Quality of amoxicillin/clavulanic acid oral formulations for intended veterinary use in the UK, Malaysia, Serbia and Thailand

Pelligand L 1 , Baker D 2 , Sivagurunathan A 3 , Kovačević Z 4 , Suemanotham N 5 , Stair JL 2 Show all authors , Scott M 2 , Liu F 2 , Page SW 6 , Guardabassi L 7 , Steagall PV 8 , Therapeutic Guidelines Group of the World Small Animal Veterinary Association

Affiliations 

  • 1 Department of Clinical Services and Sciences and Department of Comparative Biomedical Sciences, Royal Veterinary College, Hatfield, UK
  • 2 Department of Clinical, Pharmaceutical & Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
  • 3 Animal Medical Centre, Kuala Lumpur, Malaysia
  • 4 Department for Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia
  • 5 Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand
  • 6 Veterinary Clinical Pharmacology and Toxicology, Advanced Veterinary Therapeutics, Newtown, NSW, 2042, Australia
  • 7 Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
  • 8 Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, QC, J2S 2M2, Canada
J Small Anim Pract, 2023 Oct;64(10):626-634.
PMID: 37340896 DOI: 10.1111/jsap.13648

Abstract

OBJECTIVES: Amoxicillin/clavulanate 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 amoxicillin/clavulanate in various countries.

MATERIALS AND METHODS: In a prospective study with purposive sampling, amoxicillin/clavulanate tablet formulations for canine use were collected in four countries (wholesalers or veterinary practice) and shipped to a central bioanalytical laboratory. Twenty-four samples were collected from the UK (nine), Malaysia (nine), Serbia (four) and Thailand (two), yielding 18 different formulations (10 veterinary). Packaging inspection, tablet disintegration and content assay were conducted (validated high-performance liquid chromatography with ultra-violet detection); content was acceptable when within the 90% to 120% pre-specified range (US Pharmacopeia).

RESULTS: Secondary packaging was present for 13 of 24 samples and primary packaging integrity was verified for all but one sample. Amoxicillin trihydrate/potassium clavulanate label ratio was 4:1, except for three formulations (2:1). Tablet dose strength ranged from 250 to 625 mg. All formulations contained both analytes. For amoxicillin, two of 24 samples were out of specification with 72.8% (Malaysia) and 82.3% (Thailand) of labelled content. For clavulanate, four of 24 samples were out of specification 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: Antimicrobial formulations of substandard quality have negative consequences for efficacy in patients and potentially promote antimicrobial resistance. 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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