BRUKINSA

Small Molecule Antineoplastic Bruton's Tyrosine Kinase (BTK) Inhibitors

Emetic Risk
Minimal/Low
Administer prn antiemetics as necessary.

Oral Administration Oral Solid Formulations

Take zanubrutinib orally with or without food.
Swallow capsules whole with water; do not open, break, or chew capsules.
If a dose is missed, take it as soon as possible on the same day and then return to the regular schedule the next day.

Severe

infection / Delayed / 0-24.0
neutropenia / Delayed / 22.0-22.0
leukocytosis / Delayed / 0-21.0
lymphocytosis / Delayed / 0-19.0
new primary malignancy / Delayed / 13.0-13.0
hypertension / Early / 3.4-13.0
musculoskeletal pain / Early / 0-9.0
lymphopenia / Delayed / 0-8.0
thrombocytopenia / Delayed / 8.0-8.0
fever / Early / 0-8.0
anemia / Delayed / 7.0-7.0
skin cancer / Delayed / 1.2-7.0
bleeding / Early / 3.6-3.6
diarrhea / Early / 0-3.4
hyperuricemia / Delayed / 0-3.2
hypophosphatemia / Delayed / 0-3.1
abdominal pain / Early / 0-2.3
fatigue / Early / 0-2.3
elevated hepatic enzymes / Delayed / 0-2.1
hypocalcemia / Delayed / 0-2.0
hyperkalemia / Delayed / 0-2.0
headache / Early / 0-1.8
atrial fibrillation / Early / 1.7-1.7
atrial flutter / Early / 1.7-1.7
rash / Early / 0-1.3
nephrotoxicity / Delayed / 0-1.1
pruritus / Rapid / 0-1.0
dizziness / Early / 0-1.0
hyperbilirubinemia / Delayed / 0-1.0
constipation / Delayed / 0-0.4
cough / Delayed / 0-0.3
intracranial bleeding / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
renal failure / Delayed / Incidence not known
aortic dissection / Delayed / Incidence not known

Moderate

hyperglycemia / Delayed / 0-49.4
hypermagnesemia / Delayed / 0-31.0
dyspnea / Early / 0-14.0
peripheral edema / Delayed / 0-12.0
edema / Delayed / 0-10.0
peripheral neuropathy / Delayed / 0-10.0
hemoptysis / Delayed / Incidence not known
postmenopausal bleeding / Delayed / Incidence not known
melena / Delayed / Incidence not known
cystitis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
erythema / Early / Incidence not known
atopic dermatitis / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
bone pain / Delayed / Incidence not known

Mild

nausea / Early / 0-18.0
vomiting / Early / 0-12.0
purpura / Delayed / 0-10.0
petechiae / Delayed / 0-10.0
muscle cramps / Delayed / 0-10.0
influenza / Delayed / 0-3.0
ecchymosis / Delayed / Incidence not known
epistaxis / Delayed / Incidence not known
rhinitis / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
laryngitis / Delayed / Incidence not known
sinusitis / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
maculopapular rash / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
back pain / Delayed / Incidence not known
myalgia / Early / Incidence not known
arthralgia / Delayed / Incidence not known
lethargy / Early / Incidence not known
asthenia / Delayed / Incidence not known
vertigo / Early / Incidence not known

BRUKINSA

Rx

An oral Bruton tyrosine kinase (BTK) inhibitor
Used for chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenstrom macroglobulinemia, and certain types of mantle cell lymphoma and marginal zone lymphoma
Fatal and serious bleeding events have been reported

For the treatment of mantle cell lymphoma (MCL).
NOTE: Zanubrutinib has been designated as an orphan drug by the FDA for the treatment of MCL.
For the treatment of MCL in patients who have received at least 1 prior therapy. Oral dosage Adults

160 mg orally twice daily OR 320 mg orally once daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, dose reduction, and/or discontinuation may be necessary if severe toxicity occurs. The independent review committee (IRC)-assessed overall response rate (ORR) was 84% (complete response rate (CR), 59%) in patients with mantle cell lymphoma who received zanubrutinib in an open-label, phase 2 trial (n = 86; Trial LY-004). The median duration of response (DOR) was 19.5 months. Patients (median age, 60.5 years; range, 34 to 75 years) in this trial had received a median of 2 prior treatments (range, 1 to 4). Additionally, the IRC-assessed ORR was 84.4% (CR, 25%) in patients (median age, 70.5 years; range, 42 to 86 years) with relapsed or refractory mantle cell lymphoma who received zanubrutinib in an open-label, phase 1/2 trial (n = 32). At a median follow-up off 18.8 months, the median DOR was 18.5 months and the median progression-free survival was 21.1 months.

