BACKGROUND: Amoxicillin-clavulanic acid combination-associated hepatitis and jaundice was first identified in 1988. Numerous case reports and case series have been published since then, but there is no precise estimate of this risk. METHODS: A retrospective cohort study in the United Kingdom to estimate the risk of acute liver injury associated with the combination of amoxicillin and clavulanic acid and compare it with the one of amoxicillin alone. Data were derived from a cohort of 93,433 users of the combination drug amoxicillin-clavulanic acid and 360,333 users of amoxicillin alone who were aged between 10 and 79 years and who were followed up from 1991 through 1992. After reviewing the information on subjects with suspected liver injury that was recorded on computer files, the clinical records of 177 patients from the attending general practitioners were requested. RESULTS: They were 35 cases of idiopathic acute liver injury. None was fatal. There were 14 cases of acute liver injury among users of amoxicillin alone. The type of liver injury was hepatocellular in half the cases. There were 21 cases of acute liver injury among users of amoxicillin and clavulanic acid together. The type of liver injury was cholestatic in three quarters of the cases. The incidence rates and 95% confidence intervals (CIs) of developing acute liver injury associated with the combination of amoxicillin and clavulanic acid and amoxicillin alone were 1.7 (1.1-2.7) and 0.3 (.02-0.5) per 10 000 prescriptions, respectively. The rate ratios and 95% CIs of acute liver injury for amoxicillin and clavulanic acid together compared with amoxicillin alone were 6.3 (3.2-12.7) for all patients and 8.4 (3.6-20.8) for patients presenting with jaundice. Among users of amoxicillin and clavulanic acid together, the risk of developing acute liver injury was more than 3 times greater after a course of 2 or more consecutive prescriptions than after a single course of therapy. The risk also increased with age among users of amoxicillin and clavulanic acid together. The combination of advancing age and repeated prescriptions resulted in a risk of developing acute liver injury greater than 1 per 1000 users of amoxicillin and clavulanic acid together.
BACKGROUND:Amoxicillin-clavulanic acid combination-associated hepatitis and jaundice was first identified in 1988. Numerous case reports and case series have been published since then, but there is no precise estimate of this risk. METHODS: A retrospective cohort study in the United Kingdom to estimate the risk of acute liver injury associated with the combination of amoxicillin and clavulanic acid and compare it with the one of amoxicillin alone. Data were derived from a cohort of 93,433 users of the combination drug amoxicillin-clavulanic acid and 360,333 users of amoxicillin alone who were aged between 10 and 79 years and who were followed up from 1991 through 1992. After reviewing the information on subjects with suspected liver injury that was recorded on computer files, the clinical records of 177 patients from the attending general practitioners were requested. RESULTS: They were 35 cases of idiopathic acute liver injury. None was fatal. There were 14 cases of acute liver injury among users of amoxicillin alone. The type of liver injury was hepatocellular in half the cases. There were 21 cases of acute liver injury among users of amoxicillin and clavulanic acid together. The type of liver injury was cholestatic in three quarters of the cases. The incidence rates and 95% confidence intervals (CIs) of developing acute liver injury associated with the combination of amoxicillin and clavulanic acid and amoxicillin alone were 1.7 (1.1-2.7) and 0.3 (.02-0.5) per 10 000 prescriptions, respectively. The rate ratios and 95% CIs of acute liver injury for amoxicillin and clavulanic acid together compared with amoxicillin alone were 6.3 (3.2-12.7) for all patients and 8.4 (3.6-20.8) for patients presenting with jaundice. Among users of amoxicillin and clavulanic acid together, the risk of developing acute liver injury was more than 3 times greater after a course of 2 or more consecutive prescriptions than after a single course of therapy. The risk also increased with age among users of amoxicillin and clavulanic acid together. The combination of advancing age and repeated prescriptions resulted in a risk of developing acute liver injury greater than 1 per 1000 users of amoxicillin and clavulanic acid together.
Authors: A Ruigómez; R Brauer; L A García Rodríguez; C Huerta; G Requena; M Gil; Francisco de Abajo; G Downey; A Bate; M Feudjo Tepie; M de Groot; R Schlienger; R Reynolds; O Klungel Journal: Eur J Clin Pharmacol Date: 2014-07-29 Impact factor: 2.953
Authors: M Isabel Lucena; Mariam Molokhia; Yufeng Shen; Thomas J Urban; Guruprasad P Aithal; Raúl J Andrade; Christopher P Day; Francisco Ruiz-Cabello; Peter T Donaldson; Camilla Stephens; Munir Pirmohamed; Manuel Romero-Gomez; Jose Maria Navarro; Robert J Fontana; Michael Miller; Max Groome; Emmanuelle Bondon-Guitton; Anita Conforti; Bruno H C Stricker; Alfonso Carvajal; Luisa Ibanez; Qun-Ying Yue; Michel Eichelbaum; Aris Floratos; Itsik Pe'er; Mark J Daly; David B Goldstein; John F Dillon; Matthew R Nelson; Paul B Watkins; Ann K Daly Journal: Gastroenterology Date: 2011-04-12 Impact factor: 22.682
Authors: Carmen Ferrajolo; Katia M C Verhamme; Gianluca Trifirò; Geert W 't Jong; Carlo Giaquinto; Gino Picelli; Alessandro Oteri; Sandra de Bie; Vera E Valkhoff; Martijn J Schuemie; Giampiero Mazzaglia; Claudio Cricelli; Francesco Rossi; Annalisa Capuano; Miriam C J M Sturkenboom Journal: Drug Saf Date: 2013-10 Impact factor: 5.606