Version July 2025
Dosage guidance:
Safety: Consider benefit-risk of interrupting zanubrutinib treatment for 3 to 7 days prior to and after surgery (depending on the type of surgery and the risk of bleeding).
Clinical considerations: Consider prophylaxis for herpes simplex virus, Pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients at increased risk for infections.
Chronic lymphocytic leukemia or small lymphocytic lymphoma: Oral: 160 mg twice daily or 320 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Follicular lymphoma, relapsed or refractory: Oral: 160 mg twice daily or 320 mg once daily, in combination with obinutuzumab; continue until disease progression or unacceptable toxicity (Ref).
Mantle cell lymphoma, relapsed or refractory: Oral: 160 mg twice daily or 320 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Marginal zone lymphoma, relapsed or refractory: Oral: 160 mg twice daily or 320 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Waldenström macroglobulinemia: Oral: 160 mg twice daily or 320 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Missed dose: If a dose is missed, it should be administered as soon as possible on the same day and then return to the normal schedule the following day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Kidney function estimated by the Cockcroft-Gault equation.
CrCl ≥15 mL/minute: No dosage adjustment necessary.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
End stage kidney disease on dialysis: There are no dosage adjustments provided in the manufacturer's labeling. Monitor for adverse reactions.
Hepatic impairment prior to treatment:
Mild or moderate impairment (Child-Turcotte-Pugh class A or B): No dosage adjustment necessary. Monitor for adverse reactions.
Severe impairment (Child-Turcotte-Pugh class C): Reduce dose to 80 mg twice daily. Monitor for adverse reactions.
Hepatic impairment during treatment: Drug-induced liver injury: Withhold zanubrutinib if suspected; discontinue zanubrutinib upon confirmation.
Note: Other concomitant anticancer therapies may also require treatment interruption, dosage reduction, and/or discontinuation.
|
Toxicity |
Toxicity occurrence |
Zanubrutinib Dose Modification |
|---|---|---|
|
a Continue zanubrutinib if asymptomatic lymphocytosis occurs in patients with chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL); asymptomatic lymphocytosis should not be considered an adverse reaction in CLL and MCL. Hematologic toxicity may also require growth factor support or transfusions. | ||
|
b Evaluate benefits versus risks before resuming zanubrutinib at the same dose following grade 4 nonhematologic toxicity. | ||
|
Hematologic toxicitiesa | ||
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• Neutropenic fever, grade 3 or 4 • ANC decreased to <500/mm3 lasting >10 consecutive days • Platelet count decreased to 25,000 to 50,000/mm3 with significant bleeding • Platelet count decreased to <25,000/mm3 lasting >10 consecutive days |
First occurrence |
Interrupt zanubrutinib treatment. Once toxicity has resolved to ≤ grade 1 or baseline, resume zanubrutinib at 160 mg twice daily or 320 mg once daily. |
|
Second occurrence |
Interrupt zanubrutinib treatment. Once toxicity has resolved to ≤ grade 1 or baseline, resume zanubrutinib at 80 mg twice daily or 160 mg once daily. | |
|
Third occurrence |
Interrupt zanubrutinib treatment. Once toxicity has resolved to ≤ grade 1 or baseline, resume zanubrutinib at 80 mg once daily. | |
|
Fourth occurrence |
Discontinue zanubrutinib. | |
|
Nonhematologic toxicitiesb | ||
|
Severe or life-threatening |
First occurrence |
Interrupt zanubrutinib treatment. Once toxicity has resolved to ≤ grade 1 or baseline, resume zanubrutinib at 160 mg twice daily or 320 mg once daily. |
|
Second occurrence |
Interrupt zanubrutinib treatment. Once toxicity has resolved to ≤ grade 1 or baseline, resume zanubrutinib at 80 mg twice daily or 160 mg once daily. | |
|
Third occurrence |
Interrupt zanubrutinib treatment. Once toxicity has resolved to ≤ grade 1 or baseline, resume zanubrutinib at 80 mg once daily. | |
|
Fourth occurrence |
Discontinue zanubrutinib. | |
|
Cardiac arrhythmias |
Manage appropriately as clinically indicated. Consider the risks/benefits of continued zanubrutinib treatment. | |
|
Infection |
Manage appropriately. | |
|
Intracranial hemorrhage (any grade) |
Discontinue zanubrutinib. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypertension (14% to 19%), peripheral edema (12%)
Dermatologic: Pruritus (6% to 11%), skin rash (20% to 29%)
Endocrine & metabolic: Decreased serum calcium (21% to 27%), decreased serum phosphate (20% to 21%), hypermagnesemia (22%), increased serum glucose (45% to 55%), increased serum potassium (24%), increased uric acid (16%)
Gastrointestinal: Constipation (6% to 16%), diarrhea (14% to 22%; grades 3/4: ≤3%), nausea (10% to 18%), vomiting (12%)
Genitourinary: Urinary tract infection (7% to 11%)
