b'Table 15 summarizes adverse reactions in BGB-3111-212. 7 DRUG INTERACTIONS VA Heart of TexasVA Rocky Mountain Table 15: Adverse Reactions in 10% of Patients with Relapsed or Refractory FL Who Received BRUKINSA7.1 Effect of Other Drugs on BRUKINSA 17 Healthcare19 Networkin Study BGB-3111-212 Table 17: Drug Interactions that Affect ZanubrutinibBGB-3111-212 Moderate and Strong CYP3A Inhibitors NetworkBRUKINSA + Obinutuzumab Obinutuzumab Clinical Coadministration with a moderate or strong CYP3A inhibitor increases zanubrutinib C maxand System Organ Class (N=143) (N=71) Impact AUC [see Clinical Pharmacology (12.3)] which may increase the risk of BRUKINSA toxicities.Preferred Term All Grades Grade 3 or 4 All Grades Grade 3 or 4 Prevention orReduce BRUKINSA dosage when coadministered with moderate or strong CYP3A (%) (%) (%) (%) management inhibitors [see Dosage and Administration (2.3)].General disorders and administration site conditionsFatiguea,b 27 1.4 25 1.4 Moderate and Strong CYP3A InducersPyrexia 13 0 20 0 ClinicalCoadministration with a moderate or strong CYP3A inducer decreases zanubrutinib C maxMusculoskeletal and connective tissue disorders Impact and AUC [see Clinical Pharmacology (12.3)] which may reduce BRUKINSA efficacy.Musculoskeletal paina,c 22 3.5 23 1.4Avoid coadministration of BRUKINSA with strong CYP3A inducers Vascular disorders Prevention or[see Dosage and Administration (2.3)].a,d managementAvoid coadministration of BRUKINSA with moderate CYP3A inducers [see Dosage and Hemorrhage 20 1.4 10 1.4Administration (2.3)]. If these inducers cannot be avoided, increase BRUKINSA dosage to Gastrointestinal disorders 320 mg twice daily [see Dosage and Administration (2.3)].Diarrhea 18 2.8 17 1.4Constipation 13 0 9 0 8 USE IN SPECIFIC POPULATIONS Abdominal paina 11 2.1 11 0 8.1 PregnancyInfections and infestations Risk Summary a,e There are no available data on BRUKINSA use in pregnant women to evaluate for a drug-associated risk of Upper respiratory tract17 2.8 10 0 Based on findings in animals, BRUKINSA can cause fetal harm when administered to pregnant women.VISN 10VA Heart of Texas Health CareVISN 12VA Rocky Mountain Networkinfection a,f, major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, oralNetworkPneumonia * 15 13 11 7 administration of zanubrutinib to pregnant rats during the period of organogenesis was associated with fetal4100 E. Mississippi Ave., Suite 1100COVID-19a,* 13 9 11 4.2 heart malformation at approximately 5-fold human exposures (see Data). Women should be advised to avoid pregnancy while taking BRUKINSA. If BRUKINSA is used during pregnancy, or if the patient becomes pregnant2301 East Lamar Boulevard, Suite 650 Glendale, CO 80246Herpes virus infectiong 11 2.1 1.4 0 while taking BRUKINSA, the patient should be apprised of the potential hazard to the fetus.h Arlington, TX 76006 303-202-8165Urinary tract infection 10 1.4 7 0 The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Respiratory, thoracic, and mediastinal disorders All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general817-652-1111a population, the estimated background risk of major birth defects and miscarriage in clinically recognizedwww.visn19.va.govCough a, 14 0 14 0 pregnancies is 2% to 4% and 15% to 20%, respectively. www.heartoftexas.va.govDyspnea * 11 2.1 13 0 DataNetwork Director Mrs. Sunaina Kumar-GiebelSkin and subcutaneous tissue disorders Animal Data a,i Network Director Wendell Jones, MD, MBA Acting Deputy Network Director Eliott VanderStekRash 11 0 14 0 Embryo-fetal development toxicity studies were conducted in both rats and rabbits. Zanubrutinib wasadministered orally to pregnant rats during the period of organogenesis at doses of 30, 75, and 150 mg/kg/day.Deputy Network Director Jamie Park, EdD