American Journal of Pharmacological Sciences
ISSN (Print): 2327-6711 ISSN (Online): 2327-672X Website: Editor-in-chief: Srinivas NAMMI
Open Access
Journal Browser
American Journal of Pharmacological Sciences. 2017, 5(1), 8-10
DOI: 10.12691/ajps-5-1-2
Open AccessArticle

The Action of Amoxicillin-Clavulanate on Hepatocytes

Omar Rashid Sadeq1,

1Faculty of Dentistry, Arab American University, Jenin., (AAUJ), Palestine, P.O Box 240 Jenin, 13 Zababdeh

Pub. Date: March 04, 2017

Cite this paper:
Omar Rashid Sadeq. The Action of Amoxicillin-Clavulanate on Hepatocytes. American Journal of Pharmacological Sciences. 2017; 5(1):8-10. doi: 10.12691/ajps-5-1-2


The oral antibiotic amoxicillin is third generation penicillin combined to clavulanate, widely employed in medicine and dentistry for treatment of mild-to-moderate bacterial infections. Clavulanate is not indicated alone because it lacks antibacterial activity, so it is added to amoxicillin in order to inactivate beta-lactamse enzyme which is the major cause of penicillin resistance. Beta- lactamase is produced by many microorganisms, it destroys beta lactam ring of beta lactam antibiotics, therefore amoxicillin-clavulante is indicated as an extended antibiotic that covers many gram positive a and a significant number of gram negative microorganisms which produce beta-lactamse. This compound amoxicillin-clavulanate is available in multiple dose variations, typically as 250, 500 to 875 mg amoxicillin with 125 mg of clavulanate potassium, given two to three times daily for 7 to 10 days. The combination is provided in many trade formulation namely moclav and agumentin. Amoxicillin is in general use because it is the most effective and least toxic antibiotic, however it can cause some unwanted effects particularly allergic, GIT and renal effects. The purpose of recent study is to estimate possibility toxic effect of amoxicillin-clavulanate on hepatocytesand its revesibility, about 64 infectious patients of several ages were investigated, 35 of them are men and the 29 are women, for about 3 weeks. Complete blood count (CBC) and serum of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and gamma glutamyltranspeptidase (gamma-GT) are taken before, and after completion of treatment. The main finding of this research is that amoxicillin-clavulanate has a toxic effect on hepatocytes, represented mainly by reversible cholestatic hepatitis in patients older 50 years, who experience fatigue, GIT upset, prurituts and jaundice. The hepatic injury has occurred in elderly men more than in women.

amoxicillin clavulanate beta-lactamase moclav agumentin alkaline phosphatase gamma glutamyltranspeptidase alanine transaminase aspartate transaminase prurituts jaundice

