b'BRIEF SUMMARY OF PRESCRIBING INFORMATION Fatal events within 30 days of the last dose of BRUKINSA occurred in 8 (7%) of 118 patients with MCL. Fatal cases includedTable 5 summarizes the adverse reactions in Cohort 1 in ASPEN. * Includes 2 fatal events of COVID-19 pneumonia.aUpper respiratory tract infections includes upper respiratory tract infection, nasopharyngitis, sinusitis, tonsillitis, rhinitis, viral upper respiratory tract infection.FOR BRUKINSA (zanubrutinib) pneumonia in 2 patients and cerebral hemorrhage in one patient. Table 5: Adverse Reactions ( 10%) Occurring in Patients with WM Who Received BRUKINSA in Cohort 1bUrinary tract infection includes urinary tract infection, cystitis, Escherichia urinary tract infection, pyelonephritis, cystitis. SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION Serious adverse reactions were reported in 36 patients (31%). The most frequent serious adverse reactions that occurredBody System Adverse Reaction BRUKINSA (N=101) Ibrutinib (N=98) cPneumonia includes COVID-19 pneumonia, pneumonia, bronchopulmonary aspergillosis, lower respiratory tract infection, organizing pneumonia.d Diarrhea includes diarrhea and diarrhea hemorrhagic.were pneumonia (11%) and hemorrhage (5%). e Abdominal pain includes abdominal pain, abdominal pain upper, abdominal discomfort.1 INDICATIONS AND USAGE All GradesGrade 3 All GradesGrade 3f Bruising includes contusion, ecchymosis, increased tendency to bruise, post procedural contusion.Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions(%) or 4 (%) (%) or 4 (%) g Rash includes rash, rash maculo-papular, rash pruritic, dermatitis, dermatitis allergic, dermatitis atopic, dermatitis contact, drug reaction with1.1 Mantle Cell Lymphoma eosinophilia and systemic symptoms, erythema, photosensitivity reaction, rash erythematous, rash papular, seborrheic dermatitis.in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) Infections and infestation Upper respiratory44 0 40 2 Musculoskeletal pain includes back pain, arthralgia, musculoskeletal pain, myalgia, pain in extremity, musculoskeletal chest pain, bone pain, BRUKINSA is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least patient experienced an adverse reaction leading to dose reduction (hepatitis B). tract infection hone prior therapy. imusculoskeletal discomfort, neck pain. Table 3 summarizes the adverse reactions in BGB-3111-206 and BGB-3111-AU-003. Hemorrhage includes epistaxis, hematuria, hemorrhoidal hemorrhage, hematoma, hemoptysis, conjunctival hemorrhage, diarrhea hemorrhagic, hemorrhagePneumonia 12 4 26 10 urinary tract, mouth hemorrhage, pulmonary hematoma, subcutaneous hematoma, gingival bleeding, melena, upper gastrointestinal hemorrhage.This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.1)]. j Fatigue includes fatigue, lethargy, asthenia.Continued approval for this indication may be contingent upon verification and description of clinical benefit in aTable 3: Adverse Reactions ( 10%) in Patients Receiving BRUKINSA in BGB-3111-206 and BGB-3111-AU-003 Trials Urinary tract infection 11 0 13 2 k Cough includes cough and productive cough.confirmatory trial. Body System Adverse Reaction Percent of PatientsGastrointestinal disorders Diarrhea 22 3 34 2 Clinically relevant adverse reactions in 10% of patients who received BRUKINSA included peripheral neuropathy,1.2 Waldenstrms Macroglobulinemia (N=118) Nausea 18 0 13 1 second primary malignancies, dizziness, edema, headache, petechiae, purpura and atrial fibrillation or flutter. BRUKINSA is indicated for the treatment of adult patients with Waldenstrms macroglobulinemia (WM). All GradesGrade 3 orConstipation 16 0 7 0 Table 8 summarizes selected laboratory abnormalities.1.3 Marginal Zone Lymphoma % Higher % Table 8: Select Laboratory Abnormalities ( 20%) That Worsened from Baseline in Patients with MZLVomiting 12 0 14 1BRUKINSA is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) Blood and lymphatic system disorders Neutropenia and38 15 # Laboratory Abnormality1 BRUKINSAwho have received at least one anti-CD20-based regimen. Neutrophil count decreased General disorders Fatigue 31 1 25 1and administration site conditions All Grades (%) Grade 3 or 4 (%)This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.3)].Thrombocytopenia and 27 5 Pyrexia 16 4 13 2Continued approval for this indication may be contingent upon verification and description of clinical benefit in aPlatelet count decreased Edema peripheral 12 0 20 0 Hematologic abnormalitiesconfirmatory trial. Leukopenia and25 5 Skin and subcutaneous tissueBruising* 20 0 34 0 Neutrophils decreased 43 154 CONTRAINDICATIONS: None. White blood count decreased disorders Rashll 29 0 32 0 Platelets decreased 33 10Anemia and Hemoglobin decreased 14 8 Pruritus 11 1 6 0 Lymphocytes decreased 32 85 WARNINGS AND PRECAUTIONSMusculoskeletal and connective tissueMusculoskeletal pain 45 9 39 1 Hemoglobin decreased 26 65.1 Hemorrhage Infections and infestations Upper respiratory tract infection 39 0 disorders Chemistry abnormalitiesFatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSAPneumonia 15 10^ Muscle spasms 10 0 28 1 Glucose increased 54 4.6monotherapy. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria andNervous system disorders Headache 18 1 14 1hemothorax have been reported in 3.4% of patients treated with BRUKINSA monotherapy. Hemorrhage events of any grade,Urinary tract infection 11 0.8 Dizziness 13 1 12 0 Creatinine increased 34 1.1excluding purpura and petechiae, occurred in 35% of patients. Skin and subcutaneous tissue disorders RashII 36 0 Respiratory, thoracic andCough 16 0 18 0 Phosphate decreased 27 2.3Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Bruising* 14 0 mediastinal disorders Dyspnea 14 0 7 0 Calcium decreased 23 0Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.ALT increased 22 1.1Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs.Gastrointestinal disorders Diarrhea 23 0.8 Vascular disorders Hemorrhage 42 4 43 9 1 The denominator used to calculate the rate varied from 87 to 88 based on the number of patients with a baseline value and at least one post-treatment value. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgeryConstipation 13 0 Hypertension 14 9 19 14 7 DRUG INTERACTIONSand the risk of bleeding.* Bruising includes all related terms containing bruise, contusion, or ecchymosis.Vascular disorders Hypertension 12 3.4H emorrhage includes epistaxis, hematuria, conjunctival hemorrhage, hematoma, rectal hemorrhage, periorbital hemorrhage, mouth hemorrhage, 7.1 Effect of Other Drugs on BRUKINSA 5.2 Infections post procedural hemorrhage, hemoptysis, skin hemorrhage, hemorrhoidal hemorrhage, ear hemorrhage, eye hemorrhage, hemorrhagic diathesis, Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients withHemorrhage11 3.4^ periorbital hematoma, subdural hemorrhage, wound hemorrhage, gastric hemorrhage, lower gastrointestinal hemorrhage, spontaneousTable 9: Drug Interactions that Affect Zanubrutinibhematoma, traumatic hematoma, traumatic intracranial hemorrhage, tumor hemorrhage, retinal hemorrhage, hematochezia, diarrhea hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 27% of patients,Musculoskeletal and connective tissue disorders Musculoskeletal pain 14 3.4 hemorrhagic, hemorrhage, melena, post procedural hematoma, subdural hematoma, anal hemorrhage, hemorrhagic disorder, pericardialModerate and Strong CYP3A Inhibitorsmost commonly pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.hemorrhage, postmenopausal hemorrhage, stoma site hemorrhage, subarachnoid hemorrhage.# Fatigue includes asthenia, fatigue, lethargy. Clinical ImpactCo-administration with a moderate or strong CYP3A inhibitor increases zanubrutinib C maxandConsider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia, and other infections according to standardMusculoskeletal pain includes back pain, arthralgia, pain in extremity, musculoskeletal pain, myalgia, bone pain, spinal pain, musculoskeletalAUC [see Clinical Pharmacology (12.3)] which may increase the risk of BRUKINSA toxicities.of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs andMetabolism and nutrition disorders Hypokalemia 14 1.7 chest pain, neck pain, arthritis, musculoskeletal discomfort.Pneumonia includes lower respiratory tract infection, lung infiltration, pneumonia, pneumonia aspiration, pneumonia viral.Prevention or Reduce BRUKINSA dosage when co-administered with moderate or strong CYP3A inhibitors symptoms of infection