Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia

• Published in: British journal of clinical pharmacology Vol. 85; no. 9; pp. 2059 - 2065
• Main Authors: Pejčić, Zorica, Vučićević, Katarina, García‐Arieta, Alfredo, Miljković, Branislava
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01-09-2019
• Subjects: Area Under Curve; bioequivalence; Biological Availability; Clopidogrel - pharmacokinetics; Drugs, Generic - pharmacokinetics; generic–generic substitution; Humans; interchangeability; Original; Platelet Aggregation Inhibitors - pharmacokinetics; Serbia; switchability; therapeutic equivalence; Therapeutic Equivalency; Serbia; interchangeability; switchability; therapeutic equivalence; generic-generic substitution; bioequivalence
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.13997

Aims
Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by means of adjusted indirect comparisons (AICs).
Methods
AICs were conducted to assess bioequivalence between 4 generic clopidogrel products that are authorised in Serbia. Generics are considered equivalent to the reference if the 90% confidence intervals (CIs) for the ratios test/reference of the maximum concentration (Cmax) and area under the curve up to the last measurable concentration (AUC0–t) fall within the acceptance range 80.00–125.00%. However, for AICs between generics, the Canadian acceptance criterion for Cmax was employed, where only the point estimate of Cmax needs to be within 80.00–125.00%.
Results
The 90% CIs of the AICs demonstrated bioequivalence within 80.00–125.00% for all AUC0–t comparisons. The point estimates of Cmax in all AICs were also within this range.
Conclusion
This study demonstrates that the bioavailability of these 4 generic clopidogrel products authorised in Serbia is very similar. Despite the limited power of AICs, bioequivalence was demonstrated for all 90% CIs of AUC0–t and all 90% CIs of Cmax comparisons were within or very close to the acceptance range, being able to comply with the acceptance criterion employed in Canada for Cmax. Therefore, these 4 generic clopidogrel products authorised in Serbia can be considered switchable with each other in clinical practice based on the adjusted indirect comparisons.