Silver Spring, MD (Press Release) – On March 30, 2016, the U. S. Food and Drug Admin­istra­tion approved Defitelio (defibrotide sodium, Jazz Pharma­ceu­ticals, Inc.) for the treat­ment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syn­drome, with renal or pul­monary dysfunction fol­low­ing hematopoietic stem-cell trans­plan­ta­tion (HSCT).

The efficacy of defibrotide sodium was in­ves­ti­gated in 528 patients treated on three studies: two prospective clin­i­cal trials and an expanded access study. The patients enrolled had a diag­nosis of hepatic VOD with multi-organ dysfunction after trans­plan­ta­tion. They received defibrotide sodium 6.25 mg/kg in­tra­venously every 6 hours until resolution of VOD.

The approval was based on survival at Day +100 after HSCT. The Day +100 survival rates for Study 1, Study 2 and Study 3 were 38% (95% CI: 29%, 48%), 44% (95% CI: 33%, 55%) and 45% (95% CI: 40%, 51%) re­spec­tive­ly. Based on published reports and analyses of patient-level data, the Day + 100 survival rates were 21% to 31% for patients with hepatic VOD with renal or pul­mo­nary dysfunction who received sup­port­ive care or interventions other than defibrotide sodium.

In vitro defibrotide sodium has profibrinolytic activity. The use of defibrotide sodium is contraindicated in patients being treated concurrently with anticoagulants or fibrinolytic ther­a­pies. Hemorrhage and hyper­sensitivity reac­tions are the major poten­tial adverse reac­tions. The most common adverse reac­tions (incidence greater than or equal to 10%) were hypo­­tension, diarrhea, vomiting, nausea, and epistaxis.

The recommended dose and schedule for defibrotide sodium is 6.25 mg/kg in­tra­venously every 6 hours given as a 2-hour infusion for at least 21 days, and con­tinued until VOD resolution or up to 60 days of treat­ment.

This appli­ca­tion was granted Priority Review. A description of expedited pro­grams is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, avail­able at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Full pre­scrib­ing in­­for­ma­tion is avail­able at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208114lbl.pdf

Healthcare professionals should report all serious adverse events sus­pected to be asso­ci­ated with the use of any medicine and device to FDA’s MedWatch Reporting System by com­plet­ing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Source: Food and Drug Admin­istra­tion.