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This Article Full Text Full Text (PDF) CME: Take the course for this article: Volume 72, Number 24, June 16, 2009 Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Duh, M. S. Articles by LeLorier, J. PubMed Articles by Duh, M. S. Articles by LeLorier, J. Related Collections Cost effectiveness/economic Outcome research Cohort studies All Epilepsy/Seizures Antiepileptic drugs

The risks and costs of multiple-generic substitution of topiramate

From the Analysis Group, Inc. (M.S.D., P.E.G.), Boston, MA; Groupe d'Analyse, Ltée (P.E.P., D.L.-V.), Montréal, Québec, Canada; Johnson & Johnson Pharmaceutical Services (S.P.L.), LLC, Horsham, PA; Ortho-McNeil Janssen Scientific Affairs (M.B.D., G.J.W.), LLC, Titusville, NJ; Ethicon, Inc. (M.F.T.R.), Somerville, NJ; and Centre Hospitalier de l'Université de Montréal (CHUM) (J.L.), Montréal, Québec, Canada.

Address correspondence and reprint requests to Dr. Mei Sheng Duh, Vice President, Analysis Group, Inc., 111 Huntington Avenue, Tenth Floor, Boston, MA 02199 mduh{at}analysisgroup.com.

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).

Conclusion: Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Abbreviations: AED = antiepileptic drug; C$ = constant Canadian dollars; CD = cost difference; CI = confidence interval; CR = cost ratio; HR = hazard ratio; ICD = International Classification of Diseases; IRD = incidence rate difference; IRR = incidence rate ratio; NTI = narrow therapeutic index; RAMQ = Régie de l'Assurance-Maladie du Québec.

Medications: carbamazepine (Tegretol; Novartis, Basel, Switzerland); clobazam (Frisium; Sanofi-Aventis, Paris, France); clonazepam (Rivotril; Roche, F. Hoffmann–La Roche, Basel, Switzerland); divalproex (Epival) and valproate (Depakene) (Abbott Laboratories, Abbott Park, IL); fosinopril (Monopril) and pravastatin (Pravachol) (Bristol-Myers Squibb, New York, NY); gabapentin (Neurontin; Pfizer, New York, NY); isosorbide (Imdur; AstraZeneca, London, UK); lamotrigine (Lamictal; GlaxoSmithKline, Brentford, UK); topiramate (Topamax; Ortho-McNeil Neurologics, Titusville, NJ); venlafaxine (Effexor; Wyeth, Madison, NJ).

Disclosure: Author disclosures are provided at the end of the article.

Received September 8, 2008. Accepted in final form March 13, 2009.

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