Drug Interactions between abiraterone and naloxegol

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.

ADJUST DOSING INTERVAL: Food may significantly increase the oral bioavailability of some formulations of abiraterone acetate. Compared to administration in the fasted state, abiraterone peak plasma concentration (Cmax) and systemic exposure (AUC) were approximately 7- and 5-fold higher, respectively, when a single dose of abiraterone acetate was administered with a low-fat meal (7% fat; 300 calories) and approximately 17- and 10-fold higher, respectively, when it was administered with a high-fat meal (57% fat; 825 calories). Given the normal variation in the content and composition of meals, taking abiraterone acetate with meals has the potential to result in increased and highly variable exposures. The safety of these increased exposures during multiple dosing has not been assessed. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, was found to have an approximately 6.5-fold higher Cmax and 4.4-fold higher AUC when a single dose of 500 mg (4 tablets) was administered with a high-fat meal (56% - 60% fat, 900 - 1000 calories) compared to overnight fasting in healthy volunteers. These differences were not considered clinically significant for this formulation.

MANAGEMENT: Some formulations of abiraterone acetate must be taken on an empty stomach. No food should be consumed for at least two hours before and one hour after the abiraterone acetate dose. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, can be taken with or without food. The manufacturer's product labeling should be consulted for specific guidance.