Boceprevir + Pravastatin = Precautionary

Effect on Concentration

Boceprevir
No change
Applies within class?
No
Pravastatin
Increase
Applies within class?
No

Pharmacologic Effects

Boceprevir
Effect
N/A
Applies within class?
No
Pravastatin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 10-Jul-2018

Summary

This interaction could be due to the inhibitory effect of boceprevir on OATP, while pravastatin is a substrate. Because of the increased risk for myopathy and rhabdomyolysis the manufacturer has issued prescribing recommendations. The manufacturer of boceprevir recommends that when co-administering with pravastatin to use close clinical monitoring. An alternative HMG-CoA reductase inhibitor such as low dose rosuvastatin or pitavastatin could be considered if combined use with a protease inhibitor is necessary. However, always use the lowest possible dose of the HMG-CoA reductase inhibitor and monitor patients closely for any signs or symptoms of toxicity.

Sources

Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin. ^

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.