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: Food delays but enhances the oral absorption and bioavailability of ganciclovir capsules, possibly due to prolongation of gastrointestinal transit time. In 20 HIV- and CMV-seropositive subjects, ganciclovir dosing (1000 mg every 8 hours) following a standardized high-fat breakfast increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ganciclovir by an average of 15% and 22%, respectively, compared to dosing after an overnight fast. The time to reach peak plasma concentration (Tmax) was prolonged from 1.8 to 3 hours. In another study of 15 such patients, administration of ganciclovir (2000 mg) within 30 minutes following a high-fat breakfast increased the Cmax and AUC an average of 111% and 114%, respectively, compared to administration in the fasting state (i.e. at least 1 hour before or 2 hours after a meal or snack). Over the total day of dosing (2000 mg orally three times a day), there was a mean increase of 48% and 97% in Cmax and AUC, respectively, and a 36% decrease in half-life during administration with meals.

MANAGEMENT: To ensure maximal oral absorption, oral ganciclovir should be administered with or immediately after a meal.

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.