b'B:8.125"T:7.875"S:6.875"IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Monitor and evaluate patients for fever and infections and treat Hemorrhage: Fatal bleeding events have occurred in patients whoappropriately.received IMBRUVICA. Major hemorrhage ( Grade 3, serious, or anyCytopenias: In 645 patients with B-cell malignancies who receivedS:9.75" T:10.75" B:11"central nervous system events; e.g., intracranial hemorrhage [includingIMBRUVICA as a single agent, grade 3 or 4 neutropenia occurred subdural hematoma], gastrointestinal bleeding, hematuria, and postin 23% of patients, grade 3 or 4 thrombocytopenia in 8% and procedural hemorrhage) occurred in 4% of patients, with fatalitiesgrade 3 or 4 anemia in 3%, based on laboratory measurements.occurring in 0.4% of 2,838 patients who received IMBRUVICA inMonitor complete blood counts monthly.27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39%, and excluding bruising and petechiaeCardiac Arrhythmias and Cardiac Failure: Fatal and serious occurred in 23% of patients who received IMBRUVICA, respectively. cardiac arrhythmias and cardiac failure have occurred with The mechanism for the bleeding events is not well understood. IMBRUVICA. Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of patients, Grade 3 or greater atrial fibrillation Use of either anticoagulant or antiplatelet agents concomitantlyand atrial flutter occurred in 4%, and Grade 3 or greater cardiac with IMBRUVICA increases the risk of major hemorrhage. Acrossfailure occurred in 1% of 1,476 patients who received IMBRUVICA clinical trials, 3.1% of 2,838 patients who received IMBRUVICAin clinical trials. These events have occurred particularly in patients without antiplatelet or anticoagulant therapy experienced majorwith cardiac risk factors, hypertension, acute infections, and a hemorrhage. The addition of antiplatelet therapy with or withoutprevious history of cardiac arrhythmias.anticoagulant therapy increased this percentage to 4.4%, and theAt baseline and then periodically, monitor patients clinically addition of anticoagulant therapy with or without antiplatelet therapyfor cardiac arrhythmias and cardiac failure. Obtain an ECG for increased this percentage to 6.1%. Consider the risks and benefitspatients who develop arrhythmic symptoms (e.g., palpitations, of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA. Monitor for signs and symptoms of bleeding. lightheadedness, syncope, chest pain) or new onset dyspnea. Manage cardiac arrhythmias and cardiac failure appropriately, Consider the benefit-risk of withholding IMBRUVICA for at leastand if it persists, consider the risks and benefits of IMBRUVICA 3 to 7 days pre- and post-surgery depending upon the type oftreatment and follow dose modification guidelines.surgery and the risk of bleeding. Hypertension: Hypertension occurred in 19% of 1,476 patients who Infections: Fatal and non-fatal infections (including bacterial, viral,received IMBRUVICA in clinical trials. Grade 3 or greater hypertension or fungal) have occurred with IMBRUVICA therapy. Grade 3 oroccurred in 8% of patients. Based on data from 1,124 of these patients, greater infections occurred in 21% of 1,476 patients who receivedthe median time to onset was 5.9 months (range, 0.03 to 24 months).IMBRUVICA in clinical trials. Cases of progressive multifocalMonitor blood pressure in patients treated with IMBRUVICA and leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Considerinitiate or adjust anti-hypertensive medication throughout treatment prophylaxis according to standard of care in patients who are atwith IMBRUVICA as appropriate. increased risk for opportunistic infections.Date: November 17, 2021 1:03 PM Brand: IMBRUVICAColors: CMYKFile Name: PRC-07705a_868128_v1 Size: 7.875" x 10.75"page 1(Left Hand Start) 100, 0, 0, 35 =Customer Code: PRC-07705a Description: Living Longer Without Progression 54, 0, 100, 0 =We Are Alexander #: 868128 Pub: U.S. Medicine Directory'