Drug Interactions between dexamethasone / moxifloxacin and istradefylline

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.

MONITOR: Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of istradefylline, which is primarily metabolized by CYP450 3A4 and 1A1. In study subjects, administration of istradefylline with the potent CYP450 3A4 inducer rifampin (600 mg daily for 20 days) led to a reduction in the peak plasma concentration (Cmax) and total systemic exposure (AUC(inf)) of istradefylline by 45% and 81%, respectively, when compared with istradefylline administered alone. No data are available regarding the effects that other, less potent CYP450 3A4 inducers will have on the pharmacokinetics of istradefylline.

MANAGEMENT: Caution is advised if istradefylline is used with moderate CYP450 3A4 inducers. Clinical monitoring of istradefylline should be considered whenever a moderate CYP450 3A4 inducer is added to or withdrawn from therapy. Patients should be monitored for diminished therapeutic effects.