Amoxicillin/Clavulanate-Associated Hepatic Failure with Progression to Stevens–Johnson Syndrome

Limauro, David L.; Chan-Tompkins, Noreen H.; Carter, Russell W; Brodmerkel, G.J.; Agrawal, Rad

doi:10.1345/aph.18104

Cited by 22 publications

(6 citation statements)

References 22 publications

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“…Results of ROR analysis confirmed this disproportionality for amoxicillin/clavulanic acid-related SJS, although a search through the literature did not reveal other comparative studies on this specific issue, but only some published case reports. 28,29 In line with the literature, 3,4 it was found that amoxicillin/clavulanic acid is associated with a higher number of reports of gastrointestinal reactions, although these are less serious (12% versus 21%). Two clinical trials found that the frequency of gastrointestinal events is related to the dosage of clavulanic acid.…”

Section: Discussionsupporting

confidence: 58%

Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy

Salvo

Polimeni

Moretti

et al. 2007

Journal of Antimicrobial Chemotherapy

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Objectives: To analyse an Italian database of spontaneous reporting of suspected adverse drug reactions in order to compare the safety profile of amoxicillin and amoxicillin/clavulanic acid.Methods: Data were retrieved from the spontaneous reports collected by six Italian regions (the GIF database) from January 1988 to June 2005. Drug utilization data were also available for the two drugs. The comparison between amoxicillin and amoxicillin/clavulanic acid was made using the x 2 or Student's t-test, when appropriate. Disproportionality in reporting of adverse events was assessed using reporting odds ratio methodology.Results: Up to June 2005, the GIF database collected 37 906 reports, of which 1088 were related to amoxicillin/clavulanic acid and 1095 to amoxicillin. The percentage of skin reactions was statistically higher for amoxicillin (82%) than for amoxicillin/clavulanic acid (76%); on the contrary, the percentage of gastrointestinal, hepatic and haematological reactions was significantly higher for amoxicillin/ clavulanic acid (13%, 4% and 2%, respectively) than for amoxicillin (7%, 1% and 1%, respectively). Amoxicillin/clavulanic acid seems to be associated with a higher risk of Stevens-Johnson syndrome, purpura and hepatitis than amoxicillin alone. In particular, the reporting rate of hepatitis is on average 9-fold higher for amoxicillin/clavulanic acid than for amoxicillin.Conclusions: Analysis shows a different safety profile for the two selected drugs. The combination of amoxicillin/clavulanic acid has been increasingly used in Italy and now represents the most frequently antibiotic prescribed by Italian general practitioners. Given the documented level of inappropriate use of b-lactams in Italy, these results should be taken into account by physicians before prescribing amoxicillin/clavulanic acid to patients.

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Section: Discussionsupporting

confidence: 58%

Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy

Salvo

Polimeni

Moretti

et al. 2007

Journal of Antimicrobial Chemotherapy

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“…Several of the patients had prominent extrahepatic manifestations such as Steven's Johnson Syndrome, interstitial nephritis, and thrombotic thrombocytopenic purpura emphasizing the complex, systemic nature of some of these severe drug reactions (16,18,22). In 1996, the Australian Adverse Drug Reactions Advisory Committee (ADRAC) reported nine Australian patients with amoxicillin/clavulanate hepatotoxicity that had died (21).…”

Section: Discussionmentioning

confidence: 99%

Acute Liver Failure Due To Amoxicillin and Amoxicillin/Clavulanate

et al. 2005

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The aim of our study is to report upon the presentation of two patients with life-threatening acute liver failure (ALF) due to amoxicillin and amoxicillin/clavulanate. A 59-year-old, Caucasian male presented with ALF 34 days after receiving amoxicillin/clavulanate. Despite aggressive supportive care, he died on hospital day 10. A 42-year-old, Caucasian female presented with ALF 21 days after receiving amoxicillin. She underwent successful liver transplantation on hospital day 19. In both cases, all competing causes of ALF had been excluded, liver pathology was consistent with drug-induced hepatitis, and cases were deemed "definite/highly probable" using causality assessment. Amongst 14 prior ALF/death cases due to amoxicillin/clavulanate, the mean age (62 years), male predominance (57%), and mean delay from drug cessation to presentation (17 days) is similar to what has been reported in patients with self-limited cholestatic hepatitis. Acute liver failure is a rare manifestation of amoxicillin and amoxicillin/clavulanate hepatotoxicity with no obvious clinical features at presentation portending a poor prognosis. Early transfer of patients with severe drug-induced hepatotoxicity (i.e., encephalopathy or coagulopathy) to a transplant center is recommended due to their poor likelihood of recovery.

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“…Histologically, a spectrum of cholestatic liver injury can occur that includes pure intrahepatic cholestasis, and mixed hepatitic/cholestatic injury, which, occasionally, may evolve into vanishing bile duct syndrome [7, 8]. Jaundice is typical of patients with AC-DILI reported in the literature; most recover fully, although death or need for liver transplant may occur [9, 10]. The US DILIN cohort, established in 2004, now consists of over 1450 cases of DILI, of which 11 % are due to AC.…”

Section: Introductionmentioning

confidence: 99%

Amoxicillin–Clavulanate-Induced Liver Injury

et al. 2016

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Background and Aims Amoxicillin–clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs. Methods Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. Results One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. Conclusion AC-DILI causes a moderately severe, mixed hepatocellular–cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation.

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Amoxicillin/Clavulanate-Associated Hepatic Failure with Progression to Stevens–Johnson Syndrome

Cited by 22 publications

References 22 publications

Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy

Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy

Acute Liver Failure Due To Amoxicillin and Amoxicillin/Clavulanate

Amoxicillin–Clavulanate-Induced Liver Injury

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