Quality of amoxicillin/clavulanic acid oral formulations for intended veterinary use in the UK, Malaysia, Serbia and Thailand.
Journal
The Journal of small animal practice
ISSN: 1748-5827
Titre abrégé: J Small Anim Pract
Pays: England
ID NLM: 0165053
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
27
02
2023
received:
07
12
2022
accepted:
24
05
2023
medline:
23
10
2023
pubmed:
21
6
2023
entrez:
21
6
2023
Statut:
ppublish
Résumé
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. 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). 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. 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.
Substances chimiques
Amoxicillin-Potassium Clavulanate Combination
74469-00-4
Amoxicillin
804826J2HU
Clavulanic Acid
23521W1S24
Tablets
0
Anti-Infective Agents
0
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
626-634Informations de copyright
© 2023 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.
Références
European Medicines Agency (2019) 20 years of sampling and testing of centrally Authorised products 1998-2017, https://www.ema.europa.eu/en/documents/report/20-years-sampling-testing-centrally-authorised-products-1998-2017_en.pdf. Accessed November 5, 2022
Gberindyer, F. A., Olaogun, C. S., Adedokun, M. A., et al. (2019) Evaluation of amoxicillin content in commonly used multisource injectable brands in veterinary practice. Egyptian Journal of Veterinary Sciences 50, 159-165. https://doi.org/10.21608/ejvs.2019.13433.1082
Khan, M. H., Hatanaka, K., Sovannarith, T., et al. (2013) Effects of packaging and storage conditions on the quality of amoxicillin-clavulanic acid - an analysis of Cambodian samples. BMC Pharmacology & Toxicology 14, 33. https://doi.org/10.1186/2050-6511-14-33
Lemeshow, S. & Taber, S. (1991) Lot quality assurance sampling: single- and double-sampling plans/Stanley Lemeshow & Scott Taber. World Health Statistics Quarterly 44, 115-132
Newton, P. N., Lee, S. J., Goodman, C., et al. (2009) Guidelines for field surveys of the quality of medicines: a proposal. PLoS Medicine 6, e52. https://doi.org/10.1371/journal.pmed.1000052
Official Medicines Control Laboratories (2022) OMCL - Background and mission. https://www.edqm.eu/en/omcl-background-and-mission. Accessed September 30, 2022
Pellicaan, C. H., Hilarius, D. L., Mesu, S. J., et al. (1996) Farmaceutische kwaliteit van amoxicilline bevattende tabletten voor veterinair gebruik. Tijdschrift voor Diergeneeskunde 1, 126-130
Seifu, A., Kebede, E., Bacha, B., et al. (2019) 'Quality of albendazole tablets legally circulating in the pharmaceutical market of Addis Ababa, Ethiopia: physicochemical evaluation. BMC Pharmacology and Toxicology 20, 20. https://doi.org/10.1186/s40360-019-0299-5
Steagall, P. V., Pelligand, L., Page, S. W., et al. (2020) The world small animal veterinary association (WSAVA). Journal of Small Animal Practice 61, E162-E176. https://doi.org/10.1111/jsap.13135
Thambavita, D., Galappatthy, P., Mannapperuma, U., et al. (2017) Biowaiver monograph for immediate-release solid oral dosage forms: amoxicillin trihydrate. Journal of Pharmaceutical Sciences 106, 2930-2945. https://doi.org/10.1016/j.xphs.2017.04.068
United States Pharmacopeia (2009) Amoxicillin and clavulanate potassium tablets. https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisions/amoxicillinClavulanateTablets.pdf. Accessed November 5, 2022
Vidhamaly, V., Bellingham, K., Newton, P. N., et al. (2022) 'The quality of veterinary medicines and their implications for one health. BMJ Globalization and Health 7, e008564. https://doi.org/10.1136/bmjgh-2022-008564
World Health Organization (2018) Medical product alert N°2/2018 falsified “Augmentin” circulating in Cameroon. http://fdd.gov.la/download/documents/2018-03-05_043352pm_n2.2018%20WHO%20alert_Falsified%20%20augmentin.pdf. Accessed November 5, 2022
World Health Organization (2019a) Medical product alert N° 9/2019: falsified augmentin found in Uganda and Kenya. https://www.who.int/news/item/20-08-2019-medical-product-alert-n-9-2019-(english-version). Accessed November 5, 2022
World Health Organization (2019b) Medical product alert N° 11/2019 falsified amoxicillin + clavulanic acid products circulating in Haiti. https://www.who.int/news/item/18-10-2019-medical-product-alert-n-11-2019-(english-version). Accessed November 5, 2022
World Health Organization (2020) A study on the public health and socioeconomic impact of substandard and falsified medical products. https://www.who.int/publications/i/item/9789241513432. Accessed December 1, 2022
World Health Organization (2021) Model List of Essential Medicines-22nd List. https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.02. Accessed November 5, 2022
World Health Organization (2022) Substandard and falsified medical products. https://www.who.int/health-topics/substandard-and-falsified-medical-products#tab=tab_1. Accessed November 5, 2022
WSAVA TGG (2020) WSAVA list of essential medicines for cats and dogs. https://wsava.org/news/highlighted-news/wsava-list-of-essential-medicines-for-cats-and-dogs/. Accessed April 21, 2020
Zabala, G. A., Bellingham, K., Vidhamaly, V., et al. (2022) Substandard and falsified antibiotics: neglected drivers of antimicrobial resistance? BMJ Globalization and Health 7, e008587. https://doi.org/10.1136/bmjgh-2022-008587