Drug Interactions between aprepitant and atazanavir

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of aprepitant, which is primarily metabolized by the isoenzyme. According to the manufacturer, administration of a single 125 mg dose of aprepitant on day 5 of treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 10 days) resulted in a 5-fold increase in mean aprepitant systemic exposure (AUC) and a 3-fold increase in mean terminal half-life. In patients with mild to moderate hypertension, coadministration of aprepitant (approximately 230 mg once a day) and the moderate inhibitor diltiazem (120 mg three times a day for 5 days) resulted in a 2-fold increase in the AUC of aprepitant and a 1.7-fold increase in that of diltiazem. No clinically significant changes in ECG, heart rate, or blood pressure were observed beyond those induced by diltiazem alone.

MANAGEMENT: Caution is advised if aprepitant is prescribed in combination with CYP450 3A4 inhibitors, particularly potent ones like itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, conivaptan, idelalisib, nefazodone, telithromycin, cobicistat, delavirdine, and protease inhibitors. Pharmacologic response to aprepitant should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. In addition, many CYP450 3A4 inhibitors are also substrates of the isoenzyme, thus pharmacologic response to these agents should also be monitored during coadministration with aprepitant.

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