and treat appropriately.llRash includes all related terms rash, maculo-papular rash, erythema, rash erythematous, drug eruption, dermatitis allergic, dermatitis atopic,management [see Dosage and Administration (2.3)].5.3 Cytopenias Respiratory, thoracic and mediastinal disorders Cough 12 0 rash pruritic, dermatitis, photodermatosis, dermatitis acneiform, stasis dermatitis, vasculitic rash, eyelid rash, urticaria, skin toxicity.Moderate and Strong CYP3A InducersUpper respiratory tract infection includes upper respiratory tract infection, laryngitis, nasopharyngitis, sinusitis, rhinitis, viral upper respiratory Grade 3 or 4 cytopenias, including neutropenia (26%), thrombocytopenia (11%) and anemia (8%) based on laboratorytract infection, pharyngitis, rhinovirus infection, upper respiratory tract congestion. Clinical ImpactCo-administration with a moderate or strong CYP3A inducer decreases zanubrutinib C maxmeasurements, developed in patients treated with BRUKINSA monotherapy [see Adverse Reactions (6.1)]. Grade 4^ Includes fatal adverse reaction. Clinically relevant adverse reactions in 10% of patients who received BRUKINSA included localized infection, atrialand AUC [see Clinical Pharmacology (12.3)] which may reduce BRUKINSA efficacy.neutropenia occurred in 13% of patients, and Grade 4 thrombocytopenia occurred in 3.6% of patients. * Bruising includes all related terms containing bruise, bruising, contusion, ecchymosis. fibrillation or atrial flutter and hematuria. Hemorrhage includes all related terms containing hemorrhage, hematoma. Prevention or Avoid co-administration of BRUKINSA with moderate or strong CYP3A inducers Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinueMusculoskeletal pain includes musculoskeletal pain, musculoskeletal discomfort, myalgia, back pain, arthralgia, arthritis. Table 6 summarizes the laboratory abnormalities in ASPEN. management [see Dosage and Administration (2.3)].treatment as warranted [see Dosage and Administration (2.4)]. Treat using growth factor or transfusions, as needed. Pneumonia includes pneumonia, pneumonia fungal, pneumonia cryptococcal, pneumonia streptococcal, atypical pneumonia, lung infection, Table 6: Select Laboratory Abnormalities* ( 20%) That Worsened from Baseline in Patients with WM Who Received lower respiratory tract infection, lower respiratory tract infection bacterial, lower respiratory tract infection viral. 8 USE IN SPECIFIC POPULATIONS 5.4 Second Primary MalignanciesI Rash includes all related terms containing rash.I BRUKINSA in Cohort 1Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSAUpper respiratory tract infection includes upper respiratory tract infection, upper respiratory tract infection viral.Laboratory Abnormality BRUKINSA1 Ibrutinib1 8.1 Pregnancy monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer reported in 8% of patients.Risk Summary Other second primary malignancies included malignant solid tumors (4.0%), melanoma (1.7%) and hematologicOther clinically significant adverse reactions that occurred in 10% of patients with mantle cell lymphoma includeAll Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Based on findings in animals, BRUKINSA can cause fetal harm when administered to pregnant women. There are no available major hemorrhage (defined asGrade 3 hemorrhage or CNS hemorrhage of any grade) (5%), hyperuricemia (6%) Hematologic Abnormalities data on BRUKINSA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse malignancies (1.2%). Advise patients to use sun protection and monitor patients for the development of second primaryand headache (4.2%). maternal or fetal outcomes. In animal reproduction studies, oral administration of zanubrutinib to pregnant rats during the malignancies. Neutrophils decreased 50 24 34 9 period of organogenesis was associated with fetal heart malformation at approximately 5-fold human exposures (see Data). 