Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ivermectin and the risk of adverse effects. The proposed mechanism, based on in vitro data, is decreased clearance due to inhibition of CYP450 3A4, the primary isoenzyme responsible for the metabolic clearance of ivermectin.

MANAGEMENT: Caution is advised when ivermectin must be used concomitantly with potent CYP450 3A4 inhibitors. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a potent CYP450 3A4 inhibitor is added to or withdrawn from therapy.

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.