Drug Interaction Report

MONITOR: Coadministration with ritlecitinib may increase the plasma concentrations and effects of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 3A4 by ritlecitinib. When ritlecitinib (200 mg once daily for 11 days) was administered in combination with the sensitive CYP450 3A4 substrate midazolam, the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of midazolam increased by 1.81- and 2.69-fold, compared to administration of midazolam alone. The interaction may be significant for sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index.

MANAGEMENT: Caution is advised with the concomitant use of ritlecitinib with CYP450 3A4 substrates, particularly sensitive substrates or those that demonstrate a narrow therapeutic index (e.g., cisapride, ergot alkaloids, colchicine, fentanyl, macrolide immunosuppressants, midazolam, pimozide, triazolam, vinca alkaloids). If concomitant use is required, clinical and laboratory monitoring may be appropriate whenever ritlecitinib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.