Most recent update(s): The National Institute of Health’s COVID-19 guidelines recommend against the use of Bruton tyrosine kinase inhibitors, such as zanubrutinib, for the treatment of COVID-19, except in a clinical trial.
As part of our response to the evolving COVID-19 pandemic, published literature and guidelines from major health organizations are continuously monitored for potential content updates. At this time, only investigational medications with data determined to be of relatively high quality and/or consistently showing positive clinical outcomes to support dosing recommendations will be included in the Lexicomp monograph, outside of this Special Alert field.
Further information may be found at:
IDSA: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
ClinicalTrials.gov: https://clinicaltrials.gov/ct2/results?cond=Covid19&term=zanubrutinib&cntry=&state=&city=&dist=
Note: Consider prophylaxis for herpes simplex virus, Pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients at increased risk for infections. 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).
Mantle cell lymphoma, relapsed or refractory: Oral: 160 mg twice daily (Song 2020) or 320 mg once daily until disease progression or unacceptable toxicity.
Marginal zone lymphoma, relapsed or refractory: Oral: 160 mg twice daily (Opat 2021) or 320 mg once daily until disease progression or unacceptable toxicity.
Waldenström macroglobulinemia: Oral: 160 mg twice daily (Dimopoulos 2020; Tam 2020) or 320 mg once daily until disease progression or unacceptable toxicity.
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 renal disease on dialysis: There are no dosage adjustments provided in the manufacturer's labeling. Monitor for adverse reactions.
Mild or moderate impairment (Child-Pugh Class A or B): No dosage adjustment necessary. Monitor for adverse reactions.
Severe impairment (Child-Pugh Class C): Reduce dose to 80 mg twice daily. Monitor for adverse reactions.
Refer to adult dosing.
Usual zanubrutinib starting dose: 160 mg twice daily or 320 mg once daily.
Toxicity |
Toxicity occurrence |
Zanubrutinib Dose Modification |
---|---|---|
a Continue zanubrutinib if asymptomatic lymphocytosis occurs (asymptomatic lymphocytosis should not be considered an adverse reaction). 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. | ||
Hematologica or nonhematologic (grade 3 or 4) toxicities: • Neutropenic fever, grade 3 • Neutropenia, grade 4 (lasting >10 consecutive days) • Thrombocytopenia, grade 3 with significant bleeding • Thrombocytopenia, grade 4 (lasting >10 consecutive days) • Nonhematologic toxicity, grade 3 or 4b |
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. | |
Atrial fibrillation or atrial flutter |
Manage as clinically indicated. | |
Infection |
Manage appropriately. | |
Intracranial hemorrhage (any grade) |
Discontinue zanubrutinib. |
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Brukinsa: 80 mg
No
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.
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.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Hypertension (12% to 14%), peripheral edema (12%)
Dermatologic: Pruritus (11%), skin rash (21% to 36%)
Endocrine & metabolic: Decreased serum calcium (23% to 27%), decreased serum phosphate (20% to 27%), hypokalemia (14%), increased serum glucose (45% to 54%), increased serum potassium (24%)
Gastrointestinal: Abdominal pain (14%), constipation (13% to 16%), diarrhea (22% to 25%; grade 3/4: <3%), nausea (13% to 18%), vomiting (12%)
Genitourinary: Urinary tract infection (11%)
Hematologic & oncologic: Anemia (14% to 27%; grades 3/4: 6% to 8%), bruise (14% to 24%), hemorrhage (including hematoma: 11% to 42%; grades 3/4: 1% to 5%), leukopenia (25%; grades ≥3: 5%), lymphocytopenia (31% to 32%; grade 3/4: 8%), lymphocytosis (41%; grades 3/4: 16%), neutropenia (38% to 54%; grades 3/4: 13% to 26%), second primary malignant neoplasm (14%), thrombocytopenia (27% to 41%; grades 3/4: 4% to 11%)
Hepatic: Increased serum alanine aminotransferase (22% to 28%), increased serum bilirubin (12% to 24%)
Infection: Infection (grades ≥3: ≤27%, including bacterial infection, fungal infection, opportunistic infection, serious infection, viral infection)
Nervous system: Dizziness (13%), fatigue (21% to 31%), headache (4% to 18%)
Neuromuscular & skeletal: Musculoskeletal pain (14% to 45%)
Renal: Increased serum creatinine (31% to 34%)
Respiratory: Cough (10% to 16%), dyspnea (14%), pneumonia (4% to 15%), upper respiratory tract infection (26% to 47%)
Miscellaneous: Fever (16%)
1% to 10%:
Cardiovascular: Atrial fibrillation (≤3%), atrial flutter (≤3%), edema (<10%)
Endocrine & metabolic: Hyperuricemia (6%)
Gastrointestinal: Gastrointestinal hemorrhage (grades ≥3: ≤3%)
Genitourinary: Hematuria (<10%)
Hematologic & oncologic: Febrile neutropenia (3%), hematologic disease (malignancy: 1%), malignant melanoma (2%), malignant solid tumor (4%), petechia (<10%), purpuric disease (<10%), skin carcinoma (non-melanoma: 8%)
Infection: Influenza (3%)
Nervous system: Intracranial hemorrhage (≤3%), peripheral neuropathy (<10%)
Neuromuscular & skeletal: Muscle spasm (10%)
Respiratory: Hemothorax (grades ≥3: ≤3%)
<1%: Hepatic: Exacerbation of hepatitis B
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: Atrial fibrillation and atrial flutter have occurred in a small percentage of patients who received zanubrutinib as a single agent; ≥ grade 3 events were reported rarely. 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 single-agent zanubrutinib.
• Hemorrhage: Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with zanubrutinib (as a single agent). Grade 3 or higher hemorrhage (including intracranial and GI hemorrhage, hematuria, and hemothorax) have been reported in a small percentage of patients. Approximately one-third of the patients who received zanubrutinib monotherapy 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.
• Infection: Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with zanubrutinib monotherapy. 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 monotherapy. The most frequent second primary malignancy was nonmelanoma skin cancer; other reported malignancies included melanoma, malignant solid tumors, and hematologic malignancies. Advise patients to use sun protection.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2C19 (weak), CYP3A4 (weak)
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Zanubrutinib may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anticoagulants: Zanubrutinib may enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Zanubrutinib. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Zanubrutinib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the 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 the 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
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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
Digoxin: Zanubrutinib may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such as the oncology agents listed in this monograph. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Risk D: Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the 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 enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect 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
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease the serum concentration of Sirolimus (Protein Bound). Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inducers (Weak) may decrease the 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 enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who can become pregnant. Patients who may become pregnant should use effective contraception during therapy and for 1 week after the last zanubrutinib dose. Patients with partners who can 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. Evaluate pregnancy status prior to use (in patients who can become pregnant). Monitor for signs/symptoms of atrial fibrillation/atrial flutter, bleeding, and/or fever or other signs/symptoms of infection. Monitor for toxicities in patients with hepatic impairment or severe renal 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.
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-Pugh Class A), by 21% in subjects with moderate impairment (Child-Pugh Class B), and by 60% in subjects with severe impairment (Child-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.
Capsules (Brukinsa Oral)
80 mg (per each): $139.97
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