title: Persistent use of against-label statin-fibrate combinations from 2003-2009 despite United States Food and Drug Administration dose restrictions.
abstract: OBJECTIVE
  To describe the prevalence of prescribing against-label statin-fibrate combination therapy.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Medstat MarketScan Commercial Claims and Encounter database.
  
  
  METHODS
  Adults (aged 18-89 yrs) who were prescribed statin-fibrate combination therapy between January 1, 2003, and June 30, 2009, had pharmacy claims demonstrating two or more concurrently filled prescriptions for a statin and a fibrate, and had continuous insurance enrollment for at least 12 months.
  
  
  RESULTS
  Claims data were used to identify patients with dyslipidemia based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. National Drug Codes were used to describe concurrent statin-fibrate combination therapy. The primary outcome was recent use of against-label statin-fibrate combination therapy, defined as use during the last 18 months (January 1, 2008-June 30, 2009) of the study period. Patients were stratified according to statin and dosage to identify against-label combination use (e.g., simvastatin > 10 mg/day with gemfibrozil). Within the recent-use period, 131,394 patients were prescribed concurrent statin-fibrate combination therapy; of these patients, 13,420 (10.2%) had against-label therapy. Simvastatin-gemfibrozil accounted for 8978 (66.9%) of all against-label combinations. Of all 9877 simvastatin-gemfibrozil combinations prescribed in the recent-use period (both on-label and against-label use), 8978 (90.9%) were against label. The secondary outcome was prevalence of against-label statin-fibrate combination therapy on an annual basis: 15.5% in 2003, 18.7% in 2004, 9.1% in 2005, 8.3% in 2006, 9.2% in 2007, and 9.8% in 2008.
  
  
  CONCLUSIONS
  Against-label statin-fibrate combination therapy continues to be prescribed despite established United States Food and Drug Administration (FDA) dose restrictions. Nearly every time the simvastatin-gemfibrozil combination was prescribed, it was against label because simvastatin exceeded the maximum dose restriction. Updated simvastatin labeling in June 2011 includes additional maximum dose restrictions and new contraindications, which include gemfibrozil. Different approaches in clinical practice are needed to ensure adherence with the revised FDA labeling.
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Alford
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Saseen
authors.forename: Richard R
authors.initials: RR
authors.lastname: Allen
authors.forename: Kavita V
authors.initials: KV
authors.lastname: Nair
mesh_terms: D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004348:Drug Labeling; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy; D005260:Female; D058607:Fibric Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D015248:Gemfibrozil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use / Q000706:statistics & numerical data*; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data; D012189:Retrospective Studies; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D019821:Simvastatin; D015248:Gemfibrozil