Drug Interactions between amoxicillin / clarithromycin / vonoprazan and aripiprazole

ADJUST DOSE: Coadministration with ketoconazole or other potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of aripiprazole, which is partially metabolized by the isoenzyme. According to the product labeling, administration of aripiprazole (15 mg single dose) following pretreatment with ketoconazole (200 mg/day for 14 days) increased the systemic exposure (AUC) to aripiprazole and its active metabolite, dehydro-aripiprazole, by 63% and 77%, respectively, compared to administration of aripiprazole alone. The effect of a higher dosage of ketoconazole has not been studied.

MANAGEMENT: Pharmacologic response to aripiprazole should be monitored more closely whenever ketoconazole or other potent inhibitors of CYP450 3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, nefazodone, cobicistat, delavirdine, protease inhibitors, ketolide and certain macrolide antibiotics) are added to or withdrawn from therapy. The manufacturer recommends that aripiprazole dosage be reduced to one-half the normal dosage during concomitant administration with ketoconazole, and additional dosage adjustments be made based on clinical evaluation. Although clinical data are lacking, similar dosage adjustments may be appropriate during coadministration with other potent CYP450 3A4 inhibitors. Aripiprazole dosage should be increased accordingly if these agents are discontinued.

MONITOR: Coadministration with inhibitors of CYP450 3A4 and/or 2D6 may increase the plasma concentrations of aripiprazole, which is primarily metabolized by these isoenzymes. According to the product labeling, administration of a single 15 mg dose of aripiprazole during treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg/day for 14 days) increased the systemic exposure (AUC) to aripiprazole and its active metabolite, dehydro-aripiprazole, by 63% and 77%, respectively, compared to administration of aripiprazole alone. Likewise, administration of a 10 mg dose of aripiprazole with the potent CYP450 2D6 inhibitor quinidine (166 mg/day for 13 days) increased aripiprazole AUC by 112%, although dehydro-aripiprazole AUC was reduced by 35%.

MANAGEMENT: Pharmacologic response to aripiprazole should be monitored more closely whenever a CYP450 3A4 and/or 2D6 inhibitor is added to or withdrawn from therapy, and the aripiprazole dosage adjusted as necessary. The manufacturer recommends that aripiprazole dosage be reduced to one-half the normal dosage during concomitant administration with ketoconazole or quinidine, and additional dosage adjustments be made based on clinical evaluation. No dosage recommendations are available for concomitant administration with less potent CYP450 2D6 or 3A4 inhibitors.

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.