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 telaprevir. When given with a meal containing 533 kcal and 21 g fat, telaprevir systemic exposure (AUC) increased by 237% compared to administration under fasting conditions. The type of meal also affects the exposure to telaprevir. Relative to fasting, telaprevir AUC increased by approximately 117% with a low-fat meal (249 kcal; 3.6 g fat) and 330% with a high-fat meal (928 kcal; 56 g fat). In Phase 3 clinical trials, telaprevir doses were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat.

MANAGEMENT: Telaprevir should be administered with food containing approximately 20 grams of fat. Patients should be advised that the fat content of the meal or snack is critical to the absorption of telaprevir. Food taken with telaprevir should be ingested within 30 minutes prior to each dose. Examples of some foods that could be taken with telaprevir include: bagel with cream cheese; half cup of nuts; 3 tablespoons of peanut butter; 1 cup of ice cream; 2 ounces of American or cheddar cheese; 2 ounces of potato chips; or half cup of trail mix.