Risk factors for severe or fatal drug‐induced liver injury from amoxicillin–clavulanic acid

Yazıcı, Cemal; Mutlu, Ece; Bonkovsky, Herbert L.; Russo, Mark W.

doi:10.1111/hepr.12410

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…Another alternative for CA studies is antibiotic side effects. For instance, despite the effectiveness of amoxicillin/CA in the treatment against pathogenic bacteria with resistance to β-lactam antibiotics, it is also considered one of the most frequently associated drugs with drug injury; however, further studies are required to analyze drug integration between amoxicillin/CA and concomitant potential hepatotoxic drugs [23,24,25]. Additionally, some drug eruption to CA has been reported, e.g., a patient developed a drug eruption on the day following amoxicillin and CA administration, which was considered a delayed hypersensitivity reaction [26].…”

Section: Resultsmentioning

confidence: 99%

Bibliometric Analysis of Global Research on Clavulanic Acid

Ramírez-Malule

2018

Antibiotics

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Clavulanic acid (CA), a potent inhibitor of the β-lactam, ase enzyme, is frequently co-formulated with a broad spectrum of antibiotics to treat infections caused by β-lactamase-producing pathogens. In order to evaluate the impact and the progress of CA studies in the last four decades, a bibliometric analysis of the global scientific production of CA was carried out. A total of 39,758 records in the field of CA were indexed in the Scopus database for a 43-year period of study (1975–2017). The results indicated that CA studies have grown, showing three phases (1975–1999, 2000–2003 and 2004–2017) based on records of publications; the results showed a sigmoidal profile. Medicine was the main subject area for CA studies, whereas biochemistry, genetics and molecular biology were areas of research for CA production by Streptomyces clavuligerus (S. clavuligerus). Nevertheless, chemical engineering (as a subject area) had the highest increase in the percentage of publications related to CA production by S. clavuligerus. The United States, France, the United Kingdom, Spain and Brazil were the leading countries in the scientific production of studies on both CA and CA related to S. clavuligerus. This analysis allowed the identification of the area of knowledge with the highest impact on CA studies, the top researchers and their geographic distribution, and also helped to highlight the existence of antibiotic-resistant bacteria as an emergent area in CA research.

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Section: Resultsmentioning

confidence: 99%

Bibliometric Analysis of Global Research on Clavulanic Acid

Ramírez-Malule

2018

Antibiotics

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“…Similarly, a systematic review reported an increased risk of severe or fatal hepatotoxicity when amoxicillin: clavulanate is coadministered with drugs associated with hepatotoxicity, including antimicrobials, analgesics and hormonal therapy (Yazici et al, 2014). Examining clinical factors and preclinical mechanisms, most (67%) drugs withdrawn from the market or displaying black box warnings for drug-induced liver injury exhibit inhibition of both liver mitochondrial and bile salt export pump function (Aleo et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Comedications alter drug-induced liver injury reporting frequency: Data mining in the WHO VigiBase™

Suzuki

Yuen

Ilic³

et al. 2015

Regulatory Toxicology and Pharmacology

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Polypharmacy is common, and may modify mechanisms of drug-induced liver injury. We examined the effect of these drug–drug interactions on liver safety reports of four drugs highly associated with hepatotoxicity. In the WHO VigiBase™, liver event reports were examined for acetaminophen, isoniazid, valproic acid, and amoxicillin/clavulanic acid. Then, we evaluated the liver event reporting frequency of these 4 drugs in the presence of co-reported medications. Each of the 4 primary drugs was reported as having more than 2000 liver events, and co-reported with more than 600 different medications. Overall, the effect of 2275 co-reported drugs (316 drug classes) on the reporting frequency was analyzed. Decreased liver event reporting frequency was associated with 245 drugs/122 drug classes, including anti-TNFα, opioids, and folic acid. Increased liver event reporting frequency was associated with 170 drugs/82 drug classes; in particular, halogenated hydrocarbons, carboxamides, and bile acid sequestrants. After adjusting for age, gender, and other co-reported drug classes, multiple co-reported drug classes were significantly associated with decreased/increased liver event reporting frequency in a drug-specific/unspecific manner. In conclusion, co-reported medications were associated with changes in the liver event reporting frequency of drugs commonly associated with hepatotoxicity, suggesting that comedications may modify drug hepatic safety.

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“…According to Yazici et al [27], the risk of death among users of co-amoxiclav increases with the use of concomitant hepatotoxic medications and they suggest that these patients may have concomitant diseases with less ability to recover from a severe DILI compared to healthier patients, or even that the occurrence of drug- drug interactions between amoxiclav and other hepatotoxic agents may result in a more serious liver injury. In their recent paper Suzuki et al [28] analyzed the reporting frequency of liver events of four drugs (one of them was co-amoxiclav) in the presence of co-reported medications on the basis of the WHO global individual case safety report database (VigiBase™); they showed that co-reported drugs were associated with changes in the frequency of hepatic ADR reporting of drugs usually associated with hepatotoxicity, suggesting that co-medications could modify drug hepatic safety.…”

Section: Discussionmentioning

confidence: 99%

Liver Injury due to Amoxicillin vs. Amoxicillin/Clavulanate: A Subgroup Analysis of a Drug-Induced Liver Injury Case-Control Study in Italy

Donati¹,

Motola²,

Leone³

et al. 2017

J Hepatol Gastroint Dis

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Objective: Several studies showed that amoxicillin plus clavulanic acid (co-amoxiclav) is one of the most common agents associated to serious Drug Induced Liver Injury (DILI). We estimated the risk of acute serious DILI associated with amoxicillin alone compared with co-amoxiclav, through a multicenter case-control study carried out in nine Italian hospitals from October 2010 to January 2014. Methods:Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders, not related to chronic conditions and not involving the liver. Adjusted Odds Ratio (ORs) with 95% CI were calculated initially with a bivariate and then multivariate analysis. Results:We analysed 179 cases matched to 1770 controls. Seven cases were exposed to amoxicillin (adjusted OR 1.69, 95% CI 0.72-3.98) and 22 cases to co-amoxiclav (adjusted OR 3.00, 95% CI 1.76-5.40). Conclusions:Co-amoxiclav almost doubled the risk of serious acute liver injury compared to amoxicillin alone. The incidence of co-amoxiclav induced DILI is very low but the widespread use of this drug by the general population makes the risk clinically relevant. The often inappropriate prescription of antimicrobial agents, and in particular of co-amoxiclav, could expose a given patient to a life-threatening risk compared to a negligible clinical benefit.

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Risk factors for severe or fatal drug‐induced liver injury from amoxicillin–clavulanic acid

Cited by 7 publications

References 28 publications

Bibliometric Analysis of Global Research on Clavulanic Acid

Bibliometric Analysis of Global Research on Clavulanic Acid

Comedications alter drug-induced liver injury reporting frequency: Data mining in the WHO VigiBase™

Liver Injury due to Amoxicillin vs. Amoxicillin/Clavulanate: A Subgroup Analysis of a Drug-Induced Liver Injury Case-Control Study in Italy

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