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Zanubrutinib: Drug information

Zanubrutinib: Drug information
(For additional information see "Zanubrutinib: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Brukinsa
Brand Names: Canada
  • Brukinsa
Pharmacologic Category
  • Antineoplastic Agent;
  • Antineoplastic Agent, Bruton Tyrosine Kinase Inhibitor;
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor
Dosing: Adult

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

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

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

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.

Dosing: Kidney Impairment: Adult

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.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Usual zanubrutinib starting dose: 160 mg twice daily or 320 mg once daily.

Zanubrutinib Dosage Modifications for Adverse Reactions

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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Brukinsa: 80 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Brukinsa: 80 mg

Prescribing and Access Restrictions

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.

Administration: Adult

Oral: Administer with or without food. Swallow capsules whole with water; do not open, break, or chew capsules.

Use: Labeled Indications

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.

Medication Safety Issues
Sound-alike/look-alike issues:

Brukinsa may be confused with Imbruvica.

Zanubrutinib may be confused with acalabrutinib, ibrutinib.

High alert medication:

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.

Adverse Reactions

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

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to zanubrutinib or any component of the formulation.

Warnings/Precautions

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.

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP2C19 (weak), CYP3A4 (weak)

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). 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: 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). 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

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Digoxin: Zanubrutinib may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). 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

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 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

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/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). 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

Reproductive Considerations

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.

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to zanubrutinib may cause fetal harm.

Breastfeeding Considerations

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.

Dietary Considerations

Avoid grapefruit, grapefruit juice, and Seville oranges during therapy.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics

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.

Pharmacokinetics: Additional Considerations

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.

Pricing: US

Capsules (Brukinsa Oral)

80 mg (per each): $139.97

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.

  1. Brukinsa (zanubrutinib) [prescribing information]. San Mateo, CA: BeiGene USA Inc; June 2022.
  2. Brukinsa (zanubrutinib) [product monograph]. Milton, Ontario, Canada: Innomar Strategies Inc; February 2022.
  3. Dimopoulos M, Sanz RG, Lee HP, et al. Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial. Blood Adv. 2020;4(23):6009-6018. doi:10.2337/dci18-0033 [PubMed 33284944]
  4. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  5. Opat S, Tedeschi A, Linton K, et al. The MAGNOLIA trial: zanubrutinib, a next-generation bruton tyrosine kinase inhibitor, demonstrates safety and efficacy in relapsed/refractory marginal zone lymphoma. Clin Cancer Res. 2021;27(23):6323-6332. doi:10.1158/1078-0432.CCR-21-1704 [PubMed 34526366]
  6. Song Y, Zhou K, Zou D, et al. Treatment of patients with relapsed or refractory mantle-cell lymphoma with zanubrutinib, a selective inhibitor of Bruton's tyrosine kinase. Clin Cancer Res. 2020;26(16):4216-4224. doi:10.1158/1078-0432.CCR-19-3703 [PubMed 32461234]
  7. Tam CS, Opat S, D'Sa S, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020;136(18):2038-2050. doi:10.1182/blood.2020006844 [PubMed 32731259]
  8. Tam CS, Trotman J, Opat S, et al. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019;134(11):851-859. [PubMed 31340982]
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