Drug–drug interactions with statins: will pitavastatin overcome the statins’ Achilles’ heel?

Abstract

Background:

As the clinical complexity of patients at high cardiovascular risk and with multiple comorbid conditions increases, so does the potential for drug–drug interactions (DDIs). Large retrospective studies in various clinical settings have shown that an unacceptably large proportion of patients are coprescribed a statin with potentially interacting therapies, suggesting that the impact of polypharmacy on the safety profile of statins may be underappreciated.

Scope:

To assess the evidence for the burden of DDIs and related adverse drug reactions (ADRs) with current statins relative to pitavastatin, a new agent recently approved in the USA and EU.

Methods:

Structured review of the PubMed and EMBASE databases (to 15 October 2010) for literature on statins in the areas of ADRs, polypharmacy and DDIs; pharmacokinetics, and pitavastatin clinical safety and efficacy.

Findings:

Patients who are on statin therapy are often receiving multiple medications for comorbid conditions, and so are at increased risk of ADRs, such as myopathy, because of pharmacokinetic interactions at the level of cytochrome P450 (CYP) enzymes and/or organic anion-transporting polypeptides. Pitavastatin has a distinctive metabolic profile that means it is marginally metabolised by CYP enzymes, and is therefore expected to have a low risk of DDIs and related ADRs. A large post-marketing study conducted in more than 20,000 patients in Japan has demonstrated that the rate of DDIs with pitavastatin treatment may compare favourably with that observed with atorvastatin and rosuvastatin.

Conclusions:

The addition of pitavastatin to the range of available statins provides prescribing physicians with a new treatment option that is expected to have a low risk of DDIs and related ADRs. This, coupled with the demonstrated efficacy of pitavastatin in reducing low-density lipoprotein cholesterol, should help physicians individualise lipid-lowering regimens based on the patient profile and concomitant medications.

Key words::

• Adverse drug reactions
• Drug–drug interactions
• Pitavastatin
• Polypharmacy
• Statins

Transparency

Declaration of funding

Both authors participated in the development and writing of the paper, and approved the final manuscript for publication. Kowa Pharmaceutical Europe Co. Ltd provided review of the final manuscript for scientific accuracy but had no part in the decision to submit the final manuscript.

Declaration of financial/other relationships

A.C. has disclosed that he has received research grants and/or honoraria from, or has been a consultant for, Merck and Co., Merck-Schering Plough, NiCox, Novartis, Roche, Pfizer Inc., Kowa, Regeneron, Recordati and sanofi-aventis. R.C. has disclosed that he has received research grants and/or honoraria from, or has been a consultant for, Abbott, Merck and Co., Merck-Schering Plough, Pfizer Inc., Kowa, Krka and sanofi-aventis.

Acknowledgements

The authors take full responsibility for the content of the paper and would like to thank Dr Richard White (Oxford PharmaGenesis™Ltd) for carrying out literature searches on DDIs and ADRs with statins, providing the authors with an overview of the search findings, and collating and incorporating comments from all authors. This editorial assistance was funded by Kowa Pharmaceutical Europe Co. Ltd.