Drug Interactions between abrocitinib and Kisqali Femara Co-Pack

GENERALLY AVOID: Coadministration of abrocitinib with other immunosuppressive agents may potentiate the risk of infections as well as lymphoma, lung cancer and other malignancies. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving Janus kinase inhibitors. Lymphoma and other malignancies, including melanoma and non-melanoma skin cancers, have also been observed with abrocitinib use. Herpes zoster and herpes simplex viral reactivation were also reported during clinical studies with abrocitinib.

MANAGEMENT: Abrocitinib should not be used in combination with other Janus kinase inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or potent immunosuppressants (e.g., azathioprine, cyclosporine). Patients receiving abrocitinib 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 or an opportunistic infection develops, abrocitinib 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.

Coadministration with inhibitors of CYP450 2C19 may increase the plasma concentrations of abrocitinib, which is primarily metabolized by CYP450 2C19 (approximately 53%) and 2C9 (30%) and to a lesser extent by CYP450 3A4 (11%) and 2B6 (6%) based on in vitro data. When a 100 mg dose of abrocitinib was coadministered with fluvoxamine, a potent CYP450 2C19 inhibitor and a weak to moderate CYP450 2C9 and 3A4 inhibitor, or fluconazole, a potent CYP450 2C19 inhibitor and a moderate CYP450 2C9 and 3A inhibitor, the sum systemic exposure (AUC) of unbound abrocitinib plus its two active mono-hydroxylated metabolites, M1 (3-hydroxypropyl) and M2 (2-hydroxypropyl), increased by 91% and 155%, respectively. No data are available for other, less potent CYP450 2C19 inhibitors; however, clinically significant interactions are not expected.