Drug Interactions between moxifloxacin / triamcinolone and telotristat

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 telotristat ethyl may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4 and/or 2B6 isoenzymes. The proposed mechanism is accelerated clearance due to induction of CYP450 3A4 and/or 2B6 (in vitro) isoenzymes by telotristat ethyl. When the probe CYP450 3A4 substrate midazolam (3 mg) was administered orally after 5 days of treatment with telotristat ethyl 500 mg three times daily (twice the recommended dosage), mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 25% and 48%, respectively, compared to administration of midazolam alone. The mean Cmax and AUC of the active metabolite, 1'-hydroxymidazolam, also decreased by 34% and 48%, respectively. This suggests induction by telotristat ethyl of the glucuronidation of 1'-hydroxymidazolam.

MANAGEMENT: When drugs that are known substrates of CYP450 3A4 and/or 2B6 are coadministered with telotristat ethyl, the possibility of a diminished therapeutic response to those drugs should be considered. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs, particularly those with a narrow therapeutic range, whenever telotristat ethyl is added to or withdrawn from therapy.