Drug–drug interactions that interfere with statin metabolism

Abstract

Introduction: Lipid-lowering drugs, especially hydroxymethylglutaryl-CoA reductase inhibitors (statins), are widely used in the treatment and prevention of atherosclerotic diseases. The benefits of statins are well documented. However, myotoxic side effects, which can sometimes be severe, including myopathy or rhabdomyolysis, have been associated with the use of statins. In some cases, this toxicity is associated with pharmacokinetic alterations. Potent inhibitors of CYP 3A4 significantly increase plasma concentrations of the active forms of simvastatin, lovastatin and atorvastatin. Fluvastatin is metabolized by CYP2C9, while pravastatin, rosuvastatin and pitavastatin are not susceptible to inhibition by any CYP.

Areas covered: This review discusses the pharmacokinetic aspects of the drug–drug interaction with statins and genetic polymorphisms in CYPs, which are involved in the metabolism of statins, and highlights the importance of establishing a system utilizing electronic medical information practically to avoid adverse drug reactions.

Expert opinion: An understanding of the mechanisms underlying statin interactions will help to minimize drug interactions and develop statins that are less prone to adverse interactions. Quantitatively analyzed information for the low-density lipoprotein cholesterol lowering effects of statin based on electronic medical records may be useful for avoiding the adverse effect of statins.

Keywords:

• atorvastatin
• CYP2C9
• CYP3A4
• electric medical record
• fluvastatin
• lovastatin
• simvastatin

Declaration of interest

This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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