Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin.
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Study Design
A drug-drug interaction study examined the effect of boceprevir on the AUC and Cmax of atorvastatin and the effect of atorvastatin on the PK of boceprevir. Ten healthy men and women were given 40mg of atorvastatin on day 1, 800mg of boceprevir TID days 4-10, and 40mg of atorvastatin on day 9.
Study Results
Boceprevir had a large impact on atorvastatin, the geometric mean for AUCinf and Cmax increased by 2.30- and 2.66-fold, respectively. While atorvastatin had minimal effect on boceprevir, change in mean Cmax was 1.04 (0.89-1.21) and the change in mean AUC was 0.95 (0.90 - 1.01).
Study Conclusions
This interaction could be due to the inhibitory effect of boceprevir on CYP3A4 and OATP1B1, while atorvatstain is a substrate of these metabolic and transport pathways. Because of the increased risk for myopathy and rhabdomyolysis from the combination of certain protease inhibitors and atorvastatin the manufacturer has issued prescribing recommendations. The manufacturer of boceprevir recommend that when co-administering with atorvastatin to use the lowest effective dose of atorvastatin, but to not exceed 40mg daily of atorvastatin. It is recommended to monitor the patient closely for adverse effects and to use caution.
References
Hulskotte, E. G., Feng HP, Xuan F, Gupta S, van Zutven MGJA, Omara E, Butterton JR. Pharmacokinetic evaluation of the interaction between hepatitis c virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors atorvastatin and pravastatin. Antimicrobial Agents And Chemotherapy . 2013; 6: 2582-2588.
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