Drug Interaction Report

Coadministration with nelfinavir may increase the plasma concentrations of amprenavir. The mechanism is nelfinavir inhibition of amprenavir metabolism via CYP450 3A4. In 6 study subjects, coadministration of nelfinavir (750 mg three times a day) and amprenavir (750 or 800 mg three times a day) for 2 weeks resulted in a 14% decrease in amprenavir peak plasma concentration (Cmax) but a 189% increase in its trough plasma concentration (Cmin) compared to administration of amprenavir alone. Overall systemic exposure (AUC) was unchanged. The clinical significance of these findings is unknown. Patients receiving amprenavir or fosamprenavir with nelfinavir should be monitored for potentially increased side effects of both drugs. Appropriate dosages of the drugs in combination with respect to safety and efficacy have not been established.

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.

The recommended maximum number of medicines in the 'protease inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'protease inhibitors' category:

• Agenerase (amprenavir)
• nelfinavir

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.