5.5 Cardiac Arrhythmias Table 4: Selected Laboratory Abnormalities* ( 20%) in Patients with MCL Platelets decreased 35 8 39 5 Women should be advised to avoid pregnancy while taking BRUKINSA. If BRUKINSA is used during pregnancy, or if the patient Atrial fibrillation and atrial flutter were reported in 3.2% of patients treated with BRUKINSA monotherapy. Patients within Studies BGB-3111-206 and BGB-3111-AU-003 becomes pregnant while taking BRUKINSA, the patient should be apprised of the potential hazard to the fetus.cardiac risk factors, hypertension and acute infections may be at increased risk. Grade 3 or higher events were reported Laboratory Parameter Percent of Patients (N=118) Hemoglobin decreased 20 7 20 7 The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies in 1.1% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter All Grades (%) Grade 3 or 4 (%) Chemistry Abnormalities have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.and manage as appropriate [see Dosage and Administration (2.4)]. Hematologic abnormalities Bilirubin increased 12 1.0 33 1.0 Data 5.6 Embryo-Fetal Toxicity Neutrophils decreased 45 20 Calcium decreased 27 2.0 26 0 Animal Data Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration Embryo-fetal development toxicity studies were conducted in both rats and rabbits. Zanubrutinib was administered orally of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations Platelets decreased 40 7 Creatinine increased 31 1.0 21 1.0 to pregnant rats during the period of organogenesis at doses of 30, 75, and 150 mg/kg/day. Malformations in the heart at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily.Hemoglobin decreased 27 6 Glucose increased 45 2.3 33 2.3 (2- or 3-chambered hearts) were noted at all dose levels in the absence of maternal toxicity. The dose of 30 mg/kg/day is Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid approximately 5 times the exposure (AUC) in patients receiving the recommended dose of 160 mg twice daily.fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patientLymphocytosis 41 16 Potassium increased 24 2.0 12 0 Administration of zanubrutinib to pregnant rabbits during the period of organogenesis at 30, 70, and 150 mg/kg/day resulted becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use inChemistry abnormalities Urate increased 16 3.2 34 6 in post-implantation loss at the highest dose. The dose of 150 mg/kg is approximately 32 times the exposure (AUC) in Specific Populations (8.1)]. Blood uric acid increased 29 2.6 patients at the recommended dose and was associated with maternal toxicity.Phosphate decreased 20 3.1 18 0 In a pre- and post-natal developmental toxicity study, zanubrutinib was administered orally to rats at doses of 30, 75, and 6 ADVERSE REACTIONS ALT increased 28 0.9 *Based on laboratory measurements.150 mg/kg/day from implantation through weaning. The offspring from the middle and high dose groups had decreased The following clinically significant adverse reactions are discussed in more detail in other sections of the labeling: Bilirubin increased 24 0.91 The denominator used to calculate the rate varied from 86 to 101 based on the number of patients with a baseline value and at least one post-treatment value. body weights preweaning, and all dose groups had adverse ocular findings (e.g., cataract, protruding eye). The dose of*Based on laboratory measurements. Marginal Zone Lymphoma30 mg/kg/day is approximately 5 times the AUC in patients receiving the recommended dose. Hemorrhage [see Warnings and Precautions (5.1)]A symptomatic lymphocytosis is a known effect of BTK inhibition.The safety of BRUKINSA was evaluated in 88 patients with previously treated MZL in two single-arm clinical studies, BGB-3111-2148.2 LactationInfections [see Warnings and Precautions (5.2)] and BGB-3111-AU-003 [see Clinical Studies (14.3)]. The trials required an absolute neutrophil count1 x 109/L, platelet count50Risk Summary Waldenstrms Macroglobulinemia (WM) or75 x 109/L and adequate hepatic function and excluded patients requiring a strong CYP3A inhibitor or inducer. Patients receivedThere are no data on the presence of zanubrutinib or its metabolites in human milk, the effects on the breastfed child, orCytopenias [see Warnings and Precautions (5.3)] The safety of BRUKINSA was investigated in two cohorts of Study BGB-3111-302 (ASPEN). Cohort 1 included 199 patientsBRUKINSA 160 mg twice daily (97%) or 320 mg once daily (3%). The median age in both studies combined was 70 years (range:the effects on milk production. Because of the potential for serious adverse