Abstract
Purpose
The purpose of this study was to measure the rate of substitution failure to generic antiepileptic drugs (AEDs) compared to two other pharmacotherapeutic classes (neuroleptics, beta-blockers).
Methods
We conducted a cohort study involving beneficiaries of the French health insurance system from January 2009 to November 2012. Substitution failure to generic drugs was estimated by the rate of switchback (i.e. from generic drug back to its branded drug). We selected the patients who had a dispensation of a branded AED for 60 days or more during the 90 days preceding the generic substitution. Cox proportional hazard regression was used to model time to switchback for antiepileptics vs. other therapeutic classes in the 90 days after generic substitution, adjusting for age, gender and polytherapy.
Results
The cohort included 6727 patients of whom 1947 were exposed to AEDs, 2398 to neuroleptics and 2382 to beta-blockers. The switchback rate was 62% for AEDs. AED users were more likely to switch back as compared to beta-blocker (crude hazard ratio 1.87; 95% CI 1.68–2.07 for patients under 75) or neuroleptic users. The same observation was made in patients above 75 years (crude hazard ratio 1.36; 95% CI 1.16–1.60).
Conclusions
Compared to beta-blocker users, AED users were more likely to switch back to the branded drug, whereas this difference was not observed with neuroleptics. These results could reflect a poor acceptance of switching AEDs to generic compounds in France.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Berg MJ, Gross RA, Tomaszewski KJ et al (2008) Generic substitution in the treatment of epilepsy: case evidence of breakthrough seizures. Neurology 71:525–530. doi:10.1212/01.wnl.0000319958.37502.8e
Gauzit R, Lakdhari M (2012) Generic antibiotic drugs: is effectiveness guaranteed? Med Mal Infect 42:141–148
Committee for Medicinal Products for Human Use. Guideline on the investigation of bioequivalence. CPMP/EWP/QWP/1401/98 Rev.1/Corr**2010 http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf. Accessed 5 december 2016.
Krauss GL, Caffo B, Chang Y-T et al (2011) Assessing bioequivalence of generic antiepilepsy drugs. Ann Neurol 70:221–228. doi:10.1002/ana.22452
Kesselheim AS, Stedman MR, Bubrick EJ et al (2010) Seizure outcomes following the use of generic versus brand-name antiepileptic drugs. Drugs 70:605–621. doi:10.2165/10898530-000000000-00000
Talati R, Scholle JM, Phung OP et al (2012) Efficacy and safety of innovator versus generic drugs in patients with epilepsy: a systematic review. Pharmacotherapy 32:314–322. doi:10.1002/j.1875-9114.2012.01099.x
Vari MS, Pinto F, Mencaroni E et al (2016) Safety of overnight switch from brand-name to generic levetiracetam. Clin Drug Investig 36:87–91. doi:10.1007/s40261-015-0351-1
LeLorier J, Duh MS, Paradis PE et al (2008) Clinical consequences of generic substitution of lamotrigine for patients with epilepsy. Neurology 70:2179–2186. doi:10.1212/01.wnl.0000313154.55518.25
Andermann F, Duh MS, Gosselin A, Paradis PE (2007) Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes. Epilepsia 48:464–469. doi:10.1111/j.1528-1167.2007.01007.x
Martin-Latry K, Bégaud B (2010) Pharmacoepidemiological research using French reimbursement databases: yes we can! Pharmacoepidemiol Drug Saf 19:256–265. doi:10.1002/pds.1912
Prévalences des ALD, 2012. http://www.ameli.fr/fileadmin/user_upload/documents/Prevalences_2012_mise_en_garde.pdf. Accessed 28 Sep 2016
Imbaud D, Morin A, Picard S, Toujas F (2012) Evaluation de la politique française des médicaments génériques. http://leciss.org/sites/default/files/Rapport%20IGAS_medicaments%20generiques_2012.pdf. Accessed 26 September 2016.
Olesen C, Harbig P, Barat I, Damsgaard EM (2013) Generic substitution does not seem to affect adherence negatively in elderly polypharmacy patients. Pharmacoepidemiol Drug Saf 22:1093–1098
Latry P, Molimard M, Bégaud B, Martin-Latry K (2010) How reimbursement databases can be used to support drug utilisation studies: example using the main French national health insurance system database. Eur J Clin Pharmacol 66:743–748. doi:10.1007/s00228-010-0819-0
Noize P, Bazin F, Dufouil C et al (2009) Comparison of health insurance claims and patient interviews in assessing drug use: data from the Three-City (3C) Study. Pharmacoepidemiol Drug Saf 18:310–319. doi:10.1002/pds.1717
Rathe J, Andersen M, Jarbøl DE et al (2015) Generic switching and non-persistence among medicine users: a combined population-based questionnaire and register study. PLoS One 10:e0119688. doi:10.1371/journal.pone.0119688
Durrieu G, Batz A, Rousseau V et al (2014) Use of administrative hospital database to identify adverse drug reactions in a pediatric university hospital. Eur J Clin Pharmacol 70:1519–1526. doi:10.1007/s00228-014-1763-1
Rathe J, Larsen P, Andersen M et al (2013) Associations between generic substitution and patients’ attitudes, beliefs and experiences. Eur J Clin Pharmacol 69:1827–1836. doi:10.1007/s00228-013-1539-z
Sommet A, Georgel B, Poutrain J-C et al (2013) Différences de taux de substitution des médicaments génériques en Midi-Pyrénées en fonction des classes pharmaco-thérapeutiques. Revue d’Épidémiologie et de. Santé Publique 61:539–544. doi:10.1016/j.respe.2013.08.001
Wise J (2015) Doctors are warned not to prescribe generic pregabalin for pain control. BMJ 350:h1724–h1724. doi:10.1136/bmj.h1724
Dylst P, Vulto A, Simoens S (2013) Demand-side policies to encourage the use of generic medicines: an overview. Expert Rev Pharmacoecon Outcomes Res 13:59–72. doi:10.1586/erp.12.83
Kesselheim AS (2013) Variations in pill appearance of antiepileptic drugs and the risk of nonadherence. JAMA Intern Med 173:202. doi:10.1001/2013.jamainternmed.997
Acknowledgements
We would like to thank the direction of medical services of the National Health Insurance Fund for Salaried Workers for the Midi-Pyrénées area (DRSM-CNAMTS).
Authors’ contributions
All the authors have participated in the study design. AM, AP and VR analysed the data. AM, AP and HB wrote the first draft of the manuscript. All the authors participated in the result interpretation and have read and approved the final version of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Ethical approval
The project was not a biomedical research project and therefore did not need the Research Ethics Committee’s approval. The anonymity of patients was strictly preserved throughout the data entry and analysis process.
Rights and permissions
About this article
Cite this article
Molinier, A., Palmaro, A., Rousseau, V. et al. Does substitution of brand name medications by generics differ between pharmacotherapeutic classes? A population-based cohort study in France. Eur J Clin Pharmacol 73, 471–477 (2017). https://doi.org/10.1007/s00228-016-2185-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-016-2185-z