Drug Interactions between alvimopan and naldemedine

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of naldemedine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In pharmacokinetic studies, naldemedine systemic exposure (AUC) was increased approximately 90% by the moderate CYP450 3A4 inhibitor fluconazole and nearly 200% by the potent inhibitor itraconazole. The interaction has not been studied with grapefruit juice. 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. Increased exposure to naldemedine may precipitate opioid withdrawal symptoms such as hyperhidrosis, lacrimation, rhinorrhea, chills, diarrhea, abdominal pain, anxiety, insomnia, irritability, restlessness, and yawning.

Food does not significantly affect the overall bioavailability of naldemedine. When administered with a high-fat meal, the rate of naldemedine absorption was decreased, but not the extent. Specifically, naldemedine peak plasma concentration (Cmax) was decreased by approximately 35% and time to achieve Cmax was delayed from 0.75 hours in the fasted state to 2.5 hours in the fed state, while naldemedine AUC was not significantly changed.

MANAGEMENT: Naldemedine may be taken with or without food. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with naldemedine.

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Coadministration with a high-fat meal may decrease the rate and extent of alvimopan absorption. According to the product labeling, alvimopan peak plasma concentration (Cmax) and systemic exposure (AUC) were decreased by approximately 38% and 21%, respectively, and the time to reach peak plasma concentration (Tmax) was prolonged by approximately 1 hour when taken with a high-fat meal. The clinical significance is unknown. In postoperative ileus clinical trials, the preoperative dose of alvimopan was administered in a fasting state, and subsequent doses were given without regard to meals.

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

• alvimopan
• naldemedine

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.