title: The risks and costs of multiple-generic substitution of topiramate.
abstract: OBJECTIVE
  To investigate clinical and economic consequences following generic substitution of one vs multiple generics of topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ).
  
  
  METHODS
  Medical and pharmacy claims data of Régie de l'Assurance-Maladie du Québec from January 2006 to October 2007 were used. Patients with epilepsy treated with topiramate were selected. An open-cohort design was used to classify the observation period into periods of brand, single-generic, and multiple-generic use. One-year generic-switch and switchback-to-brand rates were estimated using Kaplan-Meier methodology. Medical resource utilization and costs were compared among the three periods using multivariate regression analysis.
  
  
  RESULTS
  In total, 948 patients were observed during 1,105 person-years of brand use, 233 person-years of single-generic use, and 92 person-years of multiple-generic use. A total of 23% of generic users received at least two different generic versions. Compared to brand use, multiple-generic use was associated with higher utilization of other prescription drugs (incidence rate ratio [IRR] = 1.27, 95% confidence interval [CI] = 1.24-1.31), higher hospitalization rates (0.48 vs 0.83 visit/person-year, IRR = 1.65, 95% CI = 1.28-2.13), and longer hospital stays (2.6 vs 3.9 days/person-year, IRR = 1.43, 95% CI = 1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: IRR = 1.08, 95% CI = 0.88-1.34, length of stay: IRR = 1.12, 95% CI = 1.03-1.23). The risk of head injury or fracture was nearly three times higher (hazard ratio = 2.84, 95% CI = 1.24-6.48) following a generic-to-generic switch compared to brand use. The total annualized health care cost per patient was higher in the multiple-generic than brand periods by C$1,716 (cost ratio = 1.21, p = 0.0420).
  
  
  CONCLUSIONS
  Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.
authors.affiliation: Analysis Group, Inc., Boston, MA 02199, USA. mduh@analysisgroup.com
authors.forename: M S
authors.initials: MS
authors.lastname: Duh
authors.forename: P E
authors.initials: PE
authors.lastname: Paradis
authors.forename: D
authors.initials: D
authors.lastname: Latrémouille-Viau
authors.forename: P E
authors.initials: PE
authors.lastname: Greenberg
authors.forename: S P
authors.initials: SP
authors.lastname: Lee
authors.forename: M B
authors.initials: MB
authors.lastname: Durkin
authors.forename: G J
authors.initials: GJ
authors.lastname: Wan
authors.forename: M F T
authors.initials: MF
authors.lastname: Rupnow
authors.forename: J
authors.initials: J
authors.lastname: LeLorier
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D002908:Chronic Disease / Q000188:drug therapy; D015331:Cohort Studies; D015897:Comorbidity; D006259:Craniocerebral Trauma / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016527:Drug Costs / Q000706:statistics & numerical data / Q000639:trends; D004363:Drug Utilization / Q000191:economics; D016568:Drugs, Generic / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology*; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000191:economics; D006264:Health Benefit Plans, Employee / Q000191:economics; D017048:Health Care Costs / Q000706:statistics & numerical data / Q000639:trends; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007349:Insurance, Health, Reimbursement / Q000191:economics; D008297:Male; D010342:Patient Acceptance of Health Care; D016016:Proportional Hazards Models; D011792:Quebec; D012189:Retrospective Studies; D012307:Risk Factors; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D016568:Drugs, Generic; D000077236:Topiramate; D005632:Fructose