For the treatment of Waldenstrom macroglobulinemia.
NOTE: Zanubrutinib has been designated as an orphan drug by the FDA for the treatment of Waldenstrom macroglobulinemia.
Oral dosage Adults

160 mg orally twice daily OR 320 mg orally once daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, dose reduction, and/or discontinuation may be necessary if severe toxicity occurs. The independent review committee-assessed complete response (CR) or very good partial response (VGPR) rates (assessed using the standard IWWM-6 criteria) were 15.7% and 7.1% in patients with MYD88 L265P mutation Waldenstrom macroglobulinemia who received zanubrutinib 160 mg PO twice daily (n = 102) and ibrutinib 420 mg PO once daily (n = 99), respectively, in cohort 1 of a randomized, 2-cohort, phase 3 (ASPEN) trial. No patient experienced a CR. The overall response (ORR: CR + VGPR + partial response) rates were 77.5% and 77.8% in the zanubrutinib and ibrutinib arms, respectively. In cohort 1, 82% of patients had relapsed or refractory disease; these patients had received a median of 1 prior therapy (range, 1 to 8 therapies). The ORR was 50% in patients with MYD88 wild type Waldenstrom macroglobulinemia who received zanubrutinib in cohort 2 (n = 26). Most patients in cohort 2 (89%) had relapsed or refractory disease.

For the treatment of marginal zone lymphoma. For the treatment of relapsed or refractory marginal zone lymphoma (MZL) in patients who have received at least 1 anti-CD20-based regimen.
NOTE: Zanubrutinib has been designated as an orphan drug by the FDA for the treatment of splenic MZL, extranodal MZL of mucosa-associated lymphoid tissue, and nodal MZL.
Oral dosage Adults

160 mg orally twice daily OR 320 mg orally once daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, dose reduction, and/or discontinuation may be necessary if severe toxicity occurs. The independent review committee (IRC)-assessed overall response rate (ORR) was 56% (complete response rate (CR), 59%) in patients with relapsed or refractory MZL who received zanubrutinib 160 mg twice daily in an open-label, phase 2 trial (n = 66; Trial BGB-311-214). At an estimated median follow-up time of 8.3 months, the duration of response (DOR) was not estimable. Patients (median age, 70 years; range, 37 to 85 years) in this trial had received a median of 2 prior treatments (range, 1 to 16). All patients received at least 1 prior anti-CD20-based regimen; 88% of patients had received prior rituximab-based therapy. Additionally, the IRC-assessed ORR was 80% (CR, 20%) in patients (median age, 70 years; range, 52 to 85 years) with relapsed or refractory MZL who received zanubrutinib (n = 20) in an open-label, phase 1/2 trial. At an estimated median follow-up time of 31.4 months, the median DOR was not estimable.

For the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
NOTE: Zanubrutinib has been designated by the FDA as an orphan drug for the treatment of CLL.
Oral dosage Adults