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  DeLemos AS, Ghabril M, Rockey DC, Gu J, Barnhart HX, Fontana RJ, Kleiner DE, et al; Drug-Induced Liver Injury Network (DILIN). Amoxicillin-clavulanate-induced liver injury. Dig Dis Sci. 2016 Mar 22.
[2]  Björnsson ES. Hepatotoxicity by Drugs: The Most Common Implicated Agents. Int J MolSci 2016; 17.
[3]  Ferrer P, Amelio J, Ballarín E, Sabaté M, Vidal X, Rottenkolber M, Schmiedl S, et al; PROTECT Work Package 2.. Systematic Review and Meta-Analysis: Macrolides and Amoxicillin/Clavulanate-induced Acute Liver Injury. Basic ClinPharmacolToxicol 2015 Dec 26.
[4]  Moreno L, Sánchez Delgado J, Vergara M, Casas M, Miquel M, Dalmau B. Recurrent drug-induced liver injury (DILI) with ciprofloxacin and amoxicillin/clavulanic. Rev EspEnferm Dig. 2015 Dec; 107: 767-8.
[5]  Kim SH, Saide K, Farrell J, Faulkner L, Tailor A, Ogese M, Daly AK, et al. Characterization of amoxicillin- and clavulanic acid-specific T cells in patients with amoxicillin-clavulanate-induced liver injury. Hepatology 2015; 62: 887-99.
[6]  Mengual-Moreno E, Lizarzábal-García M, Ruiz-Soler M, Silva-Suarez N, Andrade-Bellido R, Lucena-González M, Bessone F, et al. [Case reports of drug-induced liver injury in a reference hospital of Zulia state, Venezuela]. Invest Clin 2015; 56: 3-12. Spanish.
[7]  Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-1352.e7.
[8]  Björnsson ES. Drug-induced liver injury: an overview over the most critical compounds. Arch Toxicol 2015; 89: 327-34.
[9]  Fontana RJ. Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives. Gastroenterology 2014; 146: 914-28.
[10]  Devarbhavi H, Andrade RJ. Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs. Semin Liver Dis. 2014; 34: 145-61.
[11]  Romero-Gómez M, Moreno-Casares A, et al. HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity. PLoS One 2013; 8: e68111.
[12]  Moseley RH. Hepatotoxicity of antimicrobials and antifungal agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 463-82.
[13]  Sistanizad M, Peterson GM. Drug-induced liver injury in the Australian setting. J Clin Pharm Ther 2013; 38: 115-20.
[14]  Beraldo DO, Melo JF, Bonfim AV, Teixeira AA, Teixeira RA, Duarte AL. Acute cholestatic hepatitis caused by amoxicillin/clavulanate. World J Gastroenterol 2013; 19: 8789-92.
[15]  Sánchez-Ruiz-Granados E, Bejarano-García A, Uceda-Torres E. Recurrent cholestasis by amoxicillin-clavulanic acid: the importance of a correct diagnosis of hepatotoxicity. Rev EspEnferm Dig 2012; 104: 616-7.
[16]  Petri WA Jr. Penicillins, cephalosporins, and other β-lactam antibiotics. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman &Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1477-1504.
[17]  Herrero-Herrero JI, García-Aparicio J. Corticosteroid therapy in a case of severe cholestasic hepatitis associated with amoxicillin-clavulanate. J Med Toxicol 2010; 6: 420-3.
[18]  Domínguez Jiménez JL, Marín Moreno M, Bernal Blanco E, Puente Gutiérrez JJ, GuioteMalpartida S, de la Mata García M. [Acute cholestatic hepatitis induced by amoxicillin-clavulanic acid]. GastroenterolHepatol 2008; 31: 46. Spanish.
[19]  Sabaté M, Ibáñez L, Pérez E, Vidal X, Buti M, Xiol X, Mas A, et al. Risk of acute liver injury associated with the use of drugs: a multicentre population survey. Aliment PharmacolTher 2007; 25:1401-9.
[20]  Cundiff J, Joe S. Amoxicillin-clavulanic acid-induced hepatitis. Am J Otolaryngol 2007; 28: 28-30.
[21]  Fontana RJ, Shakil AO, Greenson JK, Boyd I, Lee WM. Acute liver failure due to amoxicillin and amoxicillin/clavulanate. Dig Dis Sci 2005; 50: 1785-90.
[22]  Martí J. [Cholestatic hepatitis due to amoxicillin-clavulanic acid with positive re-exposure]. EnfermInfeccMicrobiolClin 2003; 21: 322-3. Spanish.
[23]  Thiim M, Friedman LS. Hepatotoxicity of antibiotics and antifungals. Clin Liver Dis 2003 ; 7: 381-99, vi-vii.
[24]  Jordán T, González M, Casado M, Suárez JF, Pulido F, Guerrero E, Esteban J. [Amoxicillin-clavulanic acid induced hepatotoxicity with progression to cirrhosis.] Gastroenterol Hepatol 2002; 25: 240-3. Spanish.
[25]  Sgro C, Clinard F, Ouazir K, et al. Incidence of drug-induced hepatic injuries: A French population-based study. Hepatology. 2002; 36(2):451-455.23. Boyd IW.
[26]  Comment: history of drug-induced hepatitis and risk of amoxicillin/clavulanate-induced hepatotoxicity. Ann Pharmacother 2001; 35: 1677.
[27]  Schey R, Avni Y, Bruck R, Shirin H. History of drug-induced hepatitis and risk of amoxicillin/clavulanate-induced hepatotoxicity. Ann Pharmacother 2001; 35: 1142-3.
[28]  Berg P, Hahn EG. Hepatotoxic reactions induced by beta-lactamase inhibitors. Eur J Med Res 2001; 6: 535-42.
[29]  Soza A, Riquelme F, Alvarez M, Duarte I, Glasinovic JC, Arrese M. [Hepatotoxicity by amoxicillin/clavulanic acid: case report] Rev Med Chil 1999; 127: 1487-91. Spanish.
[30]  Zimmerman, HJ. Hepatotoxicity from drugs in common use. Semin Liver Dis 1990;10: 322-338.