Drug Interactions between aspirin / caffeine / dihydrocodeine and ritlecitinib

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concomitant use is required, clinical and laboratory monitoring may be appropriate whenever ritlecitinib is added to or withdrawn from therapy.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.

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concomitant use is required, clinical and laboratory monitoring may be appropriate whenever ritlecitinib is added to or withdrawn from therapy.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.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.