Use of fomepizole (4-methylpyrazole) for acetaminophen poisoning: A scoping review

Pourbagher‐Shahri, Ali Mohammad; Schimmel, Jonathan; Shirazi, Farshad; Nakhaee, Samaneh; Mehrpour, Omid

doi:10.1016/j.toxlet.2021.11.005

Cited by 14 publications

(9 citation statements)

References 79 publications

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“…Acetylcysteine replenishes glutathione that detoxifies the toxic metabolite NAPQI 10,26 . Although it is an effective antidote, it has therapeutic limitations, with less effectiveness in patients who present following a massive overdose, MR overdose, and delayed APAP presentations (>8 hours post‐ingestion) 18,20,25,27 . Fomepizole has been proposed as an adjunct therapy.…”

Section: Discussionmentioning

confidence: 99%

“…It is a CYP2E1 inhibitor, so it can decrease the formation of NAPQI and augment acetylcysteine treatment. However, the evidence for its use is limited to case reports and small series in high‐risk APAP poisonings 27–29 . A crossover study of 5 healthy volunteers receiving fomepizole just prior to a single dose of 80 mg/kg of APAP 30 showed fomepizole led to significantly lower concentrations of the CYP metabolites detected both in serum and urine.…”

Section: Discussionmentioning

confidence: 99%

“… 10 , 26 Although it is an effective antidote, it has therapeutic limitations, with less effectiveness in patients who present following a massive overdose, MR overdose, and delayed APAP presentations (>8 hours post‐ingestion). 18 , 20 , 25 , 27 Fomepizole has been proposed as an adjunct therapy. It is a CYP2E1 inhibitor, so it can decrease the formation of NAPQI and augment acetylcysteine treatment.…”

Section: Discussionmentioning

confidence: 99%

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Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM‐7)

Chiew

Stathakis

Isoardi

et al. 2023

Clin Pharma and Therapeutics

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Acetaminophen (APAP) is commonly taken in overdose and can cause acute liver injury via the toxic metabolite NAPQI formed by cytochrome (CYP) P450 pathway. We aimed to evaluate the concentrations of APAP metabolites on presentation following an acute APAP poisoning and whether these predicted the subsequent onset of hepatotoxicity (peak alanine aminotransferase > 1,000 U/L). The Australian Toxicology Monitoring (ATOM) study is a prospective observational study, recruiting via two poison information centers and four toxicology units. Patients following an acute APAP ingestion presenting < 24 hours post-ingestion were recruited. Initial samples were analyzed for APAP metabolites, those measured were the nontoxic glucuronide (APAP-Glu) and sulfate (APAP-Sul) conjugates and NAPQI (toxic metabolite) conjugates APAP-cysteine (APAP-Cys) and APAPmercapturate (APAP-Mer). The primary outcome was hepatotoxicity. In this study, 200 patients were included, with a median ingested dose of 20 g, 191 received acetylcysteine at median time of 5.8 hours post-ingestion. Twenty-six patients developed hepatotoxicity, one had hepatotoxicity on arrival (excluded from analysis). Those who developed hepatotoxicity had significantly higher total CYP metabolite concentrations: (36.8 μmol/L

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM‐7)

Chiew

Stathakis

Isoardi

et al. 2023

Clin Pharma and Therapeutics

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“…[7] Inhibiting or deleting CYP2E1 has been shown to effectively reduce the production of NAPQI, block ROS production, and alleviate inflammation in APAP-induced mouse models. [11][12][13] Therefore, this approach has the potential to be a useful therapy in treating APAP-induced ALF. 18𝛽-Glycyrrhetinic acid (18𝛽-GA), a in vivo metabolic component of glycyrrhiza acid while is commonly used as a liver protection drug in clinic, is reported to be a potent inhibitor of CYP2E1, [14] indicating that 18𝛽-GA could be a candidate for ALF treatment.…”

Section: Introductionmentioning

confidence: 99%

A Biomimetic Nanoparticle Exerting Protection against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS

Yao

Tang

Dai

et al. 2023

Adv Healthcare Materials

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Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N‐acetyl‐p‐benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N‐acetylcysteine is the Food and Drug Administration‐approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration‐related adverse effects. In this study, a carrier‐free and bilirubin dotted nanoparticle (B/BG@N) is developed, which is formed using bilirubin and 18β‐Glycyrrhetinic acid, and bovine serum albumin (BSA) is then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. The results demonstrate that B/BG@N can effectively reduce the production of NAPQI as well as exhibit antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 signal axis and reducing the production of inflammatory factors. In vivo study shows that B/BG@N can effectively improve the clinical symptom of the mice model. This study suggests that B/BG@N own increases circulation half‐life, improves accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment.

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“…The FDA-approved standard antidote for APAP overdose is N -acetyl cysteine. According to recent findings, fomepizole could be used as an additional antidote for APAP poisoning [ 6 ].…”

mentioning

confidence: 99%

Acetaminophen: A hazard to immunotherapy

Najeebullah

Ali

Naveed

et al. 2022

Annals of Medicine &Amp; Surgery

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Use of fomepizole (4-methylpyrazole) for acetaminophen poisoning: A scoping review

Cited by 14 publications

References 79 publications

Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM‐7)

Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM‐7)

A Biomimetic Nanoparticle Exerting Protection against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS

Acetaminophen: A hazard to immunotherapy

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