title: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacological Sciences, University of Milan, Italy. alberto.corsini@unimi.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Corsini
authors.forename: Richard
authors.initials: R
authors.lastname: Ceska
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D039781:PubMed; D011804:Quinolines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D003577:Cytochrome P-450 Enzyme System; C108475:pitavastatin