Drug Interactions between Kisqali Femara Co-Pack and upadacitinib

MONITOR CLOSELY: Coadministration of upadacitinib with other immuno- or myelosuppressive agents may potentiate the risk of infections as well as lymphoma 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 upadacitinib, most of whom were taking concomitant immunosuppressants such as methotrexate or corticosteroids. The most common serious infections reported with upadacitinib treatment include pneumonia and cellulitis. Opportunistic infections include tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, and cryptococcosis. Lymphoma and other malignancies have also been observed with upadacitinib use, with or without concomitant immunosuppressants.

MANAGEMENT: Close monitoring for the development of infection is recommended if upadacitinib is used in combination with other immuno- or myelosuppressive agents, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Lymphocyte and neutrophil counts as well as hemoglobin should be evaluated at baseline and regularly during therapy, and upadacitinib dosage adjusted as necessary in accordance with the product labeling. Patients should be advised to contact their physician if they develop signs or symptoms of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, or pain or burning during urination. If a serious or opportunistic infection develops, upadacitinib 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.