BRUKINSA
Clinical safety rating
cautionComprehensive clinical and safety monograph for BRUKINSA (BRUKINSA).
Comprehensive clinical and safety monograph for BRUKINSA (BRUKINSA).
Mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapyWaldenström's macroglobulinemia (WM) in adult patientsRelapsed or refractory marginal zone lymphoma (MZL) in adult patients who have received at least one prior anti-CD20-based regimenChronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients
Zanubrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with the cysteine residue at position 481 in the BTK active site, leading to sustained inhibition of BTK activity. This blocks B-cell receptor (BCR) signaling, thereby inhibiting the proliferation, migration, and survival of malignant B cells.
| Metabolism | Zanubrutinib is primarily metabolized by cytochrome P450 3A4 (CYP3A4). Following oral administration, it undergoes oxidation and further phase II metabolism. The major circulating metabolite is a product of CYP3A4-mediated oxidation. |
| Excretion | Biliary/fecal (87% as unchanged drug), renal (8% as unchanged drug) |
| Half-life | 4 hours (terminal), supports twice-daily dosing |
| Protein binding | 96% bound to plasma proteins (mainly albumin) |
| Volume of Distribution | 3.23 L/kg (central Vd), indicating extensive tissue distribution |
| Bioavailability | Oral: 48% under fasting conditions; high-fat meal decreases AUC by 30% |
| Onset of Action | Oral: measurable BTK occupancy within 4 hours; clinical response onset within weeks |
| Duration of Action | BTK occupancy > 90% sustained over 12-hour dosing interval; clinical duration per cycle |
| Molecular Weight | 471.6 |
320 mg orally once daily or 160 mg orally twice daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for CrCl ≥30 mL/min. For CrCl <30 mL/min, reduce dose to 80 mg twice daily. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 80 mg twice daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established; no approved dosing. |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity due to age-related renal/hepatic decline. |
| 1st trimester | Avoid. Zanubrutinib is a BTK inhibitor; animal studies show embryofetal toxicity and teratogenicity. No adequate human data. |
| 2nd trimester | Avoid. Same risks as T1; potential for fetal harm. |
| 3rd trimester | Avoid. Risk of fetal harm and potential adverse effects on hematopoietic system. |
Clinical note
Comprehensive clinical and safety monograph for BRUKINSA (BRUKINSA).
| Placental transfer | Expected to cross placenta based on molecular weight (<500 Da) and animal studies showing fetal distribution. |
| Breastfeeding | No data on presence in human milk. Due to potential for serious adverse reactions in breastfed infant, advise against breastfeeding during treatment and for at least 2 weeks after last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Based on animal studies and mechanism of action (BTK inhibitor), BRUKINSA (zanubrutinib) can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, administration of zanubrutinib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity including increased post-implantation loss, reduced fetal body weights, and increased incidence of skeletal variations at exposures less than or equal to human clinical exposure at the recommended dose of 320 mg daily. Therefore, avoid use during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus. If used, advise pregnant women of the potential risk to the fetus. |
| Fetal Monitoring | Monitor pregnancy status prior to initiation of BRUKINSA. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 week after the last dose. If a patient becomes pregnant while taking BRUKINSA, monitor for maternal toxicities including neutropenia, thrombocytopenia, and hemorrhage. Perform complete blood counts regularly throughout pregnancy. Fetal monitoring by ultrasonography should be considered to assess for growth abnormalities because of the potential for fetal harm. |
| Fertility Effects | Based on animal studies, BRUKINSA may impair fertility in females of reproductive potential. In female rats, zanubrutinib caused disruption of the estrous cycle and decreased fertility at exposures less than the human clinical exposure. No specific fertility studies in humans have been conducted. For male patients, there are no data on effects on spermatogenesis or fertility. Advise patients that BRUKINSA may impair fertility. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to zanubrutinib or any excipients
| Precautions | Hemorrhage: Serious and fatal hemorrhagic events may occur. Monitor for signs of bleeding. Consider benefit-risk in patients requiring antiplatelet or anticoagulant therapy., Infections: Fatal and serious infections (including pneumonia, sepsis) have occurred. Monitor for signs of infection and manage promptly., Cytopenias: Neutropenia, thrombocytopenia, and anemia may occur. Monitor blood counts regularly., Cardiac arrhythmias: Atrial fibrillation and atrial flutter have been reported. Monitor for symptoms of arrhythmia and manage appropriately., Second primary malignancies: Including non-melanoma skin cancer, have been reported. Advise patients to use sun protection., Tumor lysis syndrome: Can occur. Assess risk and monitor patients appropriately. |
| Food/Dietary | Avoid grapefruit products and Seville oranges. No significant food effect on absorption; may be taken with or without food. |
| Clinical Pearls | Monitor for atrial fibrillation/flutter and hemorrhage; baseline ECG recommended. Dose adjust for severe hepatic impairment (Child-Pugh C). Avoid strong or moderate CYP3A inhibitors/inducers; use with caution in patients requiring antiplatelet or anticoagulant therapy. |
| Patient Advice | Take BRUKINSA with or without food, but avoid grapefruit and Seville oranges. · Swallow capsules whole; do not crush or chew. · Inform your doctor of any bleeding or bruising, irregular heartbeat, or signs of infection. · Do not use antacids, proton pump inhibitors, or histamine-2 blockers without consulting your doctor. · If you miss a dose, take it as soon as remembered unless it is less than 12 hours until the next dose; then skip the missed dose. |
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