Defibrotide is a drug used to treat hepatic veno-occlusive disease (VOD). VOD is a rare but serious liver disease characterized by stenosis or obstruction of the hepatic veins, resulting in restricted blood return within the liver. This disease is often associated with treatments such as bone marrow transplantation, chemotherapy, or radiotherapy. Currently, defibrotide is not available in China. 

Defibrotide(Defitelio):Clinical Uses, Recommended Dosage, Treatment Effect

This article provides a detailed description of the indications, dosage, side effects, contraindications, and clinical efficacy of defibrotide.

(I) Indications

Defibrotide is indicated for the treatment of hepatic veno-occlusive disease (VOD), also known as sinusoidal venous occlusive syndrome (SOS), in adults and children with renal or pulmonary dysfunction after hematopoietic stem cell transplantation (HSCT).

(II) Dosage

1. Recommended dose

(1) The recommended dose of defibrotide for adults and children is 6.25 mg/kg every 6 hours, administered intravenously for 2 hours. The dose should be based on the patient's baseline weight, which is defined as the patient's weight before the hematopoietic stem cell transplantation (HSCT) preparation program.

(2) Use defibrotide for at least 21 days. If signs and symptoms of VOD do not resolve after 21 days, continue defibrotide until VOD resolves or for a maximum of 60 days.

2. Administration Instructions

(1) Defibrotide must be diluted before infusion.

(2) Before administering defibrotide, confirm that the patient is not experiencing clinically significant bleeding and is hemodynamically stable on no more than one vasopressor.

(3) Administer defibrotide continuously intravenously over 2 hours.

(4) Infuse the diluted defibrotide solution using an infusion set equipped with a 0.2 μm inline filter. Immediately flush the intravenous line (peripheral or central) with 5% dextrose injection, USP, or 0.9% sodium chloride injection, USP, before and after administration.

(5) Do not administer defibrotide and other intravenous medications simultaneously in the same vein.

3. Preparation Instructions

(1) Dilute defibrotide with 5% dextrose injection (USP) or 0.9% sodium chloride injection (USP) to a concentration of 4 mg/mL-20 mg/mL. The diluted solution should be administered within 2 hours.

(2) The vials do not contain antimicrobial preservatives and are for single patient use only. Partially used vials should be discarded. The diluted defibrotide solution should be used within 4 hours if stored at room temperature and within 24 hours if stored under refrigerated conditions. A maximum of four doses of defibrotide solution can be prepared at one time.

(3) Preparation Instructions:

① Determine the dose (mg) and number of defibrotide bottles based on the patient's baseline weight (weight before the hematopoietic stem cell transplant preparation protocol).

② Calculate the required volume of defibrotide, withdraw that volume from the vial, and add it to the infusion bag containing 0.9% sodium chloride injection or 5% dextrose injection. The final concentration is 4 mg/mL-20 mg/mL.

③ Gently mix the infusion solution.

④ If the solution and container permit, the injectable drug should be visually inspected for particulate matter and discoloration before administration. Only transparent solutions without visible particles should be used. Depending on the type and amount of diluent, the color of the diluted solution may vary from colorless to pale yellow.

(III) Applicable population

Adult and pediatric patients. Pregnant and lactating women and elderly patients should use the drug under the guidance of a physician.

(IV) Contraindications

Defibrotide is contraindicated in the following situations:

(1) Concomitant administration of systemic anticoagulant or fibrinolytic therapy.

(2) Known hypersensitivity to defibrotide or any of the excipients.

(V) Side effects

The most common adverse reactions (incidence ≥ 10% and not related to causality) are hypotension, diarrhea, vomiting, nausea, and epistaxis.

(VI) Precautions

1. Bleeding

(1) Defibrotide increases the activity of extracorporeal plasmin and may increase the risk of bleeding in patients with VOD after hematopoietic stem cell transplantation (HSCT); patients with active bleeding should not use defibrotide; monitor patients for signs of bleeding; if bleeding occurs in patients taking defibrotide, defibrotide should be discontinued, the underlying cause should be treated, and supportive care should be provided until the bleeding stops.

(2) Concomitant use of defibrotide and systemic anticoagulant or fibrinolytic therapy (excluding routine maintenance or reopening of central venous lines) may increase the risk of bleeding. Discontinue anticoagulants and fibrinolytic drugs before defibrotide treatment and consider delaying the use of defibrotide until the anticoagulant effect has subsided.

2. Allergic reactions

Allergic reactions have occurred in patients receiving defibrotide. These reactions include rash, urticaria, and angioedema. Pay close attention to patients for allergic reactions, especially those with a history of previous exposure. If a severe allergic reaction occurs, discontinue defibrotide, treat according to standard care, and monitor until symptoms subside.

(VII) Therapeutic Efficacy

A multicenter, randomized, placebo-controlled study found that in patients undergoing liver transplantation, the defibrotide/defibrotide sodium treatment group had a significantly improved 28-day survival rate compared to the placebo group. Furthermore, defibrotide/defibrotide sodium demonstrated a trend toward reduced severity of SOS/VOD, improved liver function, and a reduction in transplant-related complications.

(VIII) Drug Interactions

Antithrombotic Agents

Defibrotide may enhance the pharmacodynamic activity of antithrombotic/fibrinolytic drugs (such as heparin or alteplase). Due to the increased risk of bleeding, concomitant use of defibrotide with antithrombotic or fibrinolytic drugs is contraindicated.

(IX) Storage Conditions

Store at 20°C-25°C; transport at 15°C-30°C is permitted.

[Warm Tips]: Some product instructions change frequently; please refer to the actual product.