Drug Interactions between naloxegol and rifapentine

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of naloxegol. 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, naloxegol systemic exposure (AUC) was increased approximately 3.5-fold by the moderate CYP450 3A4 inhibitor diltiazem and nearly 13-fold by the potent inhibitor ketoconazole. 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 naloxegol may precipitate opioid withdrawal symptoms such as hyperhidrosis, lacrimation, rhinorrhea, chills, diarrhea, abdominal pain, anxiety, insomnia, irritability, restlessness, and yawning.

ADJUST DOSING INTERVAL: Food may increase the rate and extent of naloxegol absorption. When administered with a high-fat meal, naloxegol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 30% and 45%, respectively. In clinical trials, naloxegol was given on an empty stomach approximately 1 hour prior to the first meal in the morning.

MANAGEMENT: Patients treated with naloxegol should avoid consumption of grapefruit and grapefruit juice. Naloxegol should be taken on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal.

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ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.

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