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- Oncology drug research (https://voice.ons.org/topic/oncology-drug-research)
- U.S. Food and Drug Administration (FDA) (https://voice.ons.org/topic/us-food-and-drug-administration-fda)
- Drug Reference Sheet (https://voice.ons.org/topic/drug-reference-sheet)
Oncology Drug Reference Sheet: Zanubrutinib
Zanubrutinib (BrukinsaTM) received U.S. Food and Drug Administration accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanubrutinib-mantle-cell-lymphoma#:~:text=FDA%20grants%20accelerated%20approval%20to%20zanubrutinib%20for%20mantle%20cell%20lymphoma,-Share&text=On%20November%2014%2C%202019%2C%20the,at%20least%20one%20prior%20therapy.) on November 14, 2019, for the treatment of adult patients with mantle cell lymphoma who have received at least one prior therapy.
A highly selective Bruton tyrosine kinase (TK) inhibitor targeted therapy, zanubrutinib inhibits Bruton TK activation, a signaling molecule of the B-cell antigen receptor and cytokine receptor pathways. Zanubrutinib inhibits malignant B-cell proliferation.
Approved for adult patients with mantle cell lymphoma who have received at least one prior therapy
320 mg per day (4 x 80 mg capsules), administered as 160 mg orally twice daily or 320 mg orally once daily
Orally, swallowed whole with water and with or without food. Do not open, break, or chew capsules.
Myelosuppression may lead to neutropenia, thrombocytopenia, and anemia. Immunosuppression increases risk for opportunitistic infections, including hepatitis B reactivation. Upper respiratory tract infections, cough, rash, and pruritis can also occur. Serious yet rare side effects include pneumonia, hemorrhage, cardiac arrythmias, and secondary malignancies.
A missed dose should be taken as soon as possible on the same day with a return to the normal schedule the following day. Monitor for hemorrhage, infections, cytopenias, second primary malignancies (primarily skin cancer), and cardiac arrhythmias. Consider prophylaxis for herpes simplex virus, pneumocytstis jiroveci pneumomnia, and other infections based on risk.
Zanubrutinib can cause embryo-fetal toxicity when administered to pregnant women. Patients should use reliable contraception while taking the drug and for at least one week after the last dose. Avoid breastfeeding for at least two weeks following the last dose. Modify dosing with moderate or strong CYP3A inhibitors and avoid concomitant use with moderate or strong CYP3A inducers because coadministration of multiple CYP3A inhibitors increases levels of zanubrutinib. A complete drug-drug interaction evaluation, including over-the-counter medications, should be done prior to initiation and routinely throughout therapy.
A patient education sheet is available on oralchemoedsheets.com. Educate patients about the risk of hemorrhage, infections, cytopenias, secondary malignancies, and cardiac arrhythmias. Male and female patients should use reliable birth control while taking zanubrutinib and for at least a week after the last dose. Breastfeeding should be avoided for two weeks after the last dose.
The drug may increase risk of secondary primary malignancies, including skin cancers. Patients should use proper sun protection.
Swallow capsules whole with water. Do not open, break, or chew capsules. Keep out of reach of children and pets. Food and drug interactions can occur, and grapefruit should be avoided. Each dose requires multiple capsules.
No overall differences in safety or effectiveness between younger and older patients were seen in clinical trials. Consider comorbidities in risk assessment for older adults (e.g., cardiac risk factors for arrhythmias).
Zanubrutinib can cause embryo-fetal toxicity and had some morphologic abnormalities in animal tests.