Drug Interaction Report

MONITOR: Because entecavir is primarily eliminated by renal excretion, coadministration with drugs that affect renal function may alter the plasma concentrations of entecavir and/or the coadministered drug. In patients with renal impairment, the apparent oral clearance of entecavir has been shown to decrease as the creatinine clearance decreases. In a small pilot study consisting of nine liver transplant recipients on a stable dose of cyclosporine or tacrolimus, entecavir exposure was approximately 2-fold that in healthy subjects with normal renal function. Altered renal function contributed to the increase in entecavir exposure in these patients.

MANAGEMENT: Caution is advised if entecavir is prescribed in combination 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 should be evaluated prior to and during therapy with entecavir. Dosage adjustment is required in patients with renal insufficiency (creatinine clearance below 50 mL/min) at baseline or during treatment in accordance with the manufacturer's product labeling.

ADJUST DOSING INTERVAL: Food delays the oral absorption and reduces the oral bioavailability of entecavir. According to the product labeling, administration of entecavir 0.5 mg with a standard high-fat meal or a light meal resulted in a delay in absorption by 0.25 to 0.75 hours, a decrease in the peak plasma concentration (Cmax) by 44% to 46%, and a decrease in the area under the plasma concentration-time curve (AUC) by 18% to 20% compared to administration in the fasting state.

MANAGEMENT: To ensure maximal oral absorption, entecavir should be administered on an empty stomach at least 2 hours after a meal and 2 hours before the next meal.