Advice for healthcare professionals:
cases of ventricular tachyarrhythmia have been reported
temporarily discontinue ibrutinib in patients who develop symptoms suggestive of ventricular arrhythmia, including palpitations, chest pain, dyspnoea, dizziness, or fainting, and assess benefit-risk before restarting therapy
be aware of the risk of hepatitis B virus reactivation and establish hepatitis B virus status before initiating therapy
for patients with positive hepatitis B serology, consultation with a liver disease expert is recommended before the start of treatment; monitor and manage patients according to local medical standards of care to minimise the risk of hepatitis B virus reactivation
consider prophylaxis according to standard of care for patients who are at an increased risk of opportunistic infections
Routine European review
A routine European review examined the safety profile of ibrutinib. Data from randomised controlled trials and the scientific literature were assessed. Worldwide spontaneous suspected adverse drug reaction (ADR) reports were also reviewed from a cumulative post-marketing exposure of approximately 38,000 patient-years.
Randomised controlled trials reported a slightly increased risk of ventricular tachyarrhythmia with ibrutinib. In a 2017 study of case reports of relevant events from post-marketing sources and clinical trial data, the authors identified 11 cases of ventricular tachycardia/ventricular fibrillation and 6 cases of sudden cardiac death in patients exposed to ibrutinib. In 12 of these 17 cases, the events occurred without any evidence of prior cardiac history.
The review also identified 2 spontaneous ADRs of ventricular tachyarrhythmia in which the role of ibrutinib could not be excluded.
The product information of ibrutinib is being updated to include ventricular tachyarrhythmia as a common adverse reaction (thought to occur in fewer than 10 in 100 patients taking ibrutinib post-marketing).
Temporarily discontinue ibrutinib in patients who develop signs or symptoms of ventricular tachyarrhythmia, including, but not limited to, palpitations, chest pain, dyspnoea, dizziness, or fainting. Perform a complete clinical benefit-risk assessment before possibly restarting therapy.
Hepatitis B virus reactivation
Data for hepatitis B virus reactivation were not available from clinical trials since all patients had been pre-screened for hepatitis B status and those who tested positive were excluded from studies.
The review identified 8 cases of hepatitis B reactivation in which the role of ibrutinib was considered probable or possible.
The product information of ibrutinib is being updated to include hepatitis B virus reactivation as an uncommon adverse reaction (see letter to healthcare professionals).
Establish hepatitis B virus status before initiating treatment with ibrutinib. In patients with positive hepatitis B serology, consultation with a liver disease expert is recommended before starting treatment.
Patients with positive hepatitis B serology who require ibrutinib should be monitored and managed according to local medical standards of care to minimise the risk of hepatitis B virus reactivation.
Infections are a frequent co-morbidity in patients with the haematological malignancies in which ibrutinib is indicated.
The product information for ibrutinib already lists opportunistic infections as very common adverse reactions (thought to affect more than 10 in 100 patients taking the drug post-marketing).
The review identified 157 cases of aspergillosis among patients exposed to ibrutinib in post-marketing settings, 43 of which were fatal. The review also identified 44 cases of Pneumocystis Jirovecii pneumonia (PJP), none of which were fatal. In clinical trials, ibrutinib did not appear to raise the risk of aspergillosis or PJP compared with comparator treatments.
Given the relatively high number of fatal cases, healthcare professionals should consider prophylaxis according to standard of care for all patients who are at an increased risk of opportunistic infections.
Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK), involved in the maturation of B-cells.
Ibrutinib is indicated for the treatment of adult patients with:
- mantle cell lymphoma who have received at least one prior therapy
- chronic lymphocytic leukaemia (CLL), including CLL with deletion 17p
- Waldenstrӧm’s macroglobulinaemia
Call for reporting
This product is subject to additional monitoring. Report any suspected adverse drug reactions associated with ibrutinib to us on a Yellow Card.
Article citation: Drug Safety Update volume 11 issue 1, August 2017: 1