Are there substandard amoxicillin/clavulanic acid oral formulations for intended veterinary use in Malaysia, the United Kingdom, Serbia and Thailand? A convenience sampling study

Pelligand, Ludovic; Baker, Dan; Sivagurunathan, A; Kovačević, Z; Suemanotham, N; Stair, J. L; Scott, M; Liu, F; Page, S; Guardabassi, L; Steagall, P. V.

Abstract

Objectives: Antimicrobial formulations of substandard quality have negative consequences for efficacy in patients and potentially promote antimicrobial resistance. Amoxicillin/clavulanate (AMC) is the most commonly used oral antimicrobial drug in companion animals. The objective of the study was to detect types and frequency of deficits in the quality of veterinary oral formulations of AMC in various countries.
Methods: In a prospective study with purposive sampling, AMC tablet formulations for canine use were collected in 4 countries (wholesalers or veterinary practice) and shipped to a central bioanalytical laboratory. Twenty-four samples were collected from Malaysia (9), the United Kingdom (9), Serbia (4) and Thailand (2), yielding 18 different formulations (10 veterinary). Packaging inspection, tablet disintegration and content assay were conducted (validated HPLC-UV); content was acceptable when within the 90-120% pre-specified range (US Pharmacopeia).
Results: Secondary packaging was present for 13/24 samples and primary packaging integrity was verified for all but one samples. Amoxicillin trihydrate/Potassium clavulanate label ratio was 4:1, except for 3 formulations (2:1). Tablet dose strength ranged from 250 to 625 mg. All formulations contained both analytes. For amoxicillin, 2/24 samples were out of specification (OOS) with 72.8% (Malaysia) and 82.3% (Thailand) of labelled content. For clavulanate, 4/24 samples were OOS with 46.9% (Serbia), 79.0% (UK), 84.3% (Serbia) and 86.5% (Thailand) of labelled content. One formulation (Thailand) failed for both analytes.
Clinical significance: There was evidence of substandard formulations in all countries, not only for amoxicillin but especially for clavulanate; this could compromise equitable access to acceptable quality essential veterinary medicines worldwide.

Citation

Pelligand, L., Baker, D., Sivagurunathan, A., Kovačević, Z., Suemanotham, N., Stair, J. L., Scott, M., Liu, F., Page, S., Guardabassi, L., & Steagall, P. V. (in press). Are there substandard amoxicillin/clavulanic acid oral formulations for intended veterinary use in Malaysia, the United Kingdom, Serbia and Thailand? A convenience sampling study. Journal of Small Animal Practice, https://doi.org/10.1111/jsap.13648

• Journal Article Type: Article
• Acceptance Date: May 24, 2023
• Online Publication Date: Jun 21, 2023
• Deposit Date: Dec 16, 2022
• Publicly Available Date: Aug 11, 2023
• Journal: Journal of Small Animal Practice
• Print ISSN: 0022-4510
• Electronic ISSN: 1748-5827
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1111/jsap.13648
• Keywords: Pharmacology; Antimicrobial resistance; Medicine quality; Substandard and falsified; List of Essential Medicines for cats and dogs; Equitable