Zanubrutinib

Indications

Zanubrutinib is used for: Mantel Cell Lymphoma

Adult Dose

Mantel Cell Lymphoma Indicated for mantle cell lymphoma (MCL) in patients who received at least 1 prior therapy 160 mg PO BID or 320 mg PO qDay until disease progression or unacceptable toxicity Hepatic impairment Mild-to-moderate (Child-Pugh A or B): No dosage modification recommended Severe (Child-Pugh C): 80 mg PO BID

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (eCrCl > 30 mL/min): No dosage adjustment necessary Severe (eCrCl <30 mL/min) or on dialysis: Pharmacokinetics of zanubrutinib is unknown; monitor for adverse effects

Administration

May take with or without food Swallow capsules whole with water; do not open, break, or chew capsules

Contra Indications

Precautions

Grade 3 or 4 cytopenias (eg, neutropenia, thrombocytopenia, anemia) reported; monitor CBC counts during treatment and treat using growth factors or transfusions, as needed Second primary malignancies, including nonskin carcinoma, may occur; the most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin); advise to use sun protection Atrial fibrillation and atrial flutter reported; patients with cardiac risk factors, hypertension, and acute infections may be at increased risk; grade ≥3 events reported with monotherapy; monitor for signs and symptoms of atrial fibrillation and atrial flutter and manage as appropriate Infections Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections reported; infections due to hepatitis B virus reactivation have occurred Hemorrhage Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with monotherapy

Pregnancy-Lactation

Pregnancy There are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes Avoid pregnancy during administration; warn patients of the potential hazard to the fetus if used during pregnancy or if patient becomes pregnant while taking zanubrutinib Pregnancy testing is recommended for females of reproductive potential before initiating therapy Animal data Based on findings in animals, fetal harm may occur when administered to a pregnant woman; administration to pregnant rats during organogenesis caused embryofetal toxicity, including malformations, at exposures that were 5 times higher than those reported in patients at recommended dose of 160 mg BID Contraception Females of reproductive potential: Use effective contraception during treatment and for at least 1 week following the last dose Males: Advise men to avoid fathering a child while receiving zanubrutinib and for at least 1 week following the last dose Lactation There are no data on presence of drug or its metabolites in human milk, effects on breastfed child, or on milk production Owing to the potential for serious adverse reactions from therapy in a breastfed child, advise lactating women not to breastfeed during treatment and for at least 2 weeks following last dose

Interactions

Moderate and strong CYP3A4 inhibitors Coadministration with a moderate or strong CYP3A inhibitor increases zanubrutinib plasma levels, which may increase the risk of zanubrutinib toxicities Moderate and strong CYP3A4 inducers Coadministration with a moderate or strong CYP3A inhibitor decreases zanubrutinib plasma levels, which may reduce zanubrutinib efficacy

Side Effects

Side effects of Zanubrutinib : >10% All grades Upper respiratory tract infection (39%) Neutropenia and neutrophil decreased (38-45%) Lymphocytosis (41%) Thrombocytopenia and platelet count decreased (27-40%) Anemia and hemoglobin decreased (14-27%) Rash (36%) Blood uric acid increased (29%) ALT increased (28%) Leukopenia and WBC count decreased (25%) Bilirubin increased (24%) Diarrhea (23%) Pneumonia (15%) Bruising (14%) Hypokalemia (14%) Constipation (13%) Hypertension (12%) Cough (12%) Hemorrhage (11%) Urinary tract infection (11%) Grade >3 Neutropenia and neutrophil decreased (15-20%) Lymphocytosis (16%) 1-10% Hyperuricemia (6%) Headache (4.2%) Grade >3 Pneumonia (10%) Anemia and hemoglobin decreased (6-8%) Thrombocytopenia and platelet count decreased (5-7%) Leukopenia and WBC count decreased (5%) Hypertension (3.4%) Hemorrhage (3.4%) Musculoskeletal pain (3.4%) Blood uric acid increased (2.6%) Hypokalemia (1.7%) <1% Grade >3 ALT increased (0.9%) Bilirubin increased (0.9%) Urinary tract infection (0.8%) Diarrhea (0.8%)

Mode of Action

Bruton tyrosine kinase (BTK) inhibitor 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