Deputy Chief Medical Officer Ann Jodway* Includes fatal outcomes: COVID-19 (3 patients), pneumonia (2 patients), dyspnea (1 patient).Malformations in the heart (2 or 3-chambered hearts) were noted at all dose levels in the absence of maternal aIncludes multiple related terms. toxicity. The dose of 30 mg/kg/day is approximately 5 times the exposure (AUC) in patients receiving theChief Medical Officer Stephen R. Holt, MD Pharmacist Executive Tanya HoodbFatigue: Fatigue, asthenia, and lethargy.cMusculoskeletal pain: Back pain, musculoskeletal pain, musculoskeletal discomfort, noncardiac chest pain, neck pain, pain inrecommended dose of 160 mg twice daily. Deputy Chief Medical Officer Rajani Potu, MD Chief Financial Officer Elliot VanderStekextremity, myalgia, spinal pain, bone pain, arthralgia, and related terms. Administration of zanubrutinib to pregnant rabbits during the period of organogenesis at 30, 70, and 150 mg/kg/day dHemorrhage: All terms containing hematoma, hemorrhage, hemorrhagic, and related terms indicative of bleeding. resulted in postimplantation loss at the highest dose. The dose of 150 mg/kg is approximately 32 times thePharmacist Executive Andrew Himsel Quality Management Officer Ruth HammondeUpper respiratory tract infection: Upper respiratory tract infection, sinusitis, pharyngitis, laryngitis, rhinitis, nasopharyngitis,exposure (AUC) in patients at the recommended dose and was associated with maternal toxicity.laryngopharyngitis, tonsillitis bacterial, and related terms. Quality Management Officer Denise Elliott, FACHE, LSSMBB Deputy Chief Nursing Officer Jeanne Aiken, MSN, RNf Pneumonia: Pneumonia, COVID-19 pneumonia, lung infiltration, lung consolidation, and related terms including specific types of infection. In a pre and postnatal developmental toxicity study, zanubrutinib was administered orally to rats at doses gHerpes virus infection: Herpes viral infection, herpes zoster, herpes simplex, herpes simplex reactivation, varicella, and Epstein-Barr viremia. of 30, 75, and 150 mg/kg/day from implantation through weaning. The offspring from the middle and highChief Financial Officer Mike Kuchyak Chief Nursing Officer Angela T. BrothershUrinary tract infection: Urinary tract infection, cystitis, pyelonephritis, and related terms.i Rash: Rash, erythema, dermatitis, drug eruption, skin reaction, and related terms. dose groups had decreased body weights preweaning, and all dose groups had adverse ocular findings (e.g., Health Promotion & Disease Prevention Lead Karla GallardoHealth Promotion & Disease Prevention Leadcataract, protruding eye).The dose of 30 mg/kg/day is approximately 5 times the AUC in patients receiving the Clinically relevant adverse reactions in 10% of patients who received BRUKINSA in combination withrecommended dose. Cauldwell RN MHI Rachel Thompsonobinutuzumab included bruising, edema, pruritus, petechiae, vomiting, headache, arthralgia, hypertension, sepsis, 8.2 Lactationcardiac arrhythmias, renal insufficiency, febrile neutropenia, transaminase elevation, and pneumonitis. Risk SummaryHealthcare Systems Pharmacy Benefits Manager Jonathan HoffmanThere are no data on the presence of zanubrutinib or its metabolites in human milk, the effects on the Table 16: Select Laboratory Abnormalities (20%) that Worsened from Baseline in Patients Who Receivedbreastfed child, or the effects on milk production. Because of the potential for serious adverse reactions from VA El Paso Healthcare System (El Paso, TX) Healthcare SystemsBRUKINSA in Study BGB-3111-212BRUKINSA in a breastfed child, advise lactating women not to breastfeed during treatment with BRUKINSA and BGB-3111-212 for two weeks following the last dose.VA North Texas Healthcare SystemVA Eastern Oklahoma Healthcare System (Muskogee, OK)a