160 mg orally twice daily OR 320 mg orally once daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, dose reduction, and/or discontinuation may be necessary if severe toxicity occurs. Zanubrutinib was evaluated in patients (median age, 70 years) with previously untreated CLL or SLL (8.6%) who were aged 65 years and older or 18 years or older with comorbidities in a multinational, phase 3 (SEQUOIA) trial (n = 590). In cohort 1, patients without del(17)(p13.1) were randomized (1:1) to zanubrutinib (group A; n = 241) or bendamustine plus rituximab (group B; n = 238). Cohort 2 consisted of patients with del(17)(p13.1) who received zanubrutinib (group C; n = 111). The median progression-free survival (PFS) time was significantly improved with zanubrutinib compared with bendamustine and rituximab therapy (median time not reached in either arm; hazard ratio (HR) = 0.42; 95% CI, 0.28 to 0.63) at a prespecified interim analysis (median follow-up time, 26.2 months). At the time of this analysis, there was no significant difference in overall survival (OS) between groups A and B (HR = 1.07, 95% CI, 0.51 to 2.22). At a median follow-up of 30.5 months, the median PFS time had not been reached in patients who received zanubrutinib in group C. In patients who received zanubrutinib in this trial, the estimated 24-month PFS and OS rates were 85.5% and 94.3%, respectively, in group A and 88.9% and 93.6%, respectively, in group C. Investigator-assessed overall response rate (ORR) was significantly improved with zanubrutinib compared with ibrutinib (78.3% vs. 62.5%; p-value less than 0.001) in patients with relapsed or refractory CLL or SLL in a preplanned interim analysis (median follow-up time, 15.3 [0.1 to 26] months) of a multinational, randomized, phase 3 (ALPINE) trial. However, response noninferiority but not superiority was determined by a blinded independent central review (ICR). At a median follow-up of 29.6 months, the investigator- (83.5% vs. 74.2%) and ICR- (86.2% vs. 75.7%) assessed ORR were numerically higher with zanubrutinib compared with ibrutinib therapy in the ALPINE trial (n = 652). The investigator-assessed median PFS times were significantly longer in the zanubrutinib compared with the ibrutinib arm (median not reached vs. 34.2 months; HR = 0.65; 95% CI, 0.49 to 0.86; p = 0.002). Patients (67 [range, 35 to 90] years) in this trial had received a median of 1 (range, 1 to 12) prior line of therapy; 14.5% of patients had chromosome 17p deletion.

Hepatic Impairment

Mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment: No initial dosage adjustment is necessary.Severe hepatic impairment (Child-Pugh class C): Reduce the initial dose to 80 mg PO twice daily.

Renal Impairment

Mild, moderate, or severe renal impairment (creatinine clearance of 15 mL/min or higher): No initial dosage adjustment is necessary.

