Drug Interaction Report

MONITOR: Coadministration of a macrolide or ketolide antibiotic (clarithromycin, erythromycin, telithromycin) with a hepatitis C virus (HCV) NS3/4A protease inhibitor (boceprevir, telaprevir) is expected to increase the plasma concentrations of both drugs. The mechanism may involve both competitive and noncompetitive inhibition of CYP450 3A4, since these drugs are all substrates as well as inhibitors of the isoenzyme. No pharmacokinetic data are currently available. Clinically, high plasma levels of macrolide or ketolide antibiotics may increase the risk of QT interval prolongation and torsade de pointes arrhythmia.

MANAGEMENT: Caution and close clinical monitoring are recommended if clarithromycin, erythromycin, or telithromycin are used in combination with a HCV NS3/4A protease inhibitor. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.