Drug Interactions between amoxicillin / clarithromycin / vonoprazan and sotorasib

MONITOR: Coadministration with sotorasib may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is increased metabolic clearance due to induction of CYP450 3A4 by sotorasib. When midazolam, a sensitive CYP450 3A4 substrate, was coadministered with sotorasib, midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 48% and 53%, respectively. These results suggest moderate induction of CYP450 3A4 by sotorasib.

MANAGEMENT: Caution is advised when sotorasib is used concomitantly with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. The prescribing information recommends avoiding coadministration of sotorasib with CYP450 3A4 substrates for which minimal concentration changes may lead to therapeutic failure. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever sotorasib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of a moderate CYP450 3A4 inducer like sotorasib and for any dosage adjustments that may be required.

GENERALLY AVOID: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with moderate CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 50%. Reduced efficacy of vonoprazan may occur.

MANAGEMENT: According to the manufacturer, concomitant use of vonoprazan with moderate CYP450 3A4 inducers should be avoided.

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.