Abstract
Purpose
The objective of this study was to determine whether the so-called “shift” or “drift” problem might occur when generic anti-epileptic drugs are interchanged, and thus to assess if generic anti-epileptic drugs are interchangeable and can be used in an efficacious and safe way on the basis of their bioequivalence to one and the same reference product.
Methods
The bioequivalence of topiramate and gabapentin generics was evaluated. For proper interstudy comparison, individual exposure data (AUC and Cmax) for each bioequivalence study present in the registration dossier was normalized based on the absolute exposure data of one of two innovators. The exposure-normalized plasma concentration curves of the generic product arms between studies were compared, providing indirect evidence of bioequivalence of the different generics. Additionally, comparisons were made for generic–generic as well as innovator–innovator exchange based on absolute exposure data from individual bioequivalence studies.
Results
In almost all cases, estimated 90% confidence intervals of the AUC and Cmax ratios for generic–generic interchange were within the routine 80–125% criterion. When absolute, non-corrected exposure data were used for this interstudy comparison, in a number of cases 90% confidence intervals outside the 80–125% criterion were found upon interchanging generics from two studies. However, a similar pattern of 90% confidence intervals outside the 80–125% criterion was observed for the comparison of innovator arms, despite the fact that the innovator was identical in all studies.
Conclusion
Our results strongly indicate that the so-called drifting problem upon generic–generic substitution does not result in important differences in exposure upon exchanging topiramate generics or gabapentin generics.
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Acknowledgements
All authors, except Nikola Banishki, are appointed to the Dutch Medicines Evaluation Board (MEB-CBG). Nikola Banishki has been working as a student at this Agency. All authors had access to the application dossiers filed at the Regulatory Agency. The opinions of the authors expressed in this paper do not necessarily reflect those of the Dutch Medicines Evaluation Board MEB-CBG.
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Maliepaard, M., Banishki, N., Gispen-de Wied, C.C. et al. Interchangeability of generic anti-epileptic drugs: a quantitative analysis of topiramate and gabapentin. Eur J Clin Pharmacol 67, 1007–1016 (2011). https://doi.org/10.1007/s00228-011-1041-4
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DOI: https://doi.org/10.1007/s00228-011-1041-4