Zanubrutinib

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. 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). Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti–CD20-based regimen. Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). 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.

Zanubrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). Zanubrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. In nonclinical studies, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth.

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. Reduce BRUKINSA dose in patients with severe hepatic impairment. Advise patients not to open, break, or chew capsules. Advise patients not to chew or crush tablets. Manage toxicity using treatment interruption, dose reduction, or discontinuation.

None. None.

Hemorrhage: Monitor for bleeding and manage appropriately. Infections: Monitor patients for signs and symptoms of infection, including opportunistic infections, and treat as needed. Cytopenias: Monitor complete blood counts during treatment. Second Primary Malignancies: Other malignancies have developed including skin cancers and non-skin carcinomas. Monitor and advise patients to use sun protection. Cardiac Arrhythmias: Monitor for signs and symptoms of arrhythmias and manage appropriately. Hepatotoxicity, Including Drug-Induced Liver Injury: Monitor hepatic function throughout treatment. Embryo-Fetal Toxicity: Can cause fetal harm. Advise women of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are discussed in more detail in other sections of the labeling: Hemorrhage Infections Cytopenias Second Primary Malignancies Cardiac Arrhythmias Hepatotoxicity, including DILI The most common adverse reactions (≥30%), including laboratory abnormalities, are neutrophil count decreased, platelet count decreased, upper respiratory tract infection, hemorrhage, and musculoskeletal pain.

CYP3A Inhibitors: Modify BRUKINSA dose with moderate or strong CYP3A inhibitors as described. CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).