Drug Interaction Report

MONITOR: Drugs that impair glomerular filtration may prolong the half-life of flucytosine and lead to accumulation. Prolonged flucytosine serum concentrations of greater than 100 mcg/mL may increase the risk of gastrointestinal, hepatic, and hematologic toxicity.

MANAGEMENT: Caution is advised if flucytosine is used in patients who have recently received or are receiving treatment with potentially nephrotoxic drugs (e.g., aminoglycosides; polypeptide, glycopeptide, and polymyxin antibiotics; amphotericin B; adefovir; cidofovir; tenofovir; foscarnet; cisplatin; deferasirox; gallium nitrate; lithium; mesalamine; certain immunosuppressants; intravenous bisphosphonates; intravenous pentamidine; high intravenous dosages of methotrexate; high dosages and/or chronic use of nonsteroidal anti-inflammatory agents). Renal function and flucytosine blood levels should be closely monitored during therapy, and the dose or dosing interval should be adjusted to maintain flucytosine concentrations below 100 mcg/mL.

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.