Drug Interactions between dexamethasone / moxifloxacin and eliglustat

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 inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the plasma concentrations of eliglustat, which is primarily metabolized by CYP450 2D6 and, to a lesser extent, CYP450 3A4. Eliglustat is also a substrate of P-gp efflux transporter. In pharmacokinetic studies, treatment with the potent CYP450 3A4/P-gp inducer rifampin (600 mg once daily) decreased eliglustat peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 90% in CYP450 2D6 extensive and intermediate metabolizers administered eliglustat 127 mg twice daily, and 95% in poor metabolizers administered eliglustat 84 mg twice daily. No data are available for use with other, less potent inducers.

MANAGEMENT: Patients receiving eliglustat with CYP450 3A4 inducers should be monitored for potentially diminished pharmacologic response to eliglustat. Concomitant use should be avoided if an interaction is suspected.