Calquence Drug Interactions

Active substances that may increase acalabrutinib plasma concentrations: CYP3A Inhibitors: Co-administration with a strong CYP3A inhibitor (200 mg itraconazole once daily for 5 days) increased acalabrutinib C_max and AUC by 3.7-fold and 5.1-fold in healthy subjects (n=17), respectively.
When accounting for both acalabrutinib and its active metabolite, ACP-5862, physiologically based pharmacokinetic (PBPK) simulations with strong, moderate, and weak CYP3A inhibitors show no meaningful change in total AUC of active components.
Avoid co-administration of strong CYP3A inhibitors with CALQUENCE. Alternatively, if the strong CYP3A inhibitors (e.g., ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, ritonavir, telaprevir, posaconazole, voriconazole) will be used short-term, interrupt CALQUENCE.
Active substances that may decrease acalabrutinib plasma concentrations: CYP3A Inducers: Co-administration of a strong CYP3A inducer (600 mg rifampin once daily for 9 days) decreased acalabrutinib C_max and AUC by 68% and 77% in healthy subjects (n=24), respectively.
When accounting for both acalabrutinib and its active metabolite, ACP-5862, PBPK simulations with strong CYP3A inducers showed a 21-51% decrease in total AUC of active components. Simulations with a moderate CYP3A inducer (efavirenz) showed a 25% decrease in total AUC of active components.
Avoid co-administration of strong inducers of CYP3A activity (e.g., phenytoin, rifampin, carbamazepine) with CALQUENCE. Avoid St. John's wort which may unpredictably decrease acalabrutinib plasma concentrations. If a strong CYP3A inducer cannot be avoided, increase the CALQUENCE dose to 200 mg twice daily.
Gastric Acid Reducing Medications: No clinically significant differences in acalabrutinib pharmacokinetics were observed when a 100 mg acalabrutinib tablet was used concomitantly with rabeprazole (20 mg twice daily for 3 days), a proton pump inhibitor. Acalabrutinib tablets can be co-administered with gastric acid reducing agents (proton pump inhibitors, H2-receptor antagonists, antacids), unlike acalabrutinib capsules which show impaired uptake when given with acid reducing agents.
Active substances whose plasma concentrations may be altered by CALQUENCE: CYP3A Substrates: Based on in vitro data and PBPK modelling, no interaction with CYP substrates is expected at the clinically relevant concentrations (see Pharmacology: Pharmacokinetics under Actions).
Effects of Acalabrutinib and its active metabolite, ACP-5862, on Drug Transport Systems: Acalabrutinib may increase exposure to co-administered BCRP substrates (e.g., methotrexate) by inhibition of intestinal BCRP (see Pharmacology: Pharmacokinetics under Actions).
ACP-5862 may increase exposure to co-administered MATE1 substrates (e.g., metformin) by inhibition of MATE1 (see Pharmacology: Pharmacokinetics under Actions).
Effect of food on acalabrutinib: In healthy subjects, administration of a single 100 mg dose of acalabrutinib with a high fat, high calorie meal (approximately 918 calories, 59 grams carbohydrate, 59 grams fat, and 39 grams protein) did not affect the mean AUC as compared to dosing under fasted conditions. Resulting C_max decreased by 73% and T_max was delayed 1-2 hours.