Post-meeting note of 17 September 2021:
After the September plenary, the PRAC discussed emerging information and decided that a review of the additional data is needed before advice to healthcare professionals and patients could be provided. A decision on the best tool to communicate the findings of the review and any recommended measures will be taken at a later stage.
While the assessment is ongoing, healthcare professionals should continue to follow the current product information for Imbruvica. Patients are reminded not to stop taking Imbruvica or ACE inhibitors without first consulting their healthcare professional and to seek medical advice if they have questions or concerns.
This post-meeting note supersedes the information below.
As part of its advice on safety-related aspects to other European Medicines Agency (EMA) committees, the Pharmacovigilance Risk Assessment Committee (PRAC) discussed at its meeting held from 30 August to 2 September 2021 direct healthcare professional communication (DHPC) containing important safety information for ibrutinib (Imbruvica).
This DHPC aims to inform healthcare professionals about a new safety signal of sudden or cardiac death with ibrutinib when used in combination with rituximab and angiotensin-converting enzyme (ACE) inhibitors. The signal was recognised following a review of the findings of a clinical study.
Ibrutinib is used for treatment of mantle cell lymphoma, chronic lymphocytic leukaemia (CLL) and Waldenström’s macroglobulinaemia.
An interim analysis of the clinical study suggested that the risk of sudden or cardiac death in patients on an ACE inhibitor when entering the study was increased in patients randomised to ibrutinib and rituximab, compared to those randomised to fludarabine, cyclophosphamide and rituximab.
While the PRAC is reviewing the signal, as a precautionary measure, for patients with CLL currently receiving ibrutinib plus rituximab together with an ACE inhibitor, the PRAC advises healthcare professionals to reconsider the treatment strategy.
For patients with CLL on ACE-inhibitors who have not yet started treatment with ibrutinib plus rituximab, the treatment strategy should be reconsidered before commencing ibrutinib.
Patients should not stop taking ibrutinib or ACE inhibitors without first consulting their healthcare professional and should talk to their healthcare professional if they have questions or concerns.
The PRAC will communicate final conclusions and recommendations as soon as the evaluation has been completed.
The DHPC for ibrutinib will be forwarded to EMA’s Committee for Medicinal Products for Human Use (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 EMA’s website and in national registers in EU Member States.