Original Contribution
A clinician's guide to statin drug-drug interactions

https://doi.org/10.1016/j.jacl.2014.02.010Get rights and content

Highlights

  • After reading the article, the practitioner will:

  • ►

    Better understand the different enzyme systems involved in statin metabolism and intrapatient differences.

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    Be able to predict potential drug interactions based on changes in the area under the curve for statin concentrations.

  • ►

    Be able to better interpret package labeling with respect to drug-drug interactions.

  • ►

    Identify common prescription and nonprescription medications that interact with statins.

  • ►

    Identify special populations that may be at risk for statin drug-drug interactions.

Abstract

The statins are widely used worldwide to reduce risk for cardiovascular events in both the primary and secondary prevention settings. Although generally quite safe, the statins can be associated with a variety of serious side adverse effects, including myalgia, myopathy, and changes in plasma enzymes of hepatic origin. Although rare, the most serious of these is rhabdomyolysis. Several drugs can interfere with the metabolism and disposal of the statins, thereby increasing risk for adverse events. It is important that clinicians treating patients with statins be aware of the potential for drug-drug interactions between each statin and specific other drugs and take measures to prevent them. The prediction of potential drug-drug interactions derives from basic pharmacokinetic principles. Certain drug interactions are predicted by measuring the effect of interacting drugs on blood plasma concentrations of the statin. Individual patient variations resulting in part from polymorphisms in the metabolizing enzymes confound some of these predictions. Based on these known effects, a new classification for predicting statin drug interactions is proposed. This report discusses likely prescription and nonprescription interactions as well as potential alternatives for special populations.

Section snippets

Individual variation in enzyme induction, inhibition, and patient response

Although traditional models attribute statin metabolism to the cytochrome hepatic systems, more contemporary theories involve classification of potential pathways as follows:

  • a

    lipophilic lactone prodrugs such as simvastatin are predominantly CYP metabolized;

  • b

    polar statins such as rosuvastatin and pravastatin are substrates of transporters including the hepatic OATPs, sodium/taurocholate cotransporting peptides (NTCP), and the renal OATPs; and

  • c

    statins such as fluvastatin that are metabolized by CYP

Conclusions

Statin absorption, distribution, metabolism, and excretion are complex and vary from statin to statin. The transporters and enzymes involved in these processes are now better understood and serve to explain the mechanisms of statin interactions with a variety of drugs that alter what is otherwise an excellent safety profile. As new drugs enter the US market, understanding these mechanisms allows the clinician to predict the impact new drugs may have on statin disposition, given the effect of a

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    Disclosures: Dr Bottorff and Dr Toth disclose that they have relationships with industry that might pose a potential conflict of interest. Dr Bottorff has received honoraria for serving as a speaker and/or consultant to AstraZeneca, Bristol-Myers Squibb, Sanofi, Boehringer Ingelheim, and Pfizer. Dr Toth is on the speaker bureaus for AbbVie, Amarin, AstraZeneca, Genzyme, Kowa, and Merck, and has served as a consultant to Amgen, Atherotech, Genzyme, Kowa, LipoScience, and Merck. Dr Kellick has no financial relationships with commercial entities producing health care goods or services.

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    Published by Elsevier Inc.