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.

MONITOR: Coadministration with isavuconazonium sulfate (prodrug of isavuconazole) may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 and/or P-glycoprotein (P-gp). The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity and/or P-gp-mediated efflux of these drugs by isavuconazole. In pharmacokinetic studies, isavuconazole increased the systemic exposure (AUC) of sensitive CYP450 3A4 substrates midazolam, sirolimus, and tacrolimus by approximately 2-fold, thus it can be considered a moderate inhibitor of the isoenzyme.

MANAGEMENT: Caution is advised when isavuconazonium sulfate is used concomitantly with drugs that are substrates of the CYP450 3A4 isoenzyme or the P-gp transport protein, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever isavuconazonium sulfate is added to or withdrawn from therapy.