Hematologic & oncologic: Bruise (16% to 24%), decreased hemoglobin (20% to 29%; grades 3/4: 3% to 7%), decreased neutrophils (37% to 50%; grades 3/4: 15% to 24%), decreased platelet count (22% to 35%; grades 3/4: 2% to 8%), hemorrhage (including gastrointestinal hemorrhage, hematoma, hemothorax, intracranial hemorrhage: 24% to 42%; grades 3/4: 3% to 4%), leukocytosis (21%; grades 3/4: 21%), lymphocytosis (24%; grades 3/4: 19%), second primary malignant neoplasm (13%; including hematologic malignancy, malignant melanoma, malignant solid tumor, skin carcinoma)
Hepatic: Increased serum alanine aminotransferase (21%), increased serum bilirubin (12%)
Nervous system: Dizziness (10% to 13%), fatigue (13% to 31%), headache (8% to 18%)
Neuromuscular & skeletal: Musculoskeletal pain (26% to 45%)
Renal: Increased serum creatinine (22% to 31%)
Respiratory: Cough (11% to 16%), dyspnea (14%), pneumonia (12% to 18%), upper respiratory tract infection (27% to 44%)
Miscellaneous: Fever (16%)
1% to 10%:
Cardiovascular: Atrial fibrillation (≤5%), atrial flutter (≤5%), edema (5% to 8%), supraventricular cardiac arrhythmia (9%)
Gastrointestinal: Abdominal pain (8%)
Genitourinary: Hematuria (<10%)
Hematologic & oncologic: Febrile neutropenia (3%)
Infection: Influenza (3%)
Local: Localized infection (<10%)
Neuromuscular & skeletal: Muscle spasm (10%)
Frequency not defined:
Cardiovascular: Ventricular arrhythmia (grades ≥3)
Hematologic & oncologic: Petechia, purpuric disease
Hepatic: Exacerbation of hepatitis B
Infection: Infection (grades ≥3: including bacterial infection, fungal infection, opportunistic infection, serious infection, viral infection)
Postmarketing: Hepatic: Hepatotoxicity
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to zanubrutinib or any component of the formulation.
Concerns related to adverse effects:
• Cardiovascular effects: Serious cardiac arrhythmias have occurred in patients treated with zanubrutinib. Atrial fibrillation, atrial flutter, and ventricular arrhythmias have occurred in a small percentage of patients who received zanubrutinib; ≥ grade 3 events were reported rarely. Signs/symptoms of cardiac arrhythmias include palpitations, dizziness, syncope, dyspnea, and/or chest discomfort. Patients with cardiac risk factors, hypertension, and/or acute infections may be at increased risk.
• Hematologic effects: Grade 3 or 4 cytopenias (including neutropenia, thrombocytopenia, and anemia) have been reported with zanubrutinib.
• Hemorrhage: Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with zanubrutinib. Grade 3 or higher hemorrhage (including intracranial and GI hemorrhage, hematuria, and hemothorax) have been reported in a small percentage of patients. Nearly one-third of the patients who received zanubrutinib experienced hemorrhage of any grade, excluding purpura and petechiae. Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Concurrent administration of zanubrutinib with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.
• Hepatotoxicity: Hepatotoxicity, including severe, life-threatening, and potentially fatal drug-induced liver injury, has occurred with zanubrutinib.
• Infection: Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with zanubrutinib. Grade 3 or higher infections have occurred; pneumonia was the most common ≥ grade 3 infection. Infections due to hepatitis B virus reactivation have also occurred.
• Secondary malignancies: Second primary malignancies, including nonskin carcinoma, have occurred with zanubrutinib. The most frequent second primary malignancy was nonmelanoma skin cancer; other reported malignancies included other solid tumors (including melanoma) and hematologic malignancies. Advise patients to use sun protection.
Special populations:
• Older adults: Patients ≥65 years of age experienced higher numbers of grade 3 or higher and serious adverse reactions (compared to patients <65 years of age).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Brukinsa: 80 mg
No
Capsules (Brukinsa Oral)
80 mg (per each): $157.44
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Brukinsa: 80 mg
Available through specialty pharmacies and distributors. Information regarding distribution is available from the manufacturer at https://www.brukinsa.com/ordering-information-and-distribution-sheet.pdf.
Oral: Administer with or without food. Swallow capsules whole with water; do not open, break, or chew capsules.
Chronic lymphocytic leukemia or small lymphocytic lymphoma: Treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma in adults.
Follicular lymphoma, relapsed or refractory: Treatment (in combination with obinutuzumab) of relapsed or refractory follicular lymphoma in adults after ≥2 lines of systemic therapy.
Mantle cell lymphoma, relapsed or refractory: Treatment of mantle cell lymphoma in adults who have received at least 1 prior therapy.
Marginal zone lymphoma, relapsed or refractory: Treatment of relapsed or refractory marginal zone lymphoma in adults who have received at least 1 anti–CD20-based regimen.
