There was no clinically meaningful impact of boceprevir on methadone or buprenorphine pharmacokinetics, suggesting that methadone/buprenorphine dose adjustments are not required upon coadministration with boceprevir. Individual patients may differ in their clinical experience and clinicians should maintain vigilance when coadministering these medications.

bBoceprevir is a potent orally administered inhibitor of hepatitis C virus and a strong, reversible inhibitor of CYP3A4, the primary metabolic pathway for many 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Thus, the aim of the present study was to investigate drug-drug interactions between atorvastatin or pravastatin and boceprevir. We conducted a single-center, open-label, fixed-sequence, one-way-crossover study with 20 healthy adult volunteers. Subjects received single-dose atorvastatin (40 mg) or pravastatin (40 mg) on day 1, followed by boceprevir (800 mg three times daily) for 7 to 10 days. Repeat single doses of atorvastatin or pravastatin were administered in the presence of steady-state boceprevir. Atorvastatin exposure increased in the presence of boceprevir, with atorvastatin area under the concentrationtime curve from time zero to infinity after single dosing (AUC inf ) increasing 2.3-fold (90% confidence interval [CI], 1.85, 2.90) and maximum observed concentration in plasma (C max ) 2.7-fold (90% CI, 1.81, 3.90). Pravastatin exposure was slightly increased in the presence of boceprevir, with pravastatin AUC inf increasing 1.63-fold (90% CI, 1.03, 2.58) and C max 1.49-fold (90% CI, 1.03, 2.14). Boceprevir exposure was generally unchanged when the drug was coadministered with atorvastatin or pravastatin. All adverse events were mild and consistent with the known safety profile of boceprevir. The observed 130% increase in AUC of atorvastatin supports the use of the lowest possible effective dose of atorvastatin when coadministered with boceprevir, without exceeding a maximum daily dose of 40 mg. The observed 60% increase in pravastatin AUC with boceprevir coadministration supports the initiation of pravastatin treatment at the recommended dose when coadministered with boceprevir, with close clinical monitoring. W orldwide, there are an estimated 130 to 170 million individuals infected with hepatitis C virus (1). Comorbidities, such as diabetes and obesity, are more common among patients with hepatitis C virus infection than in the general U.S. population, with as many as 25% of patients with hepatitis C virus infection at risk of comorbid disorders of lipid metabolism (2). Thus, patients with hepatitis C virus infection frequently receive concomitant treatments for hyperlipidemia, including the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors atorvastatin and pravastatin. Understanding potential drug interactions between hepatitis C therapies and HMG-CoA reductase inhibitors is important for optimal treatment of this patient population.Boceprevir is a potent, orally administered ketoamide inhibitor targeting the active site of the hepatitis C virus nonstructural protein 3 (NS3) protease, approved for the treatment of genotype 1 chronic hepatitis C virus infection in adult patients with compensated liver disease (3-6). Addition of boceprevir to a pegylated interferon (peginterferon)-ribavirin backbone is associated with significantly increased rates of sustain...