BRUKINSA + Obinutuzumab Obinutuzumab 8.3 Females and Males of Reproductive PotentialWest Texas VA Health Care System (Big Spring, TX)VA Oklahoma City Healthcare System (Oklahoma City, OK)Laboratory Abnormality BRUKINSA can cause embryo-fetal harm when administered to pregnant women [see Use in Specific All Grades Grade 3 or 4 All Grades Grade 3 or 4 Populations (8.1)]. Medical CentersVA Eastern Colorado Healthcare System (Aurora, CO)(%) (%) (%) (%) Pregnancy Testing Hematologic abnormalities Pregnancy testing is recommended for females of reproductive potential prior to initiating BRUKINSA therapy.Thomas E. Creek VA Medical Center (Amarillo, TX) Medical CentersPlatelets decreased 65 11 43 11 Contraception Dallas VA Medical Center (Dallas, TX)Cheyenne VA Medical Center (Cheyenne, WY)Neutrophils decreased 47 17 42 14 FemalesAdvise female patients of reproductive potential to use effective contraception during treatment with BRUKINSA El Paso VA Clinic (El Paso, TX)Fort Harrison VA Medical Center (Fort Harrison, MT)Hemoglobin decreased 31 0.8 23 0 and for 1 week following the last dose of BRUKINSA. If this drug is used during pregnancy, or if the patient Lymphocytes decreased 30 11 51 25 becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus.El Paso Central VA Clinic (El Paso, TX)Grand Junction VA Medical Center (Grand Junction, CO)Chemistry Males Garland VA Medical Center (Garland, TX)Sheridan VA Medical Center (Sheridan, WY)Glucose increasedb 53 8 41 9 Advise men to avoid fathering a child while receiving BRUKINSA and for 1 week following the last dose of BRUKINSA.Harlingen VA Clinic (Harlingen, TX)George W. Wahlen VA Medical Center (Salt Lake City, UT)8.4 Pediatric UseAlanine aminotransferase23 0 28 0 Safety and effectiveness of BRUKINSA in pediatric patients have not been established.Audie L. Murphy Memorial Veterans Hospital increased 8.5 Geriatric Use (San Antonio, TX)Phosphate decreased 21 0.8 14 0aThe denominator used to calculate the rate was 122 in the BRUKINSA + obinutuzumab arm, and varied from 56 to 58 in theOf the 1729 patients with MCL, MZL,WM, CLL/SLL, and FL in clinical studies with BRUKINSA, 59% were 65 Sam Rayburn Memorial Veterans Center (Bonham, TX)years of age, and 21% were 75 years of age. Patients 65 years of age had numerically higher rates ofVISNbobinutuzumab arm, based on the number of patients with a baseline value and at least one post-treatment value. Grading is basedGrade 3 or higher adverse reactions and serious adverse reactions (57% and 38%, respectively) than patients Olin E. Teague VA Medical Center (Temple, TX) Wendell17on NCI CTCAE criteria.Nonfasting conditions. 65 years of age (51% and 29%, respectively). No overall differences in effectiveness were observed betweenJonesyounger and older patients.George H. OBrien Jr. VAMedical Center (Big Spring, TX)8.6 Renal ImpairmentNo dosage modification is recommended in patients with mild, moderate, or severe renal impairment(CLcr 15 mL/min, estimated by Cockcroft-Gault). Monitor for BRUKINSA adverse reactions in patientson dialysis [see Clinical Pharmacology (12.3)]. SunainaVISNManufactured for:8.7 Hepatic Impairment Kumar- 19BeiGene USA, Inc.1840 Gateway Dr., FL 3Dosage modification of BRUKINSA is recommended in patients with severe hepatic impairment [see DosageGiebelSan Mateo, CA 94404 and Administration (2.2)]. The safety of BRUKINSA has not been evaluated in patients with severe hepatic BRUKINSA is a registered trademark owned by BeiGene, Ltd. or its affiliates.impairment. No dosage modification is recommended in patients with mild to moderate hepatic impairment.BeiGene, Ltd. 2024 0721-BRU-PRC-027-r2 3/2024 Monitor for BRUKINSA adverse reactions in patients with hepatic impairment [see Clinical Pharmacology (12.3)].VISNTHEDIRECTORY'