b'B:8.125"T:7.875"S:7.375"IMPORTANT SAFETY INFORMATIONMonitor and evaluate patients for fever and infections and WARNINGS AND PRECAUTIONS treat appropriately. Cytopenias: In 645 patients with B-cell malignancies who Hemorrhage: Fatal bleeding events have occurred in patientsreceived IMBRUVICA as a single agent, Grade 3 or 4 S:10.25" T:10.75" B:11"who received IMBRUVICA. Major hemorrhage ( Grade 3,neutropenia occurred in 23% of patients, Grade 3 or 4 serious, or any central nervous system events; e.g., intracranialthrombocytopenia in 8% and Grade 3 or 4 anemia in 3%,hemorrhage [including subdural hematoma], gastrointestinalbased on laboratory measurements.bleeding, hematuria, and post procedural hemorrhage) occurred inMonitor complete blood counts monthly. 4% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA in 27 clinical trials. Bleeding events,Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias including bruising and petechiae, occurred in 39% of patients whohave occurred with IMBRUVICA. Grade 3 or greater ventricular received IMBRUVICA. tachyarrhythmias occurred in 0.2% of patients and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4% of 1,476 The mechanism for the bleeding events is not well understood. patients who received IMBRUVICA in clinical trials. These events Use of either anticoagulant or antiplatelet agents concomitantlyhave occurred particularly in patients with cardiac risk factors, with IMBRUVICA increases the risk of major hemorrhage. Acrosshypertension, acute infections, and a previous history ofclinical trials, 3.1% of 2,838 patients who received IMBRUVICAcardiac arrhythmias.without antiplatelet or anticoagulant therapy experienced majorPeriodically monitor patients clinically for cardiac arrhythmias. hemorrhage. The addition of antiplatelet therapy with or withoutObtain an ECG for patients who develop arrhythmic symptoms anticoagulant therapy increased this percentage to 4.4%, and(e.g., palpitations, lightheadedness, syncope, chest pain) or new the addition of anticoagulant therapy with or without antiplateletonset dyspnea. Manage cardiac arrhythmias appropriately, and if it therapy increased this percentage to 6.1%. Consider the risks persists, consider the risks and benefits of IMBRUVICA treatment and benefits of anticoagulant or antiplatelet therapy whenco-administered with IMBRUVICA. Monitor for signs andand follow dose modification guidelines.symptoms of bleeding.Hypertension: Hypertension occurred in 19% of 1,476 patients Consider the benefit-risk of withholding IMBRUVICA for at leastwho received IMBRUVICA in clinical trials. Grade 3 or greater 3 to 7 days pre- and post-surgery depending upon the type ofhypertension occurred in 8% of patients. Based on data from 1,124 surgery and the risk of bleeding. of these patients, the median time to onset was 5.9 months (range, Infections: Fatal and non-fatal infections (including bacterial, viral,0.03 to 24 months).or fungal) have occurred with IMBRUVICA therapy. Grade 3 orMonitor blood pressure in patients treated with IMBRUVICAand initiate or adjust anti-hypertensive medication throughout treatment greater infections occurred in 21% of 1,476 patients who receivedIMBRUVICA in clinical trials. Cases of progressive multifocalwith IMBRUVICAas appropriate.leukoencephalopathy (PML) and Pneumocystis jirovecii pneumoniaSecond Primary Malignancies: Other malignancies (10%), (PJP) have occurred in patients treated with IMBRUVICA. Considerincluding non-skin carcinomas (4%), occurred among the prophylaxis according to standard of care in patients who are at1,476 patients who received IMBRUVICA in clinical trials. The increased risk for opportunistic infections. most frequent second primary malignancy wasnon-melanoma skin cancer (6%).Date: October 21, 2020 11:39 AM Brand: IMBRUVICAColors: CMYKFile Name: PRC-07105a_853809_v1 Size: 7.875" x 10.75"page1 Left Hand Page 100, 0, 0, 35 =Customer Code: PRC-07105a Description: Living Longer Without Progression 54, 0, 100, 0 =We Are Alexander #: 853809 Pub: US Medicine 2021 Directory 99, 14, 3, 0 ='