Waldenström macroglobulinemia: Treatment of Waldenström macroglobulinemia in adults.
Brukinsa may be confused with Imbruvica.
Zanubrutinib may be confused with acalabrutinib, ibrutinib, pirtobrutinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2C19 (Weak), CYP3A4 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Agents with Antiplatelet Effects: Zanubrutinib may increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Anticoagulants: Zanubrutinib may increase adverse/toxic effects of Anticoagulants. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Atogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clarithromycin: May increase serum concentration of Zanubrutinib. Management: Reduce the dose of zanubrutinib to 80 mg twice daily during coadministration with clarithromycin 250 mg twice daily. Reduce the dose of zanubrutinib to 80 mg once daily with clarithromycin 500 mg twice daily. Risk D: Consider Therapy Modification
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Zanubrutinib. Management: Avoid this combination if possible. If coadministration of zanubrutinib and a moderate CYP3A4 inducer is required, increase the zanubrutinib dose to 320 mg twice daily. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Strong): May decrease serum concentration of Zanubrutinib. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg twice daily during coadministration with a moderate CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Zanubrutinib. Management: Decrease the zanubrutinib dose to 80 mg once daily during coadministration with a strong CYP3A4 inhibitor. Further dose adjustments may be required for zanubrutinib toxicities, refer to prescribing information for details. Risk D: Consider Therapy Modification
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Digoxin: Zanubrutinib may increase serum concentration of Digoxin. Risk C: Monitor
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Zanubrutinib. Management: Avoid consumption of grapefruit juice, a moderate CYP3A4 inhibitor, with zanubrutinib whenever possible. Because grapefruit juice consumption is highly variable, typical dose adjustments associated with moderate CYP3A4 inhibitors are not likely feasible. Risk D: Consider Therapy Modification
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
NiMODipine: CYP3A4 Inducers (Weak) may decrease serum concentration of NiMODipine. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Posaconazole: May increase serum concentration of Zanubrutinib. Management: Reduce the dose of zanubrutinib to 80 mg twice daily during coadministration with posaconazole suspension 100 mg once daily. Reduce the dose of zanubrutinib to 80 mg once daily with higher doses of posaconazole (eg, 300 mg daily). Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Selpercatinib: CYP3A4 Inducers (Weak) may decrease serum concentration of Selpercatinib. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Therapeutic Antiplatelets: Zanubrutinib may increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Ubrogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider Therapy Modification
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 1 week after the last zanubrutinib dose. Patients with partners who could become pregnant should use effective contraception during therapy and for 1 week after the last zanubrutinib dose.
Based on data from animal reproduction studies, in utero exposure to zanubrutinib may cause fetal harm.
It is not known if zanubrutinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy or for 2 weeks following the last zanubrutinib dose.
Avoid grapefruit, grapefruit juice, and Seville oranges during therapy.
Monitor CBC regularly during treatment. Monitor bilirubin and transaminases at baseline and periodically during treatment; monitor more frequently in patients with abnormal liver tests or signs/symptoms of toxicity. Evaluate pregnancy status prior to use (in patients who could become pregnant). Monitor for signs/symptoms of cardiac arrhythmias (eg, palpitations, dizziness, syncope, dyspnea, chest discomfort), bleeding, and/or fever or other signs/symptoms of infection. Monitor for toxicities in patients with severe kidney impairment (or on dialysis). Monitor for second primary malignancies. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Assess BP at baseline and each clinical visit (as well as weekly home monitoring for initial 3 months), obtain ECG at each clinical visit, obtain a baseline echocardiography (transthoracic preferred) in high-risk patients; echocardiography is also recommended in all patients who develop atrial fibrillation (ESC [Lyon 2022]).
Zanubrutinib is a highly selective Bruton tyrosine kinase (BTK) inhibitor (Tam 2019; Tam 2020). Zanubrutinib forms a covalent bond with a cysteine residue in the BTK active site to inhibit BTK activity. BTK is a signaling molecule of the B-cell antigen receptor and cytokine receptor pathways. BTK signals activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. Zanubrutinib inhibits malignant B-cell proliferation and reduces tumor growth.
Distribution: Vz/F: 537 L.
Protein binding: ~94%.
Metabolism: Hepatic; primarily via CYP3A.
Half-life elimination: ~2 to 4 hours.
Time to peak: 2 hours.
Excretion: Feces: ~87% (38% as unchanged drug); urine: ~8% (<1% as unchanged drug).
Clearance: 128 L/hour.
Hepatic function impairment: Zanubrutinib total AUC increased by 11% in subjects with mild impairment (Child-Turcotte-Pugh Class A), by 21% in subjects with moderate impairment (Child-Turcotte-Pugh Class B), and by 60% in subjects with severe impairment (Child-Turcotte-Pugh Class C), compared to subjects with normal hepatic function. Zanubrutinib unbound AUC increased by 23%, 43%, and 194% in subjects with mild, moderate, and severe impairment, respectively, compared to subjects with normal hepatic function.
