Drug Interactions between amoxicillin / clarithromycin / vonoprazan and tecovirimat

MONITOR: Coadministration with tecovirimat may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. Tecovirimat is a weak inducer of CYP450 3A4. In a drug interaction study involving 24 healthy subjects, a single 2 mg dose of midazolam was coadministered with tecovirimat (600 mg twice daily), and the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 39% and 32%, respectively.

MANAGEMENT: The potential for diminished pharmacologic effects of CYP450 3A4 substrates should be considered during coadministration with tecovirimat.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with potent and moderate CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 80% and 50%, respectively. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of vonoprazan should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

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.