reactions from BRUKINSA in a breastfed child,Second Primary Malignancies [see Warnings and Precautions (5.4)] with MYD88 mutation (MYD88MUT)WM, randomized to and treated with either BRUKINSA (101 patients) or ibrutinib 37 to 95), 52% were male, 64% were Caucasian and 19% were Asian. Most patients (92%) had an ECOG performance status of advise lactating women not to breastfeed during treatment with BRUKINSA and for two weeks following the last dose.MUT 0 to 1. Eighty percent received BRUKINSA for 6 months or longer, and 67% received treatment for more than one year. 8.3 Females and Males of Reproductive PotentialCardiac Arrhythmias [see Warnings and Precautions (5.5)] (98 patients). The trial also included a non-randomized arm, Cohort 2, with 26 wild type MYD88 (MYD88 )WM patients Two fatal adverse reactions (2.3%) occurred within 30 days of the last dose of BRUKINSA, including myocardial infarctionPregnancy Testing 6.1 Clinical Trials Experience and 2 patients with unknown MYD88 status [see Clinical Studies (14.2)]. and a Covid-19 related death. Pregnancy testing is recommended for females of reproductive potential prior to initiating BRUKINSA therapy.Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials Among patients who received BRUKINSA, 93% were exposed for 6 months or longer, and 89% were exposed for greaterSerious adverse reactions occurred in 40% of patients. The most frequent serious adverse reactions were pyrexia (8%) and pneumonia (7%).Contraception of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed than 1 year. Adverse reactions lead to treatment discontinuation in 6% of patients, dose reduction in 2.3%, and dose interruption in 34%.Females in practice. In Cohort 1 of the ASPEN study safety population (N=101), the median age of patients who received BRUKINSA was The leading cause of dose modification was respiratory tract infections (13%) BRUKINSA can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. 70 years (45-87 years old); 67% were male, 86% were White, 4% were Asian and 10% were not reported (unknown race).Table 7 summarizes selected adverse reactions in BGB-3111-214 and BGB-3111-AU-003. Advise female patients of reproductive potential to use effective contraception during treatment with BRUKINSA and forThe data in the WARNINGS AND PRECAUTIONS reflect exposure to BRUKINSA in seven clinical trials, administered as a1 week following the last dose of BRUKINSA. If this drug is used during pregnancy, or if the patient becomes pregnantsingle agent at 160 mg twice daily in 730 patients, at 320 mg once daily in 105 patients, and at 40 mg to 160 mg once dailyIn Cohort 2 of the ASPEN study safety population (N=28), the median age of patients who received BRUKINSA was 72 Table 7: Adverse Reactions Occurring in10% Patients with MZL Who Received BRUKINSAwhile taking this drug, the patient should be informed of the potential hazard to a fetus.(0.125 to 0.5 times the recommended dosage) in 12 patients. Among 847 patients receiving BRUKINSA, 73% were exposed(39-87 years old); 50% were male, 96% were White and 4% were not reported (unknown race). Body System Adverse Reaction BRUKINSA (N=88) Males for at least 1 year, 57% were exposed for at least 2 years and 26% were exposed for at least 3 years.In Cohort 1, serious adverse reactions occurred in 44% of patients who received BRUKINSA.Serious adverse reactions All GradesGrade 3 orAdvise men to avoid fathering a child while receiving BRUKINSA and for 1 week following the last dose of BRUKINSA.In this pooled safety population, the most common adverse reactions, including laboratory abnormalities, in30% ofin 2% of patients included influenza (3%), pneumonia (4%), neutropenia and neutrophil count decreased (3%),% Higher % 8.4 Pediatric Use patients included neutrophil count decreased (54%), upper respiratory tract infection (47%), platelet count decreased hemorrhage (4%), pyrexia (3%) and febrile neutropenia (3%). In Cohort 2, serious adverse reactions occurred in 39% a Safety and effectiveness in pediatric patients have not been established.