Adagrasib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with adagrasib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of adagrasib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A inhibitor.
Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with zanubrutinib is necessary. If zanubrutinib is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak CYP3A4 inducer like zanubrutinib with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Amiodarone: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with amiodarone. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of amiodarone, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; amiodarone is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Amobarbital: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with clarithromycin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of clarithromycin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 183% when coadministered with clarithromycin.
Apalutamide: (Major) Avoid the concomitant use of zanubrutinib and apalutamide. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; apalutamide is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Aprepitant, Fosaprepitant: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with a multi-day regimen of aprepitant. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of aprepitant, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; aprepitant is a moderate CYP3A4 inhibitor when administered as a 3-day regimen and a weak inhibitor when given as a single dose. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions; it is also a weak CYP3A4 inhibitor when administered as a single dose. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Atazanavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with atazanavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of atazanavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Atazanavir; Cobicistat: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with atazanavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of atazanavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor. (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with cobicistat. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of cobicistat, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Atogepant: (Major) Avoid use of atogepant and zanubrutinib when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with zanubrutinib. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and zanubrutinib is a weak CYP3A inducer. Coadministration with a weak CYP3A inducer resulted in a 25% reduction in atogepant overall exposure and a 24% reduction in atogepant peak concentration.
Avanafil: (Major) Coadministration of avanafil with zanubrutinib is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and zanubrutinib is a CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Barbiturates: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Berotralstat: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with berotralstat. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of berotralstat, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; berotralstat is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Bexarotene: (Major) Avoid concurrent use of zanubrutinib and bexarotene due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if bexarotene is discontinued. Zanubrutinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Bosentan: (Major) Avoid concurrent use of zanubrutinib and bosentan due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if bosentan is discontinued. Zanubrutinib is a CYP3A substrate and bosentan is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Butabarbital: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Butalbital; Acetaminophen: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Carbamazepine: (Major) Avoid the concomitant use of zanubrutinib and carbamazepine. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Cenobamate: (Major) Avoid concurrent use of zanubrutinib and cenobamate due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if cenobamate is discontinued. Zanubrutinib is a CYP3A substrate and cenobamate is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Ceritinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ceritinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ceritinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Chloramphenicol: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with chloramphenicol. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of chloramphenicol, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with ciprofloxacin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of ciprofloxacin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Clarithromycin: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with clarithromycin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of clarithromycin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 183% when coadministered with clarithromycin.
Cobicistat: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with cobicistat. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of cobicistat, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Conivaptan: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with conivaptan. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of conivaptan, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A inhibitors.
Crizotinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with crizotinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of crizotinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; crizotinib is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Cyclosporine: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with cyclosporine. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of cyclosporine, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; cyclosporine is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Dabrafenib: (Major) Avoid concurrent use of zanubrutinib and dabrafenib due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if dabrafenib is discontinued. Zanubrutinib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Danazol: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with danazol. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of danazol, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Darunavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with darunavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of darunavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Darunavir; Cobicistat: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with cobicistat. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of cobicistat, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor. (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with darunavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of darunavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with cobicistat. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of cobicistat, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor. (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with darunavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of darunavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Delavirdine: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with delavirdine. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of delavirdine, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Diltiazem: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with diltiazem. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of diltiazem, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; diltiazem is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% when coadministered with diltiazem.
Dronedarone: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with dronedarone. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of dronedarone, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; dronedarone is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Duvelisib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with duvelisib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of duvelisib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Efavirenz: (Major) Avoid concurrent use of zanubrutinib and efavirenz due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if efavirenz is discontinued. Zanubrutinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use with efavirenz is predicted to decrease zanubrutinib exposure by 60%. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of zanubrutinib and efavirenz due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if efavirenz is discontinued. Zanubrutinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use with efavirenz is predicted to decrease zanubrutinib exposure by 60%. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent use of zanubrutinib and efavirenz due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if efavirenz is discontinued. Zanubrutinib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use with efavirenz is predicted to decrease zanubrutinib exposure by 60%. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Elagolix: (Major) Avoid concurrent use of zanubrutinib and elagolix due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if elagolix is discontinued. Zanubrutinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concurrent use of zanubrutinib and elagolix due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if elagolix is discontinued. Zanubrutinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with cobicistat. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of cobicistat, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with cobicistat. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of cobicistat, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Enzalutamide: (Major) Avoid the concomitant use of zanubrutinib and enzalutamide. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Erythromycin: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with erythromycin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of erythromycin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 317% when coadministered with erythromycin.
Eslicarbazepine: (Major) Avoid concurrent use of zanubrutinib and eslicarbazepine due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if eslicarbazepine is discontinued. Zanubrutinib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Etravirine: (Major) Avoid concurrent use of zanubrutinib and etravirine due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if etravirine is discontinued. Zanubrutinib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Fedratinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with fedratinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of fedratinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; fedratinib is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Fluconazole: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with fluconazole. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of fluconazole, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 177% to 284% when coadministered with fluconazole.
Fluvoxamine: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with fluvoxamine. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of fluvoxamine, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; fluvoxamine is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Fosamprenavir: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with fosamprenavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of fosamprenavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A substrate; fosamprenavir is a moderate CYP3A inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A inhibitors.
