IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA .
Major hemorrhage (≥Grade 3, serious, or any central nervous system events; e.g.,
intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding,
hematuria, and post procedural hemorrhage) have occurred in 4% of patients, with
fatalities occurring in 0.4% of 2,838 patients exposed to IMBRUVICA ® in 27 clinical trials.
Bleeding events of any grade, including bruising and petechiae, occurred in 39% of
patients treated with IMBRUVICA ® .
The mechanism for the bleeding events is not well understood.
Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA ®
increases the risk of major hemorrhage. In IMBRUVICA ® clinical trials, 3.1% of patients
taking IMBRUVICA ® without antiplatelet or anticoagulant therapy experienced major
hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy
increased this percentage to 4.4%, and the addition of anticoagulant therapy with or
without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and
benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA ® .
Monitor for signs and symptoms of bleeding.
Consider the benefit-risk of withholding IMBRUVICA ® for at least 3 to 7 days pre- and
post-surgery depending upon the type of surgery and the risk of bleeding.
Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have
occurred with IMBRUVICA ® therapy. Grade 3 or greater infections occurred in 24% of
1,124 patients exposed to IMBRUVICA ® in clinical trials. Cases of progressive multifocal
leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred
in patients treated with IMBRUVICA ® . Consider prophylaxis according to standard of care
in patients who are at increased risk for opportunistic infections.
Monitor and evaluate patients for fever and infections and treat appropriately.
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Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (23%),
thrombocytopenia (8%), and anemia (3%) based on laboratory measurements occurred
in patients with B-cell malignancies treated with single agent IMBRUVICA ® .
Monitor complete blood counts monthly.
Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred with
IMBRUVICA ® therapy. Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2%
of patients, and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4% of
1,124 patients exposed to IMBRUVICA ® in clinical trials. These events have occurred
particularly in patients with cardiac risk factors, hypertension, acute infections, and a
previous history of cardiac arrhythmias.
Periodically monitor patients clinically for cardiac arrhythmias. Obtain an ECG for
patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness, syncope,
chest pain) or new onset dyspnea. Manage cardiac arrhythmias appropriately, and if
it persists, consider the risks and benefits of IMBRUVICA ® treatment and follow dose
modification guidelines.
Hypertension: Hypertension of any grade occurred in 12% of 1,124 patients treated with
IMBRUVICA ® in clinical trials. Grade 3 or greater hypertension occurred in 5% of patients
with a median time to onset of 5.9 months (range, 0.03 to 24 months).
Monitor blood pressure in patients treated with IMBRUVICA ® and initiate or adjust
anti-hypertensive medication throughout treatment with IMBRUVICA ® as appropriate.
Second Primary Malignancies: Other malignancies (10%) including non-skin carcinomas
(4%) have occurred in 1,124 patients treated with IMBRUVICA ® in clinical trials. The most
frequent second primary malignancy was non-melanoma skin cancer (6%).