Drug Interactions between amoxicillin / clarithromycin / vonoprazan and sonidegib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of sonidegib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers, administration of a single 800 mg dose of sonidegib five days after starting treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice daily for 14 days) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.5- and 2.2-fold, respectively, compared to administration of sonidegib alone. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that sonidegib steady-state AUC would similarly increase in cancer patients taking sonidegib 200 mg once daily with a potent CYP450 3A4 inhibitor for 14 days.

MANAGEMENT: Concomitant use of sonidegib with potent CYP450 3A4 inhibitors should generally be avoided.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of sonidegib, which is primarily metabolized by the isoenzyme. In 15 healthy volunteers, administration of a single 800 mg dose of sonidegib five days after starting treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice daily for 14 days) increased mean sonidegib peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.5- and 2.2-fold, respectively, compared to administration of sonidegib alone. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that sonidegib steady-state AUC would similarly increase in cancer patients taking sonidegib 200 mg once daily with a potent CYP450 3A4 inhibitor for 14 days. In addition, PBPK simulations predict that sonidegib steady-state AUC would increase approximately 1.8-fold when sonidegib 200 mg once daily is coadministered with the moderate CYP450 3A4 inhibitor erythromycin for 14 days, and 2.8-fold when coadministered with erythromycin for 4 months. No data are available for other, less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is advised when sonidegib is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for potentially increased adverse reactions, particularly musculoskeletal toxicity, and sonidegib treatment interrupted or discontinued accordingly.

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.