Clinical conundrums involving statin drug-drug interactions

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.