(41%), hemorrhage (35%), lymphocyte count decreased (31%), rash (31%) and musculoskeletal pain (30%). of patients. Serious adverse reactions in 2 patients included pneumonia (14%). Infections and infestations Upper respiratory tract infections 26 3.4 8.5 Geriatric Use Mantle Cell Lymphoma (MCL) Permanent discontinuation of BRUKINSA due to an adverse reaction occurred in 2% of patients in Cohort 1 and includedUrinary tract infectionb 11 2.3 Of the 847 patients in clinical studies with BRUKINSA, 53% were65 years of age, and 20% were75 years of age.hemorrhage (1 patient), neutropenia and neutrophil count decreased (1 patient); in Cohort 2, permanent discontinuation Pneumoniac 10 6 No overall differences in safety or effectiveness were observed between younger and older patients.The safety of BRUKINSA was evaluated in 118 patients with MCL who received at least one prior therapy in two of BRUKINSA due to an adverse reaction occurred in 7% of patients and included subdural hemorrhage (1 patient) andd 8.6 Renal Impairment single-arm clinical trials, BGB-3111-206 [NCT03206970] and BGB-3111-AU-003 [NCT02343120] [see Clinical Studiesdiarrhea (1 patient).Gastrointestinal disorders Diarrhea 25 3.4No dosage modification is recommended in patients with mild, moderate, or severe renal impairment (CLcr15 mL/min, (14.1)]. The median age of patients who received BRUKINSA in studies BGB-3111-206 and BGB-3111-AU-003 was Dosage interruptions of BRUKINSA due to an adverse reaction occurred in 32% of patients in Cohort 1 and in 29% in Abdominal paine 14 2.3 estimated by Cockcroft-Gault). Monitor for BRUKINSA adverse reactions in patients on dialysis [see Clinical Pharmacology (12.3)].62 years (range: 34 to 86), 75% were male, 75% were Asian, 21% were White, and 94% had an ECOG performance statusCohort 2. Adverse reactions which required dosage interruption in 2% of patients included neutropenia, vomiting,Nausea 13 0 8.7 Hepatic Impairment of 0 to 1. Patients had a median of 2 prior lines of therapy (range: 1 to 4). The BGB-3111-206 trial required a platelet count9 9 hemorrhage, thrombocytopenia and pneumonia in Cohort 1. Adverse reactions leading to dosage interruption in Skin and subcutaneous tissue disorders Bruisingf 24 0 Dosage modification of BRUKINSA is recommended in patients with severe hepatic impairment [see Dosage and75 x 10/L and an absolute neutrophil count1 x 10/L independent of growth factor support, hepatic enzymes2.5 xAdministration (2.2)]. The safety of BRUKINSA has not been evaluated in patients with severe hepatic impairment.upper limit of normal, total bilirubin1.5 x ULN. The BGB-3111-AU-003 trial required a platelet count50 x 109/L and an 2 patients in Cohort 2 included pneumonia and pyrexia. Rashg 21 0 No dosage modification is recommended in patients with mild to moderate hepatic impairment. Monitor for BRUKINSA absolute neutrophil count1 x 109/L independent of growth factor support, hepatic enzymes3 x upper limit of normal,Dose reductions of BRUKINSA due to an adverse reaction occurred in 11% of patients in Cohort 1 and in 7% in Cohort 2.Musculoskeletal and connective tissue disorders Musculoskeletal painh 27 1.1 adverse reactions in patients with hepatic impairment [see Clinical Pharmacology (12.3)].total bilirubin1.5 x ULN. Both trials required a CLcr30 mL/min. Both trials excluded patients with prior allogeneicAdverse reactions which required dose reductions in 2% of patients included neutropenia in Cohort 1. Adverse reactioni Distributed and Marketed by: hematopoietic stem cell transplant, exposure to a BTK inhibitor, known infection with HIV and serologic evidence of activeleading to dose reduction occurred in 2 patients in Cohort 2 (each with one event: diarrhea and pneumonia). Vascular disorders Hemorrhage23 1.1 BeiGene USA, Inc. hepatitis B or hepatitis C infection and patients requiring strong CYP3A inhibitors or strong CYP3A inducers. PatientsGeneral disorders Fatiguej 21 2.3 2955 Campus Drive, Suite 200received BRUKINSA 160 mg twice daily or 320 mg once daily. Among patients receiving BRUKINSA, 79% were exposed Respiratory, thoracic and mediastinal disorders Coughk 10 0 San Mateo, CA 94403 for 6 months or longer, and 68% were exposed for greater than one year. BRUKINSA is a registered trademark owned by BeiGene, Ltd.BeiGene, Ltd. 2021 All Rights Reserved. 0721-BRU-PRC-028-r1 09/2021BeiGene 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'