title: Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity: a prospective series from Spain.
abstract: Amoxicillin-clavulanate (AC) hepatotoxicity has been reported to exhibit a higher predominance of cholestatic types of damage, especially in males. However, the determinants of its clinical expression are unknown. This study prospectively evaluated the profile of AC hepatotoxicity. Data on all cases of hepatotoxicity reported to the Spanish Registry attributed to AC and assessed as definite or probable on the Council for International Organizations of Medical Sciences (CIOMS) scale were collated and compared to published case series. Hepatotoxicity related to amoxicillin-clavulanate was identified in 69 patients (36 males; mean age 56 years) representing 14% of all cases of hepatotoxicity submitted to the Registry. There was an overall sex distribution and the predominant pattern of lesion was hepatocellular (36%) which occurred at a shorter duration of treatment (P < .03). Mean time lapse between therapy initiation and jaundice onset was 16 days. Late onset of symptoms following end of treatment occurred in half the cases. Multiple logistic regression analysis identified advancing age as the factor associated with the development of cholestatic/mixed type of injury (odds ratio for an age interval for 1 year: 1.045 [95% CI = 1.013-1.078; P = .005). An unfavorable outcome was seen in 7% of patients. In conclusion, age is the most important determinant in the biochemical expression of AC hepatotoxicity; younger age is associated with cytolytic damage and shorter treatment duration, whereas cholestatic/mixed type of damage is related to older age and prolonged AC therapy.
authors.affiliation: Servicio de Farmacología Clínica, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Coordinating Centre, Hospital Universitario Virgen de la Victoria, Málaga, Spain. lucena@uma.es
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Fernández
authors.forename: Ketevan
authors.initials: K
authors.lastname: Pachkoria
authors.forename: Gloria
authors.initials: G
authors.lastname: Pelaez
authors.forename: José A
authors.initials: JA
authors.lastname: Durán
authors.forename: Macarena
authors.initials: M
authors.lastname: Villar
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.forename: Ramón
authors.initials: R
authors.lastname: Planas
authors.forename: Anabel
authors.initials: A
authors.lastname: Barriocanal
authors.forename: Joan
authors.initials: J
authors.lastname: Costa
authors.forename: Carlos
authors.initials: C
authors.lastname: Guarner
authors.forename: Sonia
authors.initials: S
authors.lastname: Blanco
authors.forename: José M
authors.initials: JM
authors.lastname: Navarro
authors.forename: Fernando
authors.initials: F
authors.lastname: Pons
authors.forename: Agustin
authors.initials: A
authors.lastname: Castiella
authors.forename: Susana
authors.initials: S
authors.lastname: Avila
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury; D004342:Drug Hypersensitivity; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008107:Liver Diseases / Q000453:epidemiology / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013030:Spain / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents; D019980:Amoxicillin-Potassium Clavulanate Combination