Drug Interaction Report

GENERALLY AVOID: Coadministration of ritlecitinib with other immunosuppressive agents may potentiate the risk of infections as well as malignancies, including non-melanoma skin cancer (NMSC). Serious infections have been reported in patients who have received ritlecitinib. The most common serious infections reported with ritlecitinib included appendicitis, pneumonia, COVID-19, and sepsis. Herpes virus reactivation (e.g., herpes zoster) was also reported during clinical studies with ritlecitinib, as well as malignancies including NMSC.

MANAGEMENT: The safety and efficacy of ritlecitinib in combination with immunosuppressive agents has not been evaluated. It is recommended that the concomitant use of ritlecitinib with other Janus Kinase (JAK) inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants be avoided. Some authorities recommend avoiding ritlecitinib with all systemic immunosuppressive agents. Patients receiving ritlecitinib should be closely monitored for the development of signs and symptoms of infection during and after treatment, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. If a serious infection develops, ritlecitinib therapy should be interrupted until the infection is controlled.

GENERALLY AVOID: Coadministration of protein-bound sirolimus intravenous suspension with grapefruit juice may increase the systemic exposure to sirolimus. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of sirolimus by certain compounds present in grapefruit. However, grapefruit juice primarily inhibits CYP450 3A4-mediated first-pass metabolism in the gut wall and may have limited effects on medications that are not administered orally. No formal studies evaluating the drug interaction potential of protein-bound sirolimus have been conducted. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: The manufacturer recommends avoiding grapefruit and grapefruit juice during treatment with protein-bound sirolimus.