Avoiding statin myopathy: understanding key drug interactions

Abstract

Statin interaction with other drugs may play an important role in statin myopathy. Clinician familiarity with statin metabolism, pharmacokinetics and drugs that commonly interact with statins may reduce the incidence of muscle.related side effects. The dose of a statin is frequently related to statin myopathy. Many drugs including simvastatin, lovastatin and atorvastatin are metabolized by the CYP3A4 isoenzyme system. This article reviews commonly prescribed drugs that are potent inhibitors of the CYP3A4 system. We also review statin cell membrane drug transporters including OATP and MDR1 that have also been shown to play a key role in statin metabolism and drug interactions. There is now a growing list of drugs known to inhibit the activity of these transporters. In this review, we highlight three key populations at an increased risk for statin drug interactions including patients receiving treatment for mixed dyslipidemia, HIV and chronic kidney disease. We discuss treatment strategies for use in these high-risk populations. An understanding of statin pharmacokinetics, metabolism by the CYP450 system, and uptake or elimination by cell membrane transporters, helps explain many of the drug interactions that lead to statin myopathy.

Keywords:

• cytochrome P450
• drug interaction
• HMG-CoA reductase inhibitor
• MDR1 n multidrug resistance protein
• myalgia
• myopathy
• OATP1B1
• organic anion transporter protein
• rhabdomyolysis
• statin-induced myopathy
• statins
• transporter protein