Drug Interactions between amoxicillin / clarithromycin / vonoprazan and rifapentine

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with potent CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 80%. Reduced efficacy of vonoprazan may occur.

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

MONITOR: Coadministration with rifapentine may decrease the plasma concentrations of drugs that are substrates of the CYP450 2C8, 2C9, and/or 3A4 isoenzymes. The mechanism is accelerated clearance due to induction of these isoenzymes by rifapentine. Enzyme activities may be induced within 4 days of the first dose and return to normal 14 days after discontinuation of rifapentine. In vitro and in vivo enzyme studies have suggested rifapentine induction potential to be less than that of rifampin but greater than that of rifabutin. In addition, the magnitude of induction is dependent on dose and dosing frequency.

MANAGEMENT: The possibility of a diminished therapeutic response to drugs that are known substrates of CYP450 2C8, 2C9, and/or 3A4 should be considered during coadministration with rifapentine. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs, particularly those with a narrow therapeutic range, whenever rifapentine is added to or withdrawn from therapy.

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.