Drug Interaction Report

MONITOR: Gadobenate dimeglumine may compete with other substrates of the canalicular multispecific organic anion transporter, also known as cMOAT or MRP2, which is an endogenous transporter protein that works in coordination with the conjugation process to facilitate drug excretion. In solid tumor cells, overexpression of MRP2 confers resistance to a wide variety of anticancer chemotherapeutic agents. Substrates of MRP2 include anthracyclines, protease inhibitors, taxanes, vinca alkaloids, cisplatin, etoposide, methotrexate, and tamoxifen. Theoretically, competition for MRP2 transport may interfere with the clearance of these drugs and/or gadobenate dimeglumine. In patients with tumor cell lines that express MRP2, the interaction may also result in enhanced pharmacologic response to some chemotherapeutic agents.

MANAGEMENT: Caution is advised during concomitant use of gadobenate dimeglumine and other substrates of MRP2. Patients should be monitored for potentially increased pharmacologic effects of gadobenate dimeglumine as well as the coadministered drug(s).

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.