Fosphenytoin: (Major) Avoid the concomitant use of zanubrutinib and fosphenytoin. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; fosphenytoin is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice or grapefruit-containing foods while taking zanubrutinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Zanubrutinib is a CYP3A4 substrate; grapefruit juice is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Idelalisib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with idelalisib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of idelalisib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Imatinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with imatinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of imatinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; imatinib is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Indinavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with indinavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of indinavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Isavuconazonium: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with isavuconazonium. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of isavuconazonium, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; isavuconazonium is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid the concomitant use of zanubrutinib and rifampin. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with rifampin.
Isoniazid, INH; Rifampin: (Major) Avoid the concomitant use of zanubrutinib and rifampin. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with rifampin.
Itraconazole: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with itraconazole. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of itraconazole, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with itraconazole.
Ketoconazole: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ketoconazole. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ketoconazole, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with clarithromycin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of clarithromycin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 183% when coadministered with clarithromycin.
Lefamulin: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with oral lefamulin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of oral lefamulin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Lenacapavir: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with lenacapavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of lenacapavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A inhibitors.
Letermovir: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with letermovir. Decrease the zanubrutinib dose to 80 mg PO once daily in patients also receiving cyclosporine because the magnitude of the interaction may be increased. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of letermovir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors. The AUC of zanubrutinib was increased by 278% when coadministered with a strong CYP3A4 inhibitor.
Levoketoconazole: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ketoconazole. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ketoconazole, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Lonafarnib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with lonafarnib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of lonafarnib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ritonavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ritonavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Lorlatinib: (Major) Avoid concurrent use of zanubrutinib and lorlatinib due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if lorlatinib is discontinued. Zanubrutinib is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant use of zanubrutinib and lumacaftor; ivacaftor. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Major) Avoid the concomitant use of zanubrutinib and lumacaftor; ivacaftor. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Lumateperone: (Major) Avoid coadministration of lumateperone and zanubrutinib as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; zanubrutinib is a weak CYP3A4 inducer.
Mavacamten: (Major) Avoid concurrent use of zanubrutinib and mavacamten due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if mavacamten is discontinued. Zanubrutinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Methohexital: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Mifepristone: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with mifepristone. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of mifepristone, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Mitotane: (Major) Avoid the concomitant use of zanubrutinib and mitotane. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Nafcillin: (Major) Avoid concurrent use of zanubrutinib and nafcillin due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if nafcillin is discontinued. Zanubrutinib is a CYP3A substrate and nafcillin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with zanubrutinib is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and zanubrutinib is a weak CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with zanubrutinib. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and zanubrutinib is a weak CYP3A inducer.
Nefazodone: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with nefazodone. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of nefazodone, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Nelfinavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with nelfinavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of nelfinavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with netupitant. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of netupitant, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; netupitant is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Nilotinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with nilotinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of nilotinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; nilotinib is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Nirmatrelvir; Ritonavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ritonavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ritonavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of zanubrutinib is necessary. Concomitant use of nirmatrelvir and zanubrutinib may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and zanubrutinib is a weak CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with zanubrutinib as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and zanubrutinib is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concurrent use of zanubrutinib and rifabutin due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if rifabutin is discontinued. Zanubrutinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with rifabutin decreased zanubrutinib exposure by 44%.
Pentobarbital: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Pexidartinib: (Major) Avoid concurrent use of zanubrutinib and pexidartinib due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if pexidartinib is discontinued. Zanubrutinib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Phenobarbital: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Phenytoin: (Major) Avoid the concomitant use of zanubrutinib and phenytoin. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Posaconazole: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with posaconazole. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of posaconazole, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Primidone: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Ribociclib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ribociclib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ribociclib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ribociclib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ribociclib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Rifabutin: (Major) Avoid concurrent use of zanubrutinib and rifabutin due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if rifabutin is discontinued. Zanubrutinib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with rifabutin decreased zanubrutinib exposure by 44%.
Rifampin: (Major) Avoid the concomitant use of zanubrutinib and rifampin. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with rifampin.
Rifapentine: (Major) Avoid the concomitant use of zanubrutinib and rifapentine. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Ritlecitinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with ritlecitinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of ritlecitinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A inhibitors.
Ritonavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ritonavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ritonavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Saquinavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with saquinavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of saquinavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; saquinavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid concurrent use of zanubrutinib and barbiturates due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. Zanubrutinib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer decreased zanubrutinib exposure by 93%.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of zanubrutinib. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and zanubrutinib is a weak CYP3A inducer.
Sotorasib: (Major) Avoid concurrent use of zanubrutinib and sotorasib due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if sotorasib is discontinued. Zanubrutinib is a CYP3A substrate and sotorasib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
St. John's Wort, Hypericum perforatum: (Major) Avoid the concomitant use of zanubrutinib and St. John's Wort. Coadministration may result in decreased zanubrutinib exposure and reduced efficacy. Zanubrutinib is a CYP3A4 substrate; St. John's Wort is a strong CYP3A4 inducer. The AUC of zanubrutinib was decreased by 93% when coadministered with another strong CYP3A4 inducer.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate if coadministration with zanubrutinib is necessary; a tacrolimus dose adjustment may be needed. Concurrent administration may decrease tacrolimus concentrations. Tacrolimus is a sensitive CYP3A substrate with a narrow therapeutic range; zanubrutinib is a weak CYP3A4 inducer.
Tipranavir: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with tipranavir/ritonavir. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of tipranavir/ritonavir, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; tipranavir boosted with ritonavir is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Trandolapril; Verapamil: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with verapamil. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of verapamil, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Tucatinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with tucatinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of tucatinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with zanubrutinib as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; zanubrutinib is a weak CYP3A4 inducer.
Verapamil: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with verapamil. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of verapamil, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; verapamil is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with clarithromycin. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of clarithromycin, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 183% when coadministered with clarithromycin.
Voriconazole: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with voriconazole. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib

