Drug Interaction Report

The coadministration of ganciclovir or its prodrug, valganciclovir, with trimethoprim may result in elevated plasma concentrations of ganciclovir. In 12 subjects with HIV and CMV coinfection, trimethoprim (200 mg orally once a day) increased the half-life of ganciclovir (1000 mg orally every 8 hours) by an average of 15% and decreased its renal clearance by 16%. The mechanism is unknown but may involve the competitive inhibition of ganciclovir renal tubular secretion by trimethoprim. Ganciclovir had minimal effect on the pharmacokinetics of trimethoprim. This interaction is unlikely to be of clinical significance. . However, the use of ganciclovir with other potentially myelotoxic drugs such as trimethoprim may increase the risk and severity of these adverse events due to additive pharmacodynamic effects. The potential for this effect should be kept in consideration and the patient monitored for hematologic adverse effects.

ADJUST DOSING INTERVAL: Food increases the bioavailability of ganciclovir from the prodrug, valganciclovir. In 16 HIV-positive subjects, the administration of valganciclovir 875 mg once daily with a high-fat meal containing approximately 600 calories resulted in a 30% increase in the steady-state area under the plasma concentration-time curve (AUC) and a 14% increase in the peak plasma concentration (Cmax) of ganciclovir, with no delay in the time to reach peak plasma concentration (Tmax). The mechanism is unknown.

MANAGEMENT: The manufacturer recommends that valganciclovir be taken with meals.