pitavastatin and Rhabdomyolysis

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely prescribed therapeutic class of drugs worldwide, with established clinical benefits both in terms of improving serum lipid profiles and reducing cardiovascular events and mortality. Although statins have a favorable risk-to-benefit ratio, they have the potential to cause adverse events which can result in muscular inflammation (myositis), muscle breakdown (rhabdomyolysis) and, ultimately, kidney failure. While the incidence of rhabdomyolysis is approximately 3.4 cases per 100,000 person-years with standard-dose statin therapy, the risk of developing the condition increases substantially at higher therapeutic doses. This effect may be exacerbated by prescribing statins in combination with certain other medications because drug � drug interactions increase statin exposure by interacting with enzymes that would normally be involved in their metabolism and clearance. Co-administration of drugs that inhibit the cytochrome P450 (CYP) enzymes responsible for metabolizing statins, or that interact with the organic anion-transporting polypeptides (OATPs) responsible for statin uptake into hepatocytes, substantially increases the risk of developing myotoxicity. Such effects vary among statins according to their metabolic profile. For example, pitavastatin, a novel statin approved for the treatment of hypercholesterolemia and combined (mixed) dyslipidemia, is not catabolized by CYP3A4, unlike other lipophilic statins, and may be less dependent on the OATP1B1 transporter for its uptake into hepatocytes before clearance. Such differences in drug � drug interaction profiles among available statins offer the possibility of reducing the risk of myotoxicity among high-risk patients.

Topics: Cardiovascular Diseases; Dose-Response Relationship, Drug; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lipids; Quinolines; Rhabdomyolysis; Risk

There are many speculations about the safety of statins which are widely used drugs. In contrast, statins are safer than many widely used drugs. Rhabdomyolysis, the most important adverse event is closely related to plasma drug levels which take drug interactions into account. The most important drugs among interacting drugs are fibrates, antiretroviral drugs and macrolid antibiotics, and, pitavastatin seems to be more advantageous than other statins. Similarly, pitavastatin has better myopathy profile when compared to other statins. Hepatotoxicity, cancer risk and adverse cognitive effects are very rare with statins and pitavastatin is as safer as other statins in terms of these adverse events.

Topics: Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quinolines; Rhabdomyolysis