去纤苷/去纤苷钠适应症,功效,用量,副作用,注意事项,价格

Drug ingredients

DEFITELIO (Defibroside/Defibroside Sodium) Injection is a clear, light yellow to brown, sterile, preservative-free solution in single-patient vials for intravenous administration. Each milliliter of injection solution contains 80 mg defibrotide sodium and 10 mg sodium citrate (US Pharmacopeia) in Water for Injection (US Pharmacopeia).

Marketing information

It was approved for medical use in the European Union in October 2013, the United States in March 2016, and Australia in July 2020. It is suitable for the treatment of hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS).

Mechanism of action

Defibrotide is a complex mixture of single-chain polydeoxyribonucleotides derived from porcine intestinal mucosa. It has anti-thrombotic and fibrinolytic activities. In vitro, defibrotide/defibrotide sodium can enhance the enzymatic activity of plasmin to hydrolyze fibrin clots.

Indications

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

Efficacy and effects

1. Anti-thrombotic effect: Defibrotide can reduce the expression of cell adhesion molecules on the surface of endothelial cells, thereby reducing the adhesion of leukocytes to vascular endothelial cells and reducing the inflammatory damage of endothelial cells. At the same time, defibrotide can also promote the release of prostaglandin 12 and prostaglandin E2, thereby causing blood vessel dilation, inhibiting platelet aggregation, and reducing ischemic damage.

2. Promote fibrinolysis: Defibrinoside can reduce EC activation and increase EC-mediated fibrinolysis.

Dosage

Adult and pediatric patients are dosed at 6.25 mg/kg every 6 hours as a 2-hour intravenous infusion for at least 21 days.

Preparing for administration

1. Determine the dose of defibrotide based on the individual patient’s baseline weight.

2. Calculate the required volume of defibrotide, take this amount from the vial, and add it to the infusion bag containing 0.9% sodium chloride injection or 5% glucose injection for each dose, so that the final concentration is 4-20 mg/mL.

3. Gently mix the infusion solution.

4. Injectable drugs should be visually inspected for particulate matter and discoloration before administration, and only transparent solutions without visible particles should be used.

Side effects

The most common are hypotension, diarrhea, vomiting, nausea and epistaxis. Other side effects mainly include alveolar hemorrhage, gastrointestinal bleeding, sepsis, graft-versus-host disease, pulmonary infiltration, pneumonia, pulmonary hemorrhage, intracranial hemorrhage, hyperuricemia, etc.

Common side effects treatment measures

1. Hypotension: You can stop taking defibrinoside as directed by your doctor, adjust your diet, eat high-salt foods to increase blood volume, and avoid strenuous exercise and prolonged standing to reduce the risk of blood pressure drop.

2. Diarrhea: Drink more water to replenish fluids to prevent dehydration, adjust your diet, and avoid spicy, greasy, cold, and irritating foods, such as peppers, fatty meats, ice cream, etc.

3. Vomiting and nausea: Avoid strenuous exercise and replenish water to prevent dehydration caused by vomiting. Choose light and easy-to-digest foods, such as porridge, noodles, etc.

4. Epistaxis: Keep the nasal cavity clean and avoid pinching and rubbing the nose. You can apply ice packs near the nose and cheeks to help stop bleeding.

Precautions

1. Bleeding: During medication, patients should be monitored for signs of bleeding. If a patient receiving defibrotide treatment develops bleeding, defibrotide treatment should be stopped, and the underlying cause should be treated and supportive treatment provided until the bleeding stops.

2. Allergic reactions: Patients should be monitored for allergic reactions during treatment, especially those with a history of previous exposure. If a severe allergic reaction occurs, discontinue treatment with defibrotide and treat according to standard of care and monitor until symptoms resolve.

Price

It is understood that the defibrotide produced by Jazz Pharmaceuticals, an Irish biopharmaceutical company, is relatively expensive. The current reference price is about $38,500 per box. Moreover, it cannot be purchased in China and needs to be purchased abroad or obtained through domestic overseas medical service institutions.

Clinical research

To determine the safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF, a phase 3 study compared patients taking 25 mg/kg of defibrotide daily (n=102) with 32 controls from a pool of 6867 HSCT patients.

The observed rate in the defibrotide group was 38.2%, compared with 25% in the control group. The observed +100-day complete remission (CR) rate in the defibrotide group was 25.5%, compared with 12.5% ​​in the control group.

Contraindications

1. Concomitant administration with systemic anticoagulation or fibrinolytic therapy is contraindicated.

2. It is prohibited for those who are known to be allergic to defibrotide or any of its excipients.

Save

Defibrotide should be stored at 20°C-25°C (68°F-77°F), with a tolerance of 15°C-30°C (59°F to 86°F). Diluted defibrotide solutions should be used within 4 hours if stored at room temperature and within 24 hours if stored under refrigerated conditions.

References:

Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, Arai S, Grupp SA, Guinan EC, Martin PL, Steinbach G, Krishnan A, Nemecek ER, Giralt S, Rodriguez T, Duerst R, Doyle J, Antin JH, Smith A, Lehmann L, Champlin R, Gillio A, Bajwa R, D'Agostino RB Sr, Massaro J, Warren D, Miloslavsky M, Hume RL, Iacobelli M, Nejadnik B, Hannah AL, Soiffer RJ. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016 Mar 31;127(13):1656-65. doi: 10.1182/blood-2015-10-676924. Epub 2016 Jan 29. PMID: 26825712; PMCID: PMC4817309.

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