Drug Interaction Report

MONITOR: Coadministration of tenofovir with other drugs that are also eliminated by active tubular secretion may result in increased plasma concentrations of tenofovir and/or the coadministered drug(s) due to competition for renal excretion. Drugs that are thought to undergo active tubular secretion include acyclovir, amiloride, cidofovir, cimetidine, flecainide, ganciclovir, metformin, midodrine, procainamide, quinidine, ranitidine, triamterene, valacyclovir, and valganciclovir.

MANAGEMENT: Patients receiving tenofovir in combination with other drugs that undergo active tubular secretion should be monitored for excessive pharmacologic effects of all drugs, and the dosages adjusted as necessary. Because tenofovir is associated with dose-related nephrotoxicity, especially proximal renal tubulopathy, renal function tests including serum creatinine, serum phosphorous, estimated creatinine clearance, urine glucose, and urine protein should be performed prior to and during therapy. Patients with renal insufficiency at baseline or during treatment may require dosage adjustment in accordance with the manufacturer's product labeling. Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may also be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.