Drug Interaction Report

MONITOR CLOSELY: Coadministration of baricitinib 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 baricitinib, most of whom were taking concomitant immunosuppressants such as methotrexate or corticosteroids. The most common serious infections reported with baricitinib treatment include pneumonia, herpes zoster, and urinary tract infection. Opportunistic infections include tuberculosis, multidermatomal herpes zoster, esophageal candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis, cytomegalovirus, and BK virus. Lymphoma and other malignancies have also been observed with baricitinib use, with or without concomitant immunosuppressants.

MANAGEMENT: Close monitoring for the development of infection is recommended if baricitinib 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 baricitinib dosage adjusted as necessary in accordance with the product labeling. Patients should be advised to contact their physician if they develop signs and 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, and pain or burning during urination. If a serious infection, an opportunistic infection, or sepsis develops, baricitinib should be interrupted until the infection is controlled.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of umbralisib. When a single oral dose of umbralisib was administered with a high-fat, high-calorie meal (approximately 917 calories; 171 calories from protein, 232 calories from carbohydrate, 502 calories from fat) in healthy subjects, umbralisib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 115% and 61%, respectively, compared to administration under fasted conditions.

MANAGEMENT: Umbralisib should be administered with food at approximately the same time each day.