Drug Interactions between amoxicillin / clarithromycin / vonoprazan and nevirapine

GENERALLY AVOID: Coadministration with nevirapine may significantly decrease the plasma concentrations of clarithromycin. The mechanism is nevirapine induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of clarithromycin. In 15 HIV-positive subjects, nevirapine (200 mg once daily for 2 weeks followed by 200 mg twice daily for 2 weeks) decreased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of clarithromycin (500 mg twice a day) by 23%, 31% and 57%, respectively, compared to administration of clarithromycin alone. In contrast, the Cmax and AUC of its 14-hydroxy metabolite increased by 47% and 42%, respectively, while the Cmin remained unchanged. Although 14-hydroxy-clarithromycin is pharmacologically active, it has reduced activity against Mycobacterium avium-intracellulare complex, thus overall activity against this pathogen may be compromised.

MANAGEMENT: Clarithromycin should preferably not be used in the treatment and prophylaxis of Mycobacterium avium-intracellulare complex in patients treated with nevirapine. Alternatives such as azithromycin should be considered.

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.