Drug Interactions between amoxicillin / clarithromycin / vonoprazan and capivasertib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of capivasertib, which is a substrate of the isoenzyme. Based on clinical studies and model-informed approaches, concomitant use with the potent CYP450 3A4 inhibitor itraconazole is predicted to increase capivasertib systemic exposure (AUC) by up to 1.7-fold and peak plasma concentration (Cmax) by up to 1.4-fold. Coadministration with the moderate CYP450 3A4 inhibitors erythromycin and verapamil is predicted to increase the AUC and Cmax of capivasertib by up to 1.5-fold and 1.3-fold, respectively. Increased exposure to capivasertib may increase the risk of adverse effects such as diarrhea, cutaneous adverse reactions, decreased lymphocytes, decreased hemoglobin, hyperglycemia, nausea, and fatigue.

MANAGEMENT: Concomitant use of capivasertib with potent CYP450 3A4 inhibitors should generally be avoided. If concomitant use cannot be avoided, the manufacturer recommends reducing the capivasertib dosage to 320 mg orally twice daily for 4 days followed by 3 days off. Following discontinuation of the potent CYP450 3A4 inhibitor, the capivasertib dosage should be returned (after 3 to 5 half-lives of the inhibitor) to the dosage that was used before starting the inhibitor. Monitoring patients for adverse reactions is also advised.

MONITOR: Coadministration with weak inhibitors of CYP450 3A4 may increase the plasma concentrations of capivasertib, which is a substrate of the isoenzyme. Based on clinical studies and model-informed approaches, concomitant use with the potent CYP450 3A4 inhibitor itraconazole is predicted to increase capivasertib systemic exposure (AUC) by up to 1.7-fold and peak plasma concentration (Cmax) by up to 1.4-fold. Coadministration with the moderate CYP450 3A4 inhibitors erythromycin and verapamil is predicted to increase the AUC and Cmax of capivasertib by up to 1.5-fold 1.3-fold, respectively. Data for other, less potent CYP450 3A4 inhibitors are not available.

MANAGEMENT: Caution and clinical monitoring are recommended if capivasertib is coadministered with weak CYP450 3A4 inhibitors. Patients should be advised to notify their health care professional if they experience increased side effects of capivasertib such as diarrhea, cutaneous adverse reactions, hyperglycemia, nausea, and fatigue.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.