Co-administration of emtricitabine/tenofovir and didanosine is not recommended. Co-administration of tenofovir disoproxil fumarate and didanosine results in a 40-60% increase in systemic exposure to didanosine that may increase the risk for didanosine related adverse reactions. Rarely, pancreatitis and lactic acidosis, sometimes fatal, have been reported. Co-administration of tenofovir disoproxil fumarate and didanosine at a dose of 400 mg daily has been associated with a significant decrease in CD4 cell count, possibly due to an intracellular interaction increasing phosphorylated (i.e. active) didanosine. A decreased dosage of 250 mg didanosine coadministered with tenofovir disoproxil fumarate therapy has been associated with reports of high rates of virological failure within several tested combinations for the treatment of HIV-1 infection. Co-administration with emtricitabine has not been studied.

Coadministration is expected to increase didanosine concentrations. Patients receiving emtricitabine/tenofovir disoproxil and didanosine should be monitored closely for didanosine-associated adverse reactions. Discontinue didanosine in patients who develop didanosine-associated adverse reactions. Higher didanosine concentrations could potentiate didanosine-associated adverse reactions, including pancreatitis, and neuropathy. Suppression of CD4+ cell counts has been observed in patients receiving TDF with didanosine 400 mg daily. In patients weighing greater than 60 kg, reduce the didanosine dose to 250 mg when it is coadministered with emtricitabine/tenofovir disoproxil. Data are not available to recommend a dose adjustment of didanosine for adult or pediatric patients weighing less than 60 kg. When coadministered, Truvada and Videx EC may be taken under fasted conditions or with a light meal (less than 400 kcal, 20% fat). Coadministration of didanosine (250 mg once daily) and tenofovir-DF (300 mg once daily) simultaneously and with a light meal was studied in 33 subjects. When compared to didanosine 400 mg alone under fasting conditions, coadministration of didanosine 250 mg with tenofovir and food decreased didanosine Cmax by 20%, but had no effect on AUC.