ACALABRUTINIB Drug Interactions: What You Need to Know

INTERACTIONS

• Strong CYP3A Inhibitors : Avoid co-administration with CALQUENCE. ( 2.2 , 7 )
• Moderate CYP3A Inhibitors : Reduce the dosage of CALQUENCE. ( 2.2 , 7 )
• Strong CYP3A Inducers : Avoid co-administration with CALQUENCE. If co-administration is unavoidable, increase the dosage of CALQUENCE. ( 2.2 , 7 )

7.1 Effect of Other Drugs on CALQUENCE Strong CYP3A Inhibitors Clinical Effect Co-administration of CALQUENCE with a strong CYP3A inhibitor increased acalabrutinib plasma concentrations <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Increased acalabrutinib concentrations may result in increased toxicity. Prevention or Management Avoid co-administration of CALQUENCE with strong CYP3A inhibitors. Alternatively, if the inhibitor will be used short-term, interrupt CALQUENCE <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span>. Moderate CYP3A Inhibitors Clinical Effect Co-administration of CALQUENCE with a moderate CYP3A inhibitor may increase acalabrutinib plasma concentration <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Increased acalabrutinib concentrations may result in increased toxicity. Prevention or Management Reduce the dosage of CALQUENCE when co-administered with a moderate CYP3A inhibitor <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span>. Strong CYP3A Inducers Clinical Effect Co-administration of CALQUENCE with a strong CYP3A inducer decreased acalabrutinib plasma concentration <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span> . Decreased acalabrutinib concentrations may reduce CALQUENCE activity. Prevention or Management Avoid co-administration of CALQUENCE with strong CYP3A inducers. If co-administration is unavoidable, increase the dosage of CALQUENCE <span class="opacity-50 text-xs">[see Dosage and Administration (2.2) ]</span>.

None. None. ( 4 )

AND PRECAUTIONS

• Serious and Opportunistic Infections: Monitor for signs and symptoms of infection and treat promptly. ( 5.1 )
• Hemorrhage: Monitor for bleeding and manage appropriately. ( 5.2 )
• Cytopenias: Monitor complete blood counts regularly. ( 5.3 )
• Second Primary Malignancies: Other malignancies have occurred, including skin cancers and other solid tumors. Advise patients to use sun protection. ( 5.4 )
• Cardiac Arrhythmias: Monitor for symptoms of arrhythmias and manage. ( 5.5 )
• Hepatotoxicity, Including Drug Induced Liver Injury: Monitor hepatic function throughout treatment. ( 5.6 )

5.1 Serious and Opportunistic Infections Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE. Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%) <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

5.2 Hemorrhage Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients [ see Adverse Reactions (6.1) ] . Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding. Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

5.3 Cytopenias CALQUENCE can cause Grade 3 or 4 cytopenias.

Grade

3 or 4 cytopenias included absolute neutrophil count decreased (26%), platelets decreased (10%), hemoglobin decreased (10%), and absolute lymphocyte count decreased (10%) in patients treated with CALQUENCE alone or in combination with obinutuzumab; Grade 4 neutropenia developed in 14% [see Adverse Reactions (6.1) ] . Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted [see Dosage and Administration (2.3) ] .

5.4 Second Primary Malignancies Second primary malignancies, including skin cancers and other solid tumors, occurred in 18% of 1,764 patients exposed to CALQUENCE in clinical trials <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . The most frequent second primary malignancy was non-melanoma skin cancer, reported in 10% of patients, followed by other solid tumors in 9% (including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers) and hematologic malignancies (1%). Monitor patients for the development of second cancers and advise protection from sun exposure.

5.5 Cardiac Arrhythmias Serious cardiac arrhythmias have occurred in patients treated with CALQUENCE.

Grade

3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients [see Adverse Reactions (6.1) ] .

Grade

3 or higher ventricular arrhythmia events were reported in 0.9% of patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

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 CALQUENCE. Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE.