FDA Revises Ibrutinib Label to Reflect Cardiac Risks

The FDA approved certain changes to the label for ibrutinib to include a warning that deaths due to cardiac causes or sudden deaths occurred in 1% of 4,896 patients who received ibrutinib in clinical trials.

Such adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities, although patients with cardiac comorbidities could be at greater risk, the FDA warned.

Grade 3 or more severe ventricular tachyarrhythmias were reported in 0.2%, Grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and Grade 3 or higher cardiac failure was reported in 1.3% of 4,896 patients who received ibrutinib in clinical trials, including patients who received the drug in unapproved monotherapy or combination regimens, the agency explained.

Health care providers are advised by FDA to "Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines … and consider the risks and benefits of continued [ibrutinib] treatment."

In the event of hypertension arising in patients receiving ibrutinib, the revised label calls for health care providers to monitor blood pressure in these patients, initiate or adjust anti-hypertensive medication as appropriate during ibrutinib treatment, and follow dosage modification guidelines for Grade 3 or higher hypertension.

Finally, the label now states that ibrutinib "can cause fetal harm when administered to pregnant women…"

More complete information is available on the updated ibrutinib label.

Ibrutinib is a kinase inhibitor and is used for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia (with or without 17p deletion), chronic graft versus host disease, and Waldenström’s macroglobulinemia, as well as an accelerated approval for certain patients with Marginal zone lymphoma. It initially received FDA approval in 2013.

Ibrutinib is marketed by Pharmacyclics LLC and Janssen Biotech Inc. as Imbruvica.