Drug Interaction Report

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with the hepatitis C virus (HCV) NS3/4A protease inhibitors, boceprevir and telaprevir, may decrease the plasma concentrations and efficacy of hormonal contraceptives. The mechanism involves induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. When an oral contraceptive containing drospirenone-ethinyl estradiol (3 mg-0.02 mg daily for 14 days) was given in combination with boceprevir (800 mg three times daily for 7 days), ethinyl estradiol systemic exposure (AUC) decreased by approximately 25%, with no change in the peak plasma concentration (Cmax). In a study of 24 subjects who were administered an oral contraceptive containing ethinyl estradiol-norethindrone (0.035 mg-0.5 mg daily) concomitantly with telaprevir (750 mg every 8 hours) for 21 days, the Cmax and AUC of ethinyl estradiol decreased by 26% and 28%, respectively. In addition, there was a 33% reduction in the trough plasma concentration (Cmin) of ethinyl estradiol. Norethindrone Cmax, AUC and Cmin decreased by 15%, 11% and 6% during coadministration with telaprevir.

MANAGEMENT: Systemic hormonal contraceptives may be continued, but may not be as effective, during and for up to two weeks following treatment with boceprevir or telaprevir. Because HCV NS3/4A protease inhibitors must be used in combination with peginterferon alfa and ribavirin, and use of ribavirin has been associated with significant birth defects and fetal death, it is particularly important that patients not become pregnant during treatment. Therefore, systemic hormonal contraceptives should not be relied upon as an effective method of birth control in women of childbearing potential treated with HCV NS3/4A protease inhibitors. Two alternative, effective methods of contraception, which may include intrauterine devices and barrier methods, should be used during HCV NS3/4A protease inhibitor treatment in combination with peginterferon alfa and ribavirin. Intrauterine systems are unlikely to be significantly affected because of their local action. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed. Two weeks after completion of HCV NS3/4A protease inhibitor treatment, hormonal contraceptives are again appropriate as one of the two required effective methods of birth control for patients receiving peginterferon alfa and ribavirin.

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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.

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