PRAC May 2022 – Discussion regarding a direct healthcare professional communication (DHPC) containing important information for Defitelio

date: 13/05/2022

During its April 2022 meeting, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) discussed a direct healthcare professional communication (DHPC) containing important information for Defitelio. 

This DHPC informs healthcare professionals about the result of a study which compared Defitelio (defibrotide) in combination with best supportive care (BSC) with BSC alone, when used for prophylaxis (prevention of) veno-occlusive disease (VOD) after hematopoietic stem-cell transplantation (HSCT). Prophylaxis of VOD is not an authorised indication for Defitelio.

VOD is a rare condition in which the veins in the liver become blocked and stop the liver working properly. VOD is usually a complication resulting from a treatment known as myeloablative chemotherapy given before HSCT. Defitelio is authorised to treat severe VOD in patients undergoing HSCT, in adults and in children from one month of age.

Results from a Phase 3, randomised, adaptive study (Study 15-007) conducted in 372 adult and paediatric patients, have been reviewed. The study was stopped after interim analysis as it showed that there is no benefit in using Defitelio for prevention of severe VOD after HSCT.

The most common side effects with Defitelio are hypotension (low blood pressure) and bleeding. Defitelio increases the risk of bleeding and should be withheld or stopped if significant bleeding occurs.

EMA’s human medicines committee, the CHMP, concluded on the need to communicate to health care professionals about these findings, which is supported by the PRAC. The PRAC has provided advice on the proposed DHPC. In view of the findings of the study and taking the safety profile of defibrotide into account, the PRAC considers it useful to inform health care professionals that Defitelio should not be used for prophylactic treatment of VOD.

The DHPC for Defitelio will be forwarded to the CHMP. Following the CHMP decision, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holder, according to an agreed communication plan, and published on the Direct healthcare professional communications page and in national registers in EU Member States.

Defitelio is commercialised in Belgium.

More information is available on the EMA website

Last updated on 13/05/2022