title: Co-medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy.
abstract: BACKGROUND
  HMG-CoA reductase inhibitors (statins) are frequently used drugs in the treatment of dyslipidaemia. Co-medication with interacting drugs increases the risk of statin-induced muscular side-effects. Simvastatin exhibits particularly high interaction potential due to substantial metabolism via cytochrome P450 3A4 (CYP3A4).
  
  
  CONCLUSIONS
  In June 2005, a new reimbursement policy was introduced by the Norwegian Medicines Agency stating that simvastatin should be prescribed as first-line lipid-lowering therapy. Following introduction of the new policy, the number of patients co-medicated with simvastatin and CYP3A4 inhibitors almost doubled. A potential consequence is increased incidence of muscular side-effects in the statin-treated population.
  
  
  OBJECTIVE
  To assess the prevalence of co-medication of statins and CYP3A4 inhibitors before and after introduction of a new Norwegian reimbursement policy, which states that all patients should be prescribed simvastatin as first-line lipid-lowering therapy.
  
  
  METHODS
  Data from patients receiving simvastatin, lovastatin, pravastatin, fluvastatin or atorvastatin in 2004 and 2006, including co-medication of potent CYP3A4 inhibitors, were retrieved from the Norwegian Prescription Database covering the total population of Norway. Key measurements were prevalence of continuous statin use (two or more prescriptions on one statin) and proportions of different statin types among all patients and those co-medicated with CYP3A4 inhibitors.
  
  
  RESULTS
  In 2004, 5.9% (n= 272 342) of the Norwegian population received two or more prescriptions on one statin compared with 7.0% (n= 324 267) in 2006. The relative number of simvastatin users increased from 39.7% (n= 112 122) in 2004 to 63.1% (n= 226 672) in 2006. A parallel increase was observed within the subpopulation co-medicated with statins and CYP3A4 inhibitors, i.e. from 42.9% (n= 7706) in 2004 to 63.6% (n= 13 367) in 2006. For all other statins the number of overall users decreased to a similar extent to those co-medicated with CYP3A4 inhibitors.
  
  
  CONCLUSIONS
  In both 2004 and 2006, the choice of statin type did not depend on whether the patient used a CYP3A4 inhibitor or not. Considering the pronounced interaction potential of simvastatin with CYP3A4 inhibitors, a negative influence of the new policy on overall statin safety seems likely.
authors.affiliation: Department of Pharmacoepidemiology, Norwegian Institute of Public Health, P.b. 4404 Nydalen, Oslo, Norway. helene.devold@fhi.no
authors.forename: Helene M
authors.initials: HM
authors.lastname: Devold
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
authors.forename: Svetlana
authors.initials: S
authors.lastname: Skurtveit
authors.forename: Kari
authors.initials: K
authors.lastname: Furu
mesh_terms: D000924:Anticholesteremic Agents / Q000191:economics* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D051544:Cytochrome P-450 CYP3A / Q000191:economics*; D065692:Cytochrome P-450 CYP3A Inhibitors; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000191:economics* / Q000494:pharmacology; D009664:Norway; D010818:Practice Patterns, Physicians' / Q000191:economics / Q000592:standards; D012051:Reimbursement Mechanisms; D019821:Simvastatin / Q000191:economics* / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human