ZANUBRUTINIB Drug Interactions: What You Need to Know

INTERACTIONS CYP3A Inhibitors: Modify BRUKINSA dose with moderate or strong CYP3A inhibitors as described. ( 2.3 , 7.1 ) CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers. ( 2.3 , 7.1 )

7.1 Effect of Other Drugs on BRUKINSA Table 17: Drug Interactions that Affect Zanubrutinib Moderate and Strong CYP3A Inhibitors Clinical Impact Coadministration with a moderate or strong CYP3A inhibitor increases zanubrutinib C max and AUC <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> which may increase the risk of BRUKINSA toxicities. Prevention or management Reduce BRUKINSA dosage when coadministered with moderate or strong CYP3A inhibitors <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> . Moderate and Strong CYP3A Inducers Clinical Impact Coadministration with a moderate or strong CYP3A inducer decreases zanubrutinib C max and AUC <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> which may reduce BRUKINSA efficacy. Prevention or management Avoid coadministration of BRUKINSA with strong CYP3A inducers <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> . Avoid coadministration of BRUKINSA with moderate CYP3A inducers <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> . If these inducers cannot be avoided, increase BRUKINSA dosage to 320 mg twice daily <span class="opacity-50 text-xs">[see Dosage and Administration (2.3) ]</span> .

None. None. ( 4 )

AND PRECAUTIONS Hemorrhage : Monitor for bleeding and manage appropriately. ( 5.1 ) Infections : Monitor patients for signs and symptoms of infection, including opportunistic infections, and treat as needed. ( 5.2 ) Cytopenias : Monitor complete blood counts during treatment. ( 5.3 )

Second Primary

Malignancies : Other malignancies have developed including skin cancers and non-skin carcinomas. Monitor and advise patients to use sun protection. ( 5.4 )

Cardiac

Arrhythmias : Monitor for signs and symptoms of arrhythmias and manage appropriately. ( 5.5 ) Hepatotoxicity, Including Drug-Induced Liver Injury : Monitor hepatic function throughout treatment. ( 5.6 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise women of the potential risk to a fetus and to use effective contraception. ( 5.7 )

5.1 Hemorrhage Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA.

Grade

3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients. Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage. Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

5.2 Infections Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA.

Grade

3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred. Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

5.3 Cytopenias Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%), and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>.

Grade

4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients. Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted [see Dosage and Administration (2.4) ] . Treat using growth factor or transfusions, as needed.

5.4 Second Primary Malignancies Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

5.5 Cardiac Arrhythmias Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% of patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk.

Grade

3 or higher ventricular arrhythmias were reported in 0.3% of patients. Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately [see Dosage and Administration (2.4) ] , and consider the risks and benefits of continued BRUKINSA treatment.

5.6 Hepatotoxicity, Including Drug-Induced Liver Injury Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA. Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.

5.7 Embryo-Fetal Toxicity Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1) ]</span> .