Original Title: Pharmacocinétique, efficacité, innocuité et persistance au traitement avec les versions génériques de Concerta comparativement à Concerta

Authors' objectives: Since the approval and marketing of Concerta™ in 2003, four generic versions have also been approved by Health Canada: three generic versions without the OROS release system (non-OROS), namely Novo-Methylphenidate ER-C™ (renamed ACTMethylphenidate ER™), Apo-Methylphenidate ER™ and pms-Methylphenidate ER™ (discontinued), as well as one generic version with the OROS system (TaroMethylphenidate ER™). Currently, only two generic products are marketed in Canada: the non-OROS generics ACT-Methylphenidate ER™ and Apo-Methylphenidate ER™. It should also be noted that during the evaluation process for reimbursement by the Conseil du médicament, differences between Concerta™ and the non-OROS generic versions were observed in certain pharmacokinetic parameters that could potentially compromise clinical efficacy and safety, especially when switching from the innovator product to the generic product. In order to verify the availability of new scientific data to document the clinical effects of pharmacokinetic differences between Concerta™ and its generic versions, the Institut national d’excellence en santé et en services sociaux (INESSS) undertook to update the previously published state of knowledge on the subject.

Authors' results and conclusions: RESULTS (#1 PHARMACOKINETICS): The published pharmacokinetic data of generic versions available in Canada in 2024 are similar to those of Concerta™ according to Health Canada's bioequivalence requirements (Cmax, AUC0-t and AUC0-inf). However, the values of predefined partial AUCs were not available in the product monographs. (#2 EFFICACY): Switching from Concerta™ to a non-OROS generic version (NovoMethylphenidate ER-C™ in Canada or Methylphenidate ER™ in the United States) could lead to destabilization of patients' condition and potential return of ADHD symptoms (low and insufficient level of scientific evidence). (#3 SAFETY): Adverse effects such as exacerbation of ADHD symptoms, problems associated with drug substitution, fatigue, nausea, and sleep problems were noted in pharmacokinetic studies and studies on switching from Concerta™ to its generic versions. Despite the low level of scientific evidence, the number of adverse effects observed is sometimes higher in adults with ADHD who switched from Concerta™ to Novo-Methylphenidate ER-C™ compared to patients who continued with Concerta™. (#4 PERSISTENCE OF TREATMENT ADHERENCE): The persistence rate of treatment adherence was lower for the generic version Novo-Methylphenidate ER-C™ than for maintaining treatment with Concerta™ (moderate level of evidence). (#5 REIMBURSEMENT MODALITIES AND INTERCHANGEABILITY): The reimbursement of the innovator Concerta™ by the public insurance system in Canada varies from province to province according to the following coverages: fully covered (five provinces), covered at the generic price (four provinces) and not covered (one province). The non-OROS generic versions ACTMethylphenidate ER™ and Apo-Methylphenidate ER™ are fully reimbursed in all ten Canadian provinces. CONCLUSION: Although the generic versions Apo-Methylphenidate ER™, ACT-Methylphenidate ER™ and Taro-Methylphenidate ER™ are considered by Health Canada to be bioequivalent to Concerta™, the data published to date are insufficient to determine their therapeutic equivalence profile compared to Concerta™. The data available in 2024 on pharmacokinetic parameters as well as on the change in clinical status and persistence of treatment adherence when switching from Concerta™ to a non-OROS generic version of Concerta™ do not seem to show complete therapeutic equivalence.

Authors' methods: SYSTEMATIC LITERATURE REVIEW: To evaluate the pharmacokinetics, efficacy, safety, and persistence of treatment adherence, a systematic review was conducted using multiple databases published between 1997 and 2024. Document selection was performed according to predefined exclusion and inclusion criteria. The quality of selected documents was assessed using appropriate tools. These steps were conducted independently by two scientific professionals. Data were then extracted by one scientific professional and validated by another. Results were presented in tables and summarized in the form of an analytical narrative synthesis. The reimbursement modalities for Concerta™ and its generic versions in Canadian provinces were added to the original work and are presented as a narrative review. SCIENTIFIC EVIDENCE APPRAISAL PROCESS: The main results on pharmacokinetics, efficacy, safety, and persistence of treatment adherence reported in the selected studies were formulated as summarized scientific evidence statements. An overall level of scientific evidence was assigned to each statement, according to a four-level scale (high, moderate, low, insufficient).

Project Status: Completed

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/fileadmin/doc/INESSS/Rapports/ServicesSociaux/INESSS_Pharmacocinetique_Concerta.pdf

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)