BRUKINSA zanubrutinib 80 mg Capsule, 120-count

1 INDICATIONS AND USAGE BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with: Mantle cell lymphoma (MCL) who have received at least one prior therapy. ( 1.1 ) This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Waldenström's macroglobulinemia (WM). ( 1.2 ) Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti–CD20-based regimen. ( 1.3 ) This indication is approved under accelerated approval based on overall response rate.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ( 1.4 ) Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.

( 1.5 ) This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

1.1Mantle Cell Lymphoma BRUKINSA is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.1) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

1.2Waldenström's Macroglobulinemia BRUKINSA is indicated for the treatment of adult patients with Waldenström's macroglobulinemia (WM) [see Clinical Studies (14.2) ] .

1.3Marginal Zone Lymphoma BRUKINSA is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti–CD20-based regimen. This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.3) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

1.4Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma BRUKINSA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) [see Clinical Studies (14.4) ] .

1.5Follicular Lymphoma BRUKINSA is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response [see Clinical Studies (14.5) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

2 DOSAGE AND ADMINISTRATION Recommended dosage: 160 mg orally twice daily or 320 mg orally once daily with or without food; swallow whole with water. Tablets can be split in half as prescribed by the healthcare provider. ( 2.1 ) Reduce BRUKINSA dose in patients with severe hepatic impairment.

( 2.2 , 8.7 ) Advise patients not to open, break, or chew capsules. ( 2.1 ) Advise patients not to chew or crush tablets. ( 2.1 ) Manage toxicity using treatment interruption, dose reduction, or discontinuation.

( 2.4 )

2.1Recommended Dosage The recommended dosage of BRUKINSA for monotherapy or in combination with obinutuzumab is 160 mg taken orally twice daily or 320 mg taken orally once daily until disease progression or unacceptable toxicity. Capsule Administration Instructions Administer BRUKINSA capsules with or without food [see Clinical Pharmacology (12.3) ] . Advise patients to swallow capsules whole with water and not to open, break, or chew capsules.

Tablet Administration Instructions Administer BRUKINSA tablets with or without food [see Clinical Pharmacology (12.3) ]. Advise patients to swallow tablets whole with water and not to chew or crush the tablets. The tablets can be split in half as prescribed by the healthcare provider.

Missed Dose If a dose of BRUKINSA is missed, it should be taken as soon as possible on the same day with a return to the normal schedule the following day.

2.2Dosage Modification for Use in Hepatic Impairment The recommended dosage of BRUKINSA for patients with severe hepatic impairment (Child-Pugh class C) is 80 mg orally twice daily; no dosage modification is recommended for patients with mild or moderate hepatic impairment (Child-Pugh class A or B) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ].

2.3Dosage Modifications for Drug Interactions Recommended dosage modifications of BRUKINSA for drug interactions are provided in Table 1 [see Drug Interactions (7.1) ] . Table 1: Dosage Modifications for Use with CYP3A Inhibitors or Inducers Coadministered Drug Recommended BRUKINSA Dosage (Starting Dose: 160 mg twice daily or 320 mg once daily) Clarithromycin 250 mg twice daily Since clarithromycin 250 mg twice daily acts as a moderate CYP3A inhibitor, it is recommended that patients be administered clarithromycin 250 mg twice daily with 80 mg BRUKINSA twice daily [see Clinical Pharmacology (12.3) ] .

80 mg twice daily Modify or interrupt zanubrutinib dose as recommended for adverse reactions [see Dosage and Administration (2.4) ] . Clarithromycin 500 mg twice daily 80 mg once daily Posaconazole suspension 100 mg once daily 80 mg twice daily Posaconazole suspension dosage higher than 100 mg once daily Posaconazole delayed-release tablets 300 mg once daily Posaconazole intravenous 300 mg once daily 80 mg once daily Other strong CYP3A inhibitor 80 mg once daily Moderate CYP3A inhibitor 80 mg twice daily Strong CYP3A inducer Avoid concomitant use.

