Drug Interaction Report

MONITOR: Maraviroc may potentiate the hypotensive effect of some medications. In clinical trials, symptomatic postural hypotension was observed more often with maraviroc than with placebo when administered to healthy volunteers at higher than recommended dosages. However, when given at the recommended dosage to HIV subjects, postural hypotension occurred at a rate similar to placebo (approximately 0.5%).

MANAGEMENT: Caution is advised when maraviroc is prescribed to patients on concomitant medications known to lower blood pressure. Close monitoring for development of hypotension is recommended. Ambulatory patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

Administration with food may reduce the bioavailability of maraviroc. According to the product labeling, coadministration of a 300 mg dose of maraviroc with a high-fat breakfast reduced maraviroc peak plasma concentration (Cmax) and systemic exposure (AUC) by 33% in healthy volunteers. However, no food restrictions were used in the clinical studies that demonstrated the safety and efficacy of maraviroc. Therefore, maraviroc can be taken with or without food at the recommended dosage.