Drug Interactions between Kisqali Femara Co-Pack and ritlecitinib

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.

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to ribociclib-mediated inhibition of CYP450 3A4 metabolism. In healthy study subjects, administration of midazolam, a sensitive CYP450 3A4 substrate, with multiple 400 mg daily doses of ribociclib increased the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.1-fold and 3.8-fold, respectively, compared to midazolam administered alone. When given at a clinically relevant dose of 600 mg daily, ribociclib is predicted to increase midazolam Cmax and AUC by 2.4-fold and 5.2-fold, respectively.

MANAGEMENT: Caution is advised when ribociclib is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.

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.