Drug Interaction Report

MONITOR: Coadministration with ritlecitinib may increase the plasma concentrations and effects of drugs that are primarily metabolized by the CYP450 1A2 isoenzyme. The mechanism is reduced clearance due to inhibition of CYP450 1A2 by ritlecitinib. When ritlecitinib (200 mg once daily for 9 days) was administered in combination with the sensitive CYP450 1A2 substrate caffeine, the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of caffeine increased by 1.10- and 2.65-fold, respectively, compared to administration of caffeine alone. The interaction may be significant for sensitive CYP450 1A2 substrates or those that demonstrate a narrow therapeutic index.

MANAGEMENT: Caution is advised during the concomitant use of ritlecitinib with CYP450 1A2 substrates, particularly sensitive substrates or those that demonstrate a narrow therapeutic index. 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concomitant use is required, clinical and laboratory monitoring may be appropriate whenever ritlecitinib is added to or withdrawn from therapy.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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.