Janssen Updates Warnings Section of Imbruvica Label

Janssen has updated the warnings and precautions section of the label of Imbruvica (ibrutinib) to include information about the possibility of cardiac failure and sudden death.

Imbruvica is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech and Pharmacyclics, an AbbVie company, and used to treat patients with B-cell blood cancers.

A Janssen spokesperson said the update was made to further characterize the uncommon risk of potential cardiac events and provide more specific guidance related to dose modifications for patients receiving therapy. “We continually monitor patient safety and, working closely with the FDA, update our label guidance accordingly as additional clinical trial data and real-world experience are accumulated,” the spokesperson said.

Imbruvica blocks the Bruton's tyrosine kinase (BTK) protein, which is needed by normal and abnormal B-cells, including specific cancer cells, to multiply and spread. By blocking BTK, Imbruvica may help inhibit their proliferation.

The FDA first approved Imbruvica in November 2013, and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include indications to treat adults with CLL/SLL with or without 17p deletion (del17p), and adults with Waldenström’s macroglobulinemia (WM), and adult patients with previously treated mantle cell lymphoma (MCL), as well as to treat adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy, and adult patients with previously treated chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.

“We are confident in the benefit/risk profile of Imbruvica, which has been used to treat more than 250,000 patients worldwide with B-cell blood cancers,” the spokesperson said. “Imbruvica is the most comprehensively studied and prescribed medicine in its class and is the only BTKi with 11 approvals across 6 indications, including five hematologic cancers and chronic graft-versus-host disease.”

The warnings and precautions section now reads (changes are underlined):

“Fatal and serious cardiac arrhythmias and cardiac failure have occurred with Imbruvica. Deaths due to cardiac causes or sudden deaths occurred in 1% of 4,896 patients who received Imbruvica in clinical trials, including in patients who received Imbruvica in unapproved monotherapy or combination regimens. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Patients with cardiac comorbidities may be at greater risk of these events.

“Grade 3 or greater 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 greater cardiac failure was reported in 1.3% of 4,896 patients who received Imbruvica in clinical trials, including in patients who received Imbruvica in unapproved monotherapy or combination regimens.

“These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections.

“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 Imbruvica treatment.”