Drug Interaction Report

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

ADJUST DOSE: Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of crinecerfont, which is primarily metabolized by the isoenzyme. Concomitant use with rifampin, a potent CYP450 3A4 inducer, decreased crinecerfont peak plasma concentration (Cmax) and systemic exposure (AUC) by 23% and 62%, respectively. No data are available for other, less potent inducers. Reduced efficacy of crinecerfont may occur.

MANAGEMENT: When coadministered with moderate CYP450 3A4 inducers, the crinecerfont evening dose should be increased.
In adults, increase the crinecerfont dose to 200 mg with a meal in the evening (morning dose of 100 mg with a meal remains unchanged).

In pediatric patients 4 years of age and older, increase the crinecerfont dose based on weight:
-Patients weighing 10 kg to less than 20 kg: 50 mg with a meal in the evening (morning dose of 25 mg with a meal remains unchanged)
-Patients weighing 20 kg to less than 55 kg: 100 mg with a meal in the evening (morning dose of 50 mg with a meal remains unchanged)
-Patients weighing 55 kg or more: 200 mg with a meal in the evening (morning dose of 100 mg with a meal remains unchanged)

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of crinecerfont. Administration of crinecerfont capsules and oral solution with a high-fat meal (800 to 1000 calories, 50% fat), increased crinecerfont peak plasma concentration (Cmax) by 4.9-fold and 8.6-fold, respectively, and systemic exposure (AUC) by 3.3-fold and 8.3-fold, respectively, compared to administration under fasting conditions.

MANAGEMENT: Crinecerfont should be administered twice daily with a meal in the morning and evening without regard to fat or calorie content.