Investigation into the interchangeability of generic formulations using immunosuppressants and a broad selection of medicines

PURPOSE: To date, the interchangeability of generic drugs has only been investigated for a limited number of medicines. The objective of this study was to investigate generic-generic drug interchangeability in a large subset of generic formulations in order to cover a broad spectrum of drugs. METHODS: Orally administered drugs for investigation in this study were selected using strict, predefined criteria, with the purpose to avoid bias. This selection procedure yielded atorvastatin, bicalutamide, naratriptan, olanzapine, perindopril, and venlafaxine. Further, ciclosporin, tacrolimus, and mycophenolate mofetil were investigated as test immunosuppressants. Adjusted indirect comparisons were conducted between generic drugs containing the same active substance, and the 90 % confidence interval (CI) for AUC and C(max) was calculated. RESULTS: In total, 120 bioequivalence studies were identified in the Dutch medicine regulatory agency’s database, allowing 292 indirect comparisons between generic drugs. The indirect comparison results indicated that in the vast majority of cases, i.e., 80.5 %, the 90 % CIs for both AUC(t) and C(max) fell within the bioequivalence criteria (in 90.1 and 87.0 % for AUC(t) and C(max), respectively). In 1 % of the 292 indirect comparison for AUC(t) and 3 % for C(max), a wider range of 75–133 % (or 80–125 %) was exceeded. CONCLUSIONS: Overall, our study suggests that exposure-related risks associated with the exchange of different generic drugs in clinical practice are not increased to a relevant extent compared to the situation in which a generic is exchanged with the innovator. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00228-015-1878-z) contains supplementary material, which is available to authorized users.