemic anticoagulant or fibrinolytic therapy (not including use for routine maintenance or reopening of central venous lines) may increase the risk of bleeding. Discontinue anticoagulants and fibrinolytic agents prior to DEFITELIO treatment, and consider delaying the start of DEFITELIO administration until the effects of the anticoagulant have abated [see Contraindications (4) ] . 5.2 Hypersensitivity Reactions Hypersensitivity reactions have occurred in less than 2% of patients treated with DEFITELIO. These reactions include rash, urticaria and angioedema. One case of an anaphylactic reaction was reported in a patient who had previously received DEFITELIO.

The following adverse reactions are discussed in greater detail in other sections of the labeling: • Hemorrhage [see Warnings and Precautions (5.1) ] • Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] The most common adverse reactions (incidence ≥10% and independent of causality) with DEFITELIO treatment were hypotension, diarrhea, vomiting, nausea, and epistaxis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals, Inc. at 1-800-520-5568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of DEFITELIO was determined in 176 adult and pediatric patients with hepatic VOD with pulmonary and/or renal dysfunction following HSCT who were treated with DEFITELIO 6.25 mg/kg every 6 hours [see Clinical Studies (14) ] . Patients were excluded from these trials if at time of study entry they had significant acute bleeding, active grades B-D graft-versus-host disease, or a requirement for multiple vasopressors to provide blood pressure support. For the purposes of adverse event recording in the clinical trials, events were not required to be reported if they were related to the hepatic VOD, or if they were expected to occur after hematopoietic stem-cell transplantation (HSCT), unless they were serious or Grade 4-5.

8.1 Pregnancy Risk Summary There are no available data on DEFITELIO use in pregnant women. 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. Advise pregnant women of the potential risk of miscarriage. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data Embryo-Fetal toxicity assessment was attempted in rats and rabbits, but was not possible because of high maternal mortality, abortion, and fetal resorption at all doses. Pregnant rats were administered defibrotide sodium from gestational day (GD) 6 to 15 at 0, 240, 1200, and 4800 mg/kg/day by continuous intravenous infusion over 24 hours or at 60, 120, and 240 mg/kg/day by 2-hour infusions 4 times per day. Pregnant rabbits were administered defibrotide sodium at 0, 30, 60, or 120 mg/kg/day from GD 6 to 18 by 2-hour infusions 4 times per day.

Metabolism

Absorption After intravenous administration, peak plasma concentrations of defibrotide sodium occur approximately at the end of each infusion. Distribution Defibrotide sodium is highly bound to human plasma proteins (average 93%) and has a volume of distribution of 8.1 to 9.1 L.

There are no known cases of overdose with DEFITELIO. There is no known antidote for DEFITELIO, and DEFITELIO is not dialyzable. If an overdose occurs, institute general supportive measures.

• Mar 30, 2016NDANDA208114Jazz Pharms Inc

1. 1Off Label Use1,23435%
2. 2Venoocclusive Disease56416%
3. 3Death45213%
4. 4Multiple Organ Dysfunction Syndrome3439.7%
5. 5Venoocclusive Liver Disease3279.3%
6. 6Intentional Product Use Issue1985.6%
7. 7Hypotension1594.5%
8. 8Haemorrhage1544.4%
9. 9Acute Graft Versus Host Disease1383.9%
10. 10Gastrointestinal Haemorrhage1213.4%
11. 11Sepsis1213.4%
12. 12Renal Failure1032.9%
13. 13Septic Shock1032.9%
14. 14Disease Progression962.7%
15. 15Cystitis Haemorrhagic922.6%

The 10 most recently updated of 25 ClinicalTrials.gov registrations naming Defibrotide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Defibrotide for the Treatment of Severe COVID-19
  Recruiting · Phase 2 · Interventional · 42 enrolled · Brigham and Women's Hospital
  NCT04652115updated 2026-05-26
• Defibrotide Dose-escalation for SOS Post-HSCT
  Recruiting · Phase 2 · Interventional · 20 enrolled · New York Medical College
  NCT05987124updated 2026-04-15
• Myeloablative Conditioning, Prophylactic Defibrotide and Haplo AlloSCT for Patients With Sickle Cell Disease
  Recruiting · Phase 2 · Interventional · 40 enrolled · New York Medical College
  NCT02675959updated 2025-05-23
• Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy for Neuroblastoma
  Withdrawn · Phase 2 · Interventional · 0 enrolled · University of California, San Francisco
  NCT06182410updated 2024-08-07
• Sinusoidal Obstruction Syndrome for Stem Cell Transplant Patients Biomarker Study
  Completed · Observational · 80 enrolled · Indiana University
  NCT03132337updated 2023-12-19
• Defibrotide in Sickle Cell Disease-Related Acute Chest Syndrome
  Completed · Phase 2 · Interventional · 20 enrolled · New York Medical College
  NCT03805581updated 2023-12-08
• Defibrotide in Children With High Risk Kawasaki Disease
  Unknown · Phase 2 · Interventional · 2 enrolled · New York Medical College
  NCT04777422updated 2023-10-26
• Defibrotide as Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome of Covid 19.
  Completed · Phase 2 · Interventional · 156 enrolled · Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
  NCT04348383updated 2023-06-07
• Defibrotide Therapy for SARS-CoV2 (COVID-19) Acute Respiratory Distress Syndrome (ARDS)
  Completed · Phase 1 · Interventional · 13 enrolled · Gregory Yanik
  NCT04530604updated 2023-05-09
• Defibrotide in COVID-19 Pneumonia
  Completed · Phase 2 · Interventional · 50 enrolled · IRCCS San Raffaele
  NCT04335201updated 2022-07-19

Frequently asked questions

How does Defibrotide work?

The mechanism of action of defibrotide sodium has not been fully elucidated. In vitro , defibrotide sodium enhances the enzymatic activity of plasmin to hydrolyze fibrin clots.

What is Defibrotide used for?

According to FDA labeling, Defibrotide carries indications including: DEFITELIO is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT). DEFITELIO is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Defibrotide?

Defibrotide is classified as Other antithrombotic agents, Tissue Plasminogen Activators, Increased Fibrinolysis.

What are the brand names for Defibrotide?

Defibrotide is marketed under brand names including Defitelio.

What are the contraindications for Defibrotide?

Defibrotide labeling lists contraindications including: The use of DEFITELIO is contraindicated in the following conditions: • Concomitant administration with systemic anticoagulant or fibrinolytic therapy [see Warnings and Precautions (5.1) ] • Known hypersensitivity to DEFITELIO or to any of its excipients [see Warnings and Precautions (5.2) ] • Concomitant administration with systemic anticoagulant or fibrinolytic therapy. ( 4 ) • Known hypersensitivity to DEFITELIO or to any of its excipients.. Always consult the full prescribing information and a clinician.