Drug Interactions between moxifloxacin / triamcinolone and repotrectinib

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 repotrectinib, a moderate CYP450 3A4 inducer, may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is increased clearance due to induction of CYP450 3A4 activity by repotrectinib. When midazolam, a probe substrate for CYP450 3A4, was administered following treatment with repotrectinib (160 mg once daily for 14 days followed by 160 mg twice daily for 7 days), midazolam systemic exposure (AUC) and peak plasma concentration (Cmax) reduced by 69% and 48%, respectively.

MANAGEMENT: Caution is advised when repotrectinib is used concomitantly with drugs that are substrates of CYP450 3A4. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever repotrectinib is added to or withdrawn from therapy. Avoid concomitant use with repotrectinib where minimal decreases in concentration of the CYP450 3A4 substrate may lead to serious therapeutic failure. If coadministration is required, the CYP450 3A4 substrate dosage should be increased in accordance with approved product labeling.