Drug Interactions between formoterol / mometasone and ritlecitinib

MONITOR: Coadministration with ritlecitinib may increase the plasma concentrations and effects of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 3A4 by ritlecitinib. When ritlecitinib (200 mg once daily for 11 days) was administered in combination with the sensitive CYP450 3A4 substrate midazolam, the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of midazolam increased by 1.81- and 2.69-fold, compared to administration of midazolam alone. The interaction may be significant for sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index.

MANAGEMENT: Caution is advised with the concomitant use of ritlecitinib with CYP450 3A4 substrates, particularly sensitive substrates or those that demonstrate a narrow therapeutic index (e.g., cisapride, ergot alkaloids, colchicine, fentanyl, macrolide immunosuppressants, midazolam, pimozide, triazolam, vinca alkaloids). If concomitant use is required, clinical and laboratory monitoring may be appropriate whenever ritlecitinib is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

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Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.

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