amoxicillin-potassium-clavulanate-combination and Liver-Failure

There is a growing body of evidence that amoxicillin-clavulanic acid may induce severe adverse effects in patients.. A medline search of case reports and reviews on amoxicillin-clavulanic acid induced adverse effects was performed. The criteria of a consensus conference on the reporting of drug-induced liver disease were applied.. Amoxicillin-clavulanic acid has been associated with drug-induced cholestatic hepatitis in 208 reported patients. In 153 evaluable patients there were 106 males and 47 females with a mean age of 60 years (1-90). Liver associated co-morbidity and co-medication does not play a major part in the development of disease. In most instances respiratory tract infection and sinusitis were treated by amoxicillin-clavulanic acid with a mean treatment duration of 13.9 days and a reaction time until first onset of jaundice of 25.2 days average. Infection and cholestasis from other reason were ruled out in most patients. Liver injury was classified according to laboratory parameters to be hepatocellular in 35 patients, cholestatic in 24 patients and mixed in 83 patients. Normalization of liver enzymes was observed 11.5 weeks after onset of drug administration (average); three of 153 patients did not survive the adverse event.. Amoxicillin-clavulanic acid which is marketed for treatment of respiratory infections and sinusitis/otitis may in some cases induce severe adverse effects and death in patients of different age, especially if they are on multidrug regimens. In consideration of this fact many authors recommend to reflect carefully, whether amoxicillin-clavulanic acid is necessary in treatment of patients with localized or uncomplicated infections. If amoxicillin-clavulanic acid is prescribed, transaminase, alkaline phosphatase and bilirubin tests should be obtained within the first two weeks and after four to five weeks after beginning of treatment to recognize early enough undesired hepatic side effects.

Topics: Adolescent; Adult; Age Distribution; Americas; Amoxicillin-Potassium Clavulanate Combination; Asia; Australia; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholestasis; Comorbidity; Europe; Female; Humans; Infant; Liver Diseases; Liver Failure; Male; Middle Aged; Respiratory Tract Infections; Retrospective Studies; Sex Distribution

Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases.. A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed.. Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001).. Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Analysis of Variance; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Incidence; Liver; Liver Diseases; Liver Failure; Male; Middle Aged; Odds Ratio; Probability; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Sex Distribution; Spain; Survival Analysis

To describe a patient who developed hepatic failure, Stevens-Johnson syndrome (SJS), and died after receiving amoxicillin/clavulanate therapy.. A 37-year-old white man without significant past medical history received a 10-day course of amoxicillin/clavulanate for treatment of pneumonia. Thirty-two days after starting amoxicillin/clavulanate, he developed jaundice, rash, pruritus, and increasing fatigue. On further evaluation, with the exclusion of toxicity from other drugs or diseases, the time course to development of cholestatic jaundice correlated with the use of amoxicillin/clavulanate. The patient consequently died with progressive hepatic failure, renal failure, and SJS.. Hepatic injury has been reported with amoxicillin/clavulanate. Signs and symptoms of jaundice and pruritus may appear up to to six weeks after stopping therapy. Most cases of liver injury have been benign and reversible on discontinuation of the amoxicillin/clavulanate. Reported hepatic reactions have been mainly cholestatic, with some mixed cholestatic/hepatocellular liver function test abnormalities.. Clinicians should be aware of amoxicillin/clavulanate as a drug capable of causing hepatitis with eventual systemic dysfunction. While recovery is usually complete following withdrawal of the drug, in patients with rash associated with hepatic dysfunction, renal insufficiency, or other unusual symptoms, earlier consideration of initiating systemic steroids or liver transplantation referral, in hopes of avoiding progressive systemic response, might be worthwhile.

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Blood Chemical Analysis; Drug Therapy, Combination; Fatal Outcome; Humans; Liver Failure; Male; Pneumonia; Renal Insufficiency; Stevens-Johnson Syndrome