Drug Interaction Report

MONITOR: The coadministration of didanosine and ganciclovir may result in significantly elevated plasma concentrations of didanosine, while the pharmacokinetics of ganciclovir are minimally affected. In a study consisting of 11 subjects with HIV infection, ganciclovir (1 gram orally every 8 hours) increased the peak plasma concentration and area under the concentration-time curve of didanosine (200 mg orally every 12 hours) by an average of 58% and 71%, respectively. Other studies have reported similar or even greater alterations with both intravenous and oral ganciclovir. The mechanism is unknown but may involve competitive inhibition of didanosine renal tubular secretion or increased bioavailability of didanosine by ganciclovir. Caution is advised if didanosine must be used concomitantly with ganciclovir or its prodrug, valganciclovir.

MANAGEMENT: Close monitoring for toxicities associated with didanosine such as pancreatitis, lactic acidosis, and peripheral neuropathy is recommended during concurrent therapy. Patients should be advised to promptly notify their physician if they experience possible symptoms of toxicity (e.g., abdominal pain, nausea, vomiting, diarrhea, weakness, dizziness, lightheadedness, irregular heartbeat, or numbness, pain, or tingling in the hands and feet).

ADJUST DOSING INTERVAL: Didanosine bioavailability is decreased when administered with food. Loss of efficacy may result.

MANAGEMENT: Didanosine should be administered in the fasting state, at least 30 minutes before or more than 2 hours after eating.

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.