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
Adverse 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%)
Mechanism 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