Elsevier

Progress in Cardiovascular Diseases

Volume 75, November–December 2022, Pages 83-89
Progress in Cardiovascular Diseases

Clinical conundrums involving statin drug-drug interactions

https://doi.org/10.1016/j.pcad.2022.11.002Get rights and content

Abstract

Statins are the cornerstone of pharmacologic therapy for the prevention and treatment of atherosclerotic cardiovascular disease. While they are generally considered safe, statins can be affected by drug-drug interactions (DDIs) that increase their systemic exposure increasing the risk for statin-associated muscle symptoms. These interactions are primarily mediated through metabolizing enzymes such as cytochrome P450 isoenzymes and membrane-bound drug transporting proteins including P-glycoprotein and organic ion transporting polypeptide. Recognition and avoidance of clinically significant statin DDIs is important to ensure their safe use. Conversely, concern over statin DDIs that are not clinically significant may lead to inappropriate underutilization or avoidance of statins in patients who would benefit from them. While many statin DDIs are well-characterized, we present several others that are less-well-established which may warrant clinical attention.

Section snippets

Specific statin drug-drug interactions

The National Lipid Association Scientific Statement on Statin Intolerance cites statin DDIs as a key modifiable risk factor for preventing statin-associated muscle symptoms.4 The medical literature is replete with many statin DDIs that are well-characterized (e.g. gemfibrozil, calcium channel blockers, azole antifungals) with clear recommendations by the manufacturer, U.S. Food and Drug Administration (FDA), or professional society guidelines on how to address them.6 Recommendations range from

Conclusions

The underlying mechanisms of statin DDIs are multifaceted, and many common medications have an extensive evidence base and consensus opinions that explain these interactions and provide guidance to clinicians. However, there are statin DDIs that are particularly challenging and are less-well-established and may warrant clinical attention. Ritonavir (combined with nirmatrelvir), daptomycin, tacrolimus, and amiodarone are older medications that are known to have different degrees of DDI with

Disclosures

None.

Funding

None.

Declaration of Competing Interest

None.

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