Statins are well established as first-line agents for LDL-cholesterol lowering therapy to prevent cardiovascular diseases. However, statin therapy may cause myopathy, including rhabdomyolysis, the risk of which is increased by certain interactions. Cerivastatin has caused hundreds of cases of rhabdomyolysis, especially when administered concomitantly with gemfibrozil; and it was eventually withdrawn from the market. In general, significant myopathy is rare with an incidence of less than 0.5% of patients, and statins are safety drugs and well tolerable. Statin side effects may be dose related; due in part to the drug-drug interactions. Cerivastatin drug interactions are involved in CYP3A4, CYP2C8, and organic anion transporting polypeptide (OATP). Recently, common variants in SLCO1B1, encoding OATP1B1, have been reported to be closely related to the increased risk of statin-induced myopathy. The development of pharmacogenetics (PGx) can help to promote drug usefulness and reduce side effects including the drug-drug interactions. Alternatively, careful medical care by physicians, employing precise, rapid information provision for serious adverse effects, including black box warning, and the establishment of a proper post-marketing surveillance system are important for preventing serious adverse drug effects and should also be performed proactively.
View full abstract