Drug Interaction Report

CONTRAINDICATED: Coadministration of cidofovir with other nephrotoxic agents may increase the risk of renal impairment due to additive effects on the kidney. Dose-related nephrotoxicity is the major toxicity of cidofovir. Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with as few as one or two doses of cidofovir. Proteinuria may be an early indicator of cidofovir-related nephrotoxicity, and continued treatment may lead to additional proximal tubular cell injury resulting in glycosuria; decreases in serum phosphate, uric acid, and bicarbonate; elevations in serum creatinine; and acute renal failure. Some reported cases have met the criteria of Fanconi syndrome. In clinical trials, cases of nephrotoxicity in which renal function did not return to baseline after drug discontinuation have also been reported.

MANAGEMENT: Concomitant use of cidofovir with other potentially nephrotoxic agents (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; aminosalicylates; antiviral/antiretroviral agents such as acyclovir, adefovir, foscarnet, ganciclovir, and tenofovir; antineoplastics such as aldesleukin, cisplatin, clofarabine, ifosfamide, streptozocin, and high intravenous dosages of methotrexate; chelating agents such as deferasirox, deferoxamine, edetate disodium, and edetate calcium disodium; immunosuppressants such as cyclosporine, everolimus, sirolimus, and tacrolimus; intravascular contrast media; intravenous bisphosphonates; intravenous pentamidine; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents; gallium nitrate; lithium; penicillamine) is considered contraindicated. Such agents should be discontinued for at least seven days prior to starting therapy with cidofovir. Initiation of cidofovir is also contraindicated in patients with a serum creatinine >1.5 mg/dL, a calculated creatinine clearance <=55 mL/min, or a urine protein >=100 mg/dL (2+ proteinuria or greater).

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.