b'IMPORTANT SAFETY INFORMATION(CONT)WARNINGS AND PRECAUTIONS(CONT)InfectionsFatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred inpatients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred. Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii 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.CytopeniasGrade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients. Monitor 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.Second Primary MalignanciesSecond primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.Cardiac ArrhythmiasSerious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter werereported in 4.4% of patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients withcardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients. Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.Hepatotoxicity, Including Drug-Induced Liver InjuryHepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA.Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.*In combination with obinutuzumab. Embryo-Fetal ToxicityBased on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration INDICATIONS 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. BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with: Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoidfathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patientChronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Waldenstrms macroglobulinemia (WM)Mantle cell lymphoma (MCL) who have received at least one prior therapy. ADVERSE REACTIONSRelapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen. The most common adverse reactions (30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%),Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines ofhemorrhage (32%), and musculoskeletal pain (31%).systemic therapy.The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability ofDRUG INTERACTIONSresponse. Continued approval for these indications may be contingent upon verification and description of clinical benefit inCYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg confirmatory trials. once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended IMPORTANT SAFETY INFORMATION with moderate CYP3A inducers.WARNINGS AND PRECAUTIONS SPECIFIC POPULATIONSHemorrhage Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3twice daily.or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported inPlease see Brief Summary of full Prescribing Information on following pages.3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients. Abbreviations: BTK, Bruton tyrosine kinase; R/R, relapsed/refractory.Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration ofReferences: 1. BRUKINSA. Package insert. BeiGene USA, Inc.; 2024. 2.Calquence. Package insert. AstraZeneca PharmaceuticalsBRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.LP; 2022. 3. Imbruvica. Package insert. Pharmacyclics LLC, Janssen Biotech, Inc; 2023.Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding. BRUKINSA and BeiGene are registered trademarks owned by BeiGene, Ltd or its affiliates. BeiGene, Ltd. 2024 All Rights Reserved. 0624-BRU-PRC-074 6/2024BeiGene Market AccessUS Med Print Ad A-size BeiGene Market AccessUS Med Print Ad A-size7.875" x 10.75" / 0.125" bleed / 0.375" safety margin 7.875" x 10.75" / 0.125" bleed / 0.375" safety marginPage 1 of 7 (left side of spread) Page 1 of 7 (right side of spread)'