Drug Interaction Report

MONITOR: Theoretically, coadministration with CYP450 3A4 inhibitors may increase the plasma concentrations of topical tacrolimus. The proposed mechanism involves inhibition of CYP450 3A4-mediated metabolism of tacrolimus, which is primary metabolized by this isoenzyme. However, systemic exposure from topical tacrolimus is reported to be minimal (less than 1 ng/mL) and so clinically significant drug interactions are not expected. Nevertheless, the possibility of an interaction cannot be ruled out.

MANAGEMENT: According to the manufacturer, caution is advised if topical tacrolimus is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for systemic tacrolimus adverse effects including immunosuppression, infection, hyperkalemia, malignancy, nephrotoxicity, neurotoxicity, and hypertension.

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.