title: Muscle symptoms in statin users, associations with cytochrome P450, and membrane transporter inhibitor use: a subanalysis of the USAGE study.
abstract: BACKGROUND
  Drug interactions have been identified as a risk factor for muscle-related side effects in statin users.
  
  
  OBJECTIVE
  The aim was to assess whether use of medications that inhibit cytochrome P450 (CYP450) isozymes, organic anion transporting polypeptide 1B1 (OATP1B1), or P-glycoprotein (P-gp) are associated with muscle-related symptoms among current and former statin users.
  
  
  METHODS
  Persons (n = 10,138) from the Understanding Statin Use in America and Gaps in Education (USAGE) internet survey were categorized about whether they ever reported new or worsening muscle pain while taking a statin (n = 2935) or ever stopped a statin because of muscle pain (n = 1516). Univariate and multivariate logistic regression models were used to assess associations between use of concomitant therapies that inhibit CYP450 isozymes, OATP1B1, P-gp, or a combination and muscle-related outcomes.
  
  
  RESULTS
  In multivariate analyses, concomitant use of a CYP450 inhibitor was associated with increased odds for new or worse muscle pain (odds ratio [OR] = 1.42; P < .001) or ever having stopped a statin because of muscle pain (OR = 1.28; P = .037). Concomitant use of medication known to inhibit both OATP1B1 and P-gp was also associated with increased odds (OR = 1.80; P = .030) of ever having stopped a statin because of muscle pain.
  
  
  CONCLUSIONS
  Concomitant use of medication(s) that inhibit statin metabolism was associated with increased odds of new or worse muscle pain while taking a statin and having previously stopped a statin because of muscle symptoms. These data emphasize the importance of enhancing the capabilities of clinicians and health systems for identifying and reducing statin drug interactions.
authors: Oregon State University/Oregon Health & Science University College of Pharmacy, 3303 SW Bond Avenue, Portland, OR 97239, USA. Electronic address: itom@ohsu.edu.
authors: Matthew K
authors: MK
authors: Ito
authors: Biofortis Clinical Research, Addison, IL 60101, USA.
authors: Kevin C
authors: KC
authors: Maki
authors: Utah Foundation for Biomedical Research, Salt Lake City, UT 84106, USA.
authors: Eliot A
authors: EA
authors: Brinton
authors: St. Louis University School of Medicine, St. Louis, MO 63105, USA.
authors: Jerome D
authors: JD
authors: Cohen
authors: Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Terry A
authors: TA
authors: Jacobson
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003710:Demography; D005260:Female; D006266:Health Education; D006306:Health Surveys; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009132:Muscles / Q000187:drug effects / Q000473:pathology*; D063806:Myalgia / Q000139:chemically induced*; D014481:United States
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D026901:Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; Discontinuation; Drug interactions; Muscle pain; Myopathy; OATP1B1; P-glycoprotein; Statins