b'IMPORTANT SAFETY INFORMATION (continued)WARNINGS AND PRECAUTIONS (continued)InfectionsFatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients, most commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.CytopeniasZANUBRUTINIB (BRUKINSA ) Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy. Grade 4 IS INCLUDED AS Aneutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients.CATEGORY 1 PREFERREDMonitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.TREATMENT OPTION Second Primary MalignanciesSecond primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with for front-line and previously treatedBRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer, Waldenstrm macroglobulinemia (WM)reported in 7% of patients. Other second primary malignancies included malignant solid tumors (4.0%), in the NCCN Clinical Practice Guidelinesmelanoma (1.7%) and hematologic malignancies (1.2%). Advise patients to use sun protection and monitor in Oncology (NCCN Guidelines) 1 *patients for the development of second primary malignancies.Cardiac ArrhythmiasAtrialbrillation and atrialutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. BRUKINSA is a treatment option with demonstratedPatients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or ef cacy and safety bene ts for patients with WM higher events were reported in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrialbrillation and atrialutter and manage as appropriate.Embryo-Fetal ToxicityBased onndings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and To learn more about the Bruton tyrosine kinase (BTK) inhibitor BRUKINSAfor 1 week after the last dose.and all its indications, visit BRUKINSA.com If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.ADVERSE REACTIONS*As primary therapy or therapy for previously treated patients. The most common adverse reactions, including laboratory abnormalities, in30% of patients who receivedReferenced with permission from the National Comprehensive Cancer Network(NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines ).BRUKINSA (N = 847) included decreased neutrophil count (54%), upper respiratory tract infection (47%), Waldenstrm Macroglobulinemia/Lymphoplasmacytic Lymphoma. Version 1.2022. All rights reserved. Accessed October 1, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content,decreased platelet count (41%), hemorrhage (35%), decreased lymphocyte count (31%), rash (31%) and use or application and disclaims any responsibility for their application or use in any way.musculoskeletal pain (30%).DRUG INTERACTIONSINDICATION CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA BRUKINSA is indicated for the treatment of adult patients with Waldenstrms macroglobulinemia (WM). dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.IMPORTANT SAFETY INFORMATION CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.WARNINGS AND PRECAUTIONS SPECIFIC POPULATIONSHemorrhage Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treatedis 80 mg orally twice daily.with BRUKINSA monotherapy. Grade 3 or higher hemorrhage events including intracranial andPlease see Brief Summary of Prescribing Information on the following pages.gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade occurred in 35% of patients treated with BRUKINSA monotherapy.Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulationReference: 1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may furtherB-Cell Lymphomas Version 5.2021-September 22, 2021.increase the risk of hemorrhage. Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the bene t-risk of withholding BRUKINSA for 3-7 days pre- and post-surgeryBRUKINSA and BeiGene are registered trademarks depending upon the type of surgery and the risk of bleeding. owned by BeiGene, Ltd.BeiGene, Ltd. 2021 Please see Brief Summary of Prescribing Information on the following pages. All Rights Reserved. 1021-BRU-PRC-027 10/21BeiGene Market Access - Brukinsa WMTrim: 15.75 x 10.751021-BRU-PRC-027 05/22 Bleed: 0.125 all aroundU.S. Medicine four page (2 spreads) journal ad Safety:0.5 all around'