Drug Interactions between amoxicillin / clarithromycin / vonoprazan and oxcarbazepine

MONITOR: Coadministration with oxcarbazepine may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is accelerated clearance due to induction of CYP450 3A4 activity by oxcarbazepine. In one study, administration of a single 600 mg dose of oxcarbazepine to eight healthy male volunteers had no effect on the pharmacokinetics of the CYP450 3A4 substrate felodipine (10 mg once daily), while repeated doses (450 mg twice a day) reduced the felodipine peak plasma concentration (Cmax) and systemic exposure (AUC) by 34% and 28%, respectively. Likewise, in a case study of a kidney transplant patient receiving cyclosporine 270 mg/day, investigators reported that cyclosporine trough concentrations declined to subtherapeutic levels approximately two weeks after the addition of oxcarbazepine. Trough concentrations returned to therapeutic range following an increase of the cyclosporine dosage to 290 mg/day and a reduction of the oxcarbazepine dosage from 750 mg/day to 600 mg/day. These results indicate that enzymatic induction occurs after multiple doses of oxcarbazepine.

MANAGEMENT: Caution is advised if oxcarbazepine must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever oxcarbazepine is added to or withdrawn from therapy. When initiating treatment or changing the dosage, it may take 2 to 3 weeks to reach the corresponding level of induction. Similarly, the induction is expected to gradually decrease over 2 to 3 weeks following discontinuation of oxcarbazepine.

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.