Moderate CYP3A inducer Avoid concomitant use. If these inducers cannot be avoided, increase BRUKINSA dose to 320 mg twice daily. After discontinuation of a CYP3A inhibitor or moderate CYP3A inducer, resume previous dose of BRUKINSA [see Dosage and Administration (2.1 , 2.2) and Drug Interactions (7.1) ] .

2.4Dosage Modifications for Adverse Reactions Recommended dosage modifications of BRUKINSA for Grade 3 or higher adverse reactions are provided in Table 2. Table 2: Recommended Dosage Modifications for Adverse Reaction Adverse Reaction Adverse Reaction Occurrence Dosage Modification (Starting Dose: 160 mg twice daily or 320 mg once daily) Hematological toxicities [see Warnings and Precautions (5.3) ] Grade 3 or Grade 4 febrile neutropenia Platelet count decreased to 25,000-50,000/mm 3 with significant bleeding Neutrophil count decreased to <500/mm 3 (lasting more than 10 consecutive days) Platelet count decreased to <25,000/mm 3 (lasting more than 10 consecutive days) First Interrupt BRUKINSA Once toxicity has resolved to Grade 1 or low…

3 DOSAGE FORMS AND STRENGTHS Capsules: Each 80 mg capsule is a size 0, white to off-white opaque capsule marked with "ZANU 80" in black ink. Tablets: 160 mg, blue, oval, film-coated tablets debossed with "zanu" on one side and functional scoring on the other side. Capsules: 80 mg. ( 3 ) Tablets: 160 mg with functional scoring. ( 3 )

17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Patient Information). Hemorrhage Inform patients to report signs or symptoms of severe bleeding. Inform patients that BRUKINSA may need to be interrupted for major surgeries or procedures [see Warnings and Precautions (5.1) ] .

Infections Inform patients to report signs or symptoms suggestive of infection [see Warnings and Precautions (5.2) ] . Cytopenias Inform patients that they will need periodic blood tests to check blood counts during treatment with BRUKINSA [see Warnings and Precautions (5.3) ] . Second Primary Malignancies Inform patients that other malignancies have been reported in patients who have been treated with BRUKINSA, including skin cancer and other solid tumors.

Advise patients to use sun protection and have monitoring for development of other cancers [see Warnings and Precautions (5.4) ] . Cardiac Arrhythmias Counsel patients to report any signs of palpitations, lightheadedness, dizziness, fainting, shortness of breath, and chest discomfort [see Warnings and Precautions (5.5) ] . Hepatotoxicity, Including Drug-Induced Liver Injury Inform patients that liver problems, including drug-induced liver injury and abnormalities in liver tests, may develop during BRUKINSA treatment.

Advise patients to contact their healthcare provider immediately if they experience abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.6) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential hazard to a fetus and to use effective contraception during treatment and for 1 week after the last dose of BRUKINSA [see Warnings and Precautions (5.7) ] . Advise males with female sexual partners of reproductive potential to use effective contraception during BRUKINSA treatment and for 1 week after the last dose of BRUKINSA [see Use in Specific Populations (8.3) ] .

Lactation Advise females not to breastfeed during treatment with BRUKINSA and for 2 weeks after the last dose [see Use in Specific Populations (8.2) ] . Administration Instructions BRUKINSA capsules may be taken with or without food. Advise patients that BRUKINSA capsules should be swallowed whole with a glass of water and not to open, break, or chew the capsules [see Dosage and Administration (2.1) ] .

BRUKINSA tablets may be taken with or without food. Advise patients that BRUKINSA tablets should be swallowed whole with a glass of water and not to chew or crush the tablets. Tablets can be split in half as prescribed by the healthcare provider [see Dosage and Administration (2.1) ].

Missed Dose Advise patients that if they miss a dose of BRUKINSA, they may still take it as soon as possible on the same day with a return to the normal schedule the following day [see Dosage and Administration (2.1) ] . Drug Interactions Advise patients to inform their healthcare providers of all concomitant medications, including over-the-counter medications, vitamins, and herbal products [see Drug Interactions (7.1) ] .