therapy as recommended for adverse reactions. After discontinuation of voriconazole, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; voriconazole is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Voxelotor: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with voxelotor. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of voxelotor, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A inhibitors.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with zanubrutinib is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Zanubrutinib is a weak CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.

BRUKINSA Oral Cap: 80mg

Adults

320 mg/day PO.

Geriatric

320 mg/day PO.

Adolescents

Safety and efficacy not established.

Children

Safety and efficacy not established.

Infants

Safety and efficacy not established.

Zanubrutinib is a second generation Bruton tyrosine kinase (BTK) inhibitor. BTK is a signaling molecule early within the B-cell antigen receptor (BCR) signaling cascade. Signaling from BCR regulates several pro-survival mechanisms of B-cells, including proliferation, trafficking, chemotaxis, and adhesion. Zanubrutinib forms a covalent bond with a cysteine residue in the BTK active site leading to inhibition of BTK enzymatic activity, inhibition of malignant B-cell proliferation, and reduced tumor growth.

Zanubrutinib is administered orally. It is approximately 94% protein-bound, with a blood-to-plasma ratio of 0.7 to 0.8. The geometric mean apparent steady-state volume of distribution of zanubrutinib is 537 L (CV, 73%). The median steady-state Bruton's tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells was maintained at 100% over 24 hours at a total daily dose of 320 mg in patients with B-cell malignancies. The median BTK occupancy in lymph nodes was 94% to 100% following the approved recommended dosage. The mean half-life of zanubrutinib is approximately 2 to 4 hours following a single oral dose of 160 mg or 320 mg. The geometric mean apparent oral clearance (CL/F) of zanubrutinib is 128 L/hour (CV, 58%). After a single radiolabeled dose of 320 mg to healthy subjects, approximately 87% was recovered in the feces (38% unchanged), and 8% in urine (less than 1% unchanged).
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A
Zanubrutinib is primarily metabolized by CYP3A; it is also a weak inducer of CYP2C19 and CYP3A. In vitro, zanubrutinib is an inducer of CYP2B6 and CYP2C8, and is likely to be a substrate of P-glycoprotein (P-gp).

Oral Route

After twice-daily dosing of zanubrutinib 160 mg at steady-state, the geometric mean daily AUC is 2,099 ng x hour/mL (CV, 42%) and the geometric mean Cmax is 295 ng/mL (CV, 55%). After once-daily dosing of zanubrutinib 320 mg at steady-state, the geometric mean daily AUC is 1,917 ng x hour/mL (CV, 59%) and the geometric mean Cmax is 537 ng/mL (CV, 55%). The median Tmax of zanubrutinib is 2 hours. Cmax and AUC values of zanubrutinib increase proportionally over a dose range from 40 mg to 320 mg (from 0.13 to 1 time the recommended total daily dose). There was limited systemic accumulation of zanubrutinib following repeated administration.
Effects of food: In healthy subjects, there were no clinically significant differences in the AUC and Cmax values of zanubrutinib after administration of a high-fat meal (approximately 1,000 calories with 50% of total caloric content from fat).

Pregnancy

Zanubrutinib may cause fetal harm if administered during pregnancy based on data from animal studies. Women of reproductive potential should avoid pregnancy during zanubrutinib therapy. Pregnant women should be apprised of the potential hazard to the fetus. In animal studies in pregnant rats, fetal heart malformation and ocular findings (e.g., cataract, protruding eye) were observed following zanubrutinib doses that resulted in drug exposure approximately 5-times of that reported at clinical human doses.

It is not known if zanubrutinib or its metabolites are excreted in human milk or if it has effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions in a nursing child, women should discontinue breast-feeding during zanubrutinib therapy and for 2 weeks after the last dose.