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Review

What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose?

Pages 686-691 | Received 11 Dec 2017, Accepted 28 Jan 2019, Published online: 19 Feb 2019

Keep up to date with the latest research on this topic with citation updates for this article.

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Michael Chary, Caroline Vizzi & Xavier Jimenez. (2023) Delayed antidotal fomepizole in massive acetaminophen overdose: a case report. Toxicology Communications 7:1.
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Angela L. Chiew & Geoffrey K. Isbister. (2023) Advances in the understanding of acetaminophen toxicity mechanisms: a clinical toxicology perspective. Expert Opinion on Drug Metabolism & Toxicology 0:0, pages 1-16.
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Huseyin Gungor, Mehmet Ekici & Mehmet Burak Ates. (2023) Lipid-lowering, anti-inflammatory, and hepatoprotective effects of isorhamnetin on acetaminophen-induced hepatotoxicity in mice. Drug and Chemical Toxicology 46:3, pages 566-574.
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Slobodan M. Janković. (2022) Acetaminophen toxicity and overdose: current understanding and future directions for NAC dosing regimens. Expert Opinion on Drug Metabolism & Toxicology 18:11, pages 745-753.
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Ari B. Filip, Sarah E. Berg, Michael E. Mullins & Evan S. Schwarz. (2022) Fomepizole as an adjunctive therapy for acetaminophen poisoning: cases reported to the toxicology investigators consortium (ToxIC) database 2015–2020. Clinical Toxicology 60:9, pages 1006-1011.
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Faisal Syed Minhaj, James B. Leonard, Hyunuk Seung, Bruce D. Anderson, Wendy Klein-Schwartz & Joshua D. King. (2022) In vitro analysis of n-acetylcysteine (NAC) interference with the international normalized ratio (INR). Clinical Toxicology 60:4, pages 489-492.
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John W. Downs, Kirk L. Cumpston, Emily K. Kershner, Michelle M. Troendle, S. Rutherfoord Rose & Brandon K. Wills. (2021) Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine. Clinical Toxicology 59:10, pages 932-936.
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Michael E. Mullins, Lauren H. Yeager & William E. Freeman. (2020) Metabolic and mitochondrial treatments for severe paracetamol poisoning: a systematic review. Clinical Toxicology 58:12, pages 1284-1296.
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Yu Kwan Li, Ka Fung Lam, Cheung Lun William Wong & Anselm Wong. (2020) In vitro study of pharmacobezoar formation in simulated acetaminophen overdose. Clinical Toxicology 58:9, pages 900-906.
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Michael E. Mullins, Mary Yu, Lauren O’Grady, Shariq Khan & Evan S. Schwarz. (2020) Adverse reactions in patients treated with the one-bag method of N-acetylcysteine for acetaminophen ingestion. Toxicology Communications 4:1, pages 49-54.
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Articles from other publishers (33)

Céline Konecki, Zoubir Djerada, Brahim Azzouz, Claire Gozalo, Aurélie Fouley, Yoann Cazaubon & Catherine Feliu. (2023) Management of a delayed acetaminophen exposure after massive overdose: A case study. Therapies 78:6, pages 751-754.
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Charles R. Lefèvre, Felipe Le Divenah, Nicolas Collet, Romain Pelletier, Eric Robert, Martine Ropert, Maxime Pawlowski, Thomas Gicquel & Claude Bendavid. (2023) Avoiding falsely low creatinine concentrations measured in patients treated with N-acetylcysteine for acetaminophen intoxication using enzymo-amperometric method – An in vitro and in vivo study. Clinica Chimica Acta 551, pages 117611.
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Ramalingam Gayatri Devi & Devaraj Ezhilarasan. (2023) Concurrent administration of farnesol protects acetaminophen‐induced acute hepatic necrosis in mice. Journal of Biochemical and Molecular Toxicology 37:11.
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Lesley Pepin, Nikolaus Matsler, Andrew Fontes, Kennon Heard, Brian F. Flaherty & Andrew A. Monte. (2023) Fomepizole Therapy for Acetaminophen-Induced Liver Failure in an Infant. Pediatrics 152:4.
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Shumin Sun, Jie Shen, Jianwei Jiang, Fudi Wang & Junxia Min. (2023) Targeting ferroptosis opens new avenues for the development of novel therapeutics. Signal Transduction and Targeted Therapy 8:1.
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Ka Wu, Jingru Qin, Meizhen Liu, Xin Yan & Chao Guo. (2023) Bioinformatics approach and experimental validation reveal the hepatoprotective effect of pachyman against acetaminophen-associated liver injury. Aging 15:17, pages 8800-8811.
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Angela L. Chiew, Geoffrey K. Isbister, Paul Stathakis, Katherine Z. Isoardi, Colin Page, Kirsty Ress, Betty S.H. Chan & Nicholas A. Buckley. (2023) Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose ( ATOM ‐7) . Clinical Pharmacology & Therapeutics 113:6, pages 1304-1314.
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Pei Wang, Hehong Ma, Xiuzhen Hou, Lili Song & Miaoxiao Feng. (2022) N ‐acetyl‐L‐cysteine ameliorates gestational diabetes mellitus by inhibiting oxidative stress . Biotechnology and Applied Biochemistry 70:3, pages 1128-1136.
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Ron Beloosesky, Ola Gutzeit, Yuval Ginsberg, Nizar Khatib, Michael G. Ross, Zeev Weiner & Osnat Zmora. (2023) Intestine and brain TLR-4 modulation following N-acetyl-cysteine treatment in NEC rodent model. Scientific Reports 13:1.
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Blake A. Froberg. 2023. Caring for the Hospitalized Child: A Handbook of Inpatient Pediatrics. Caring for the Hospitalized Child: A Handbook of Inpatient Pediatrics.
James W. Dear. (2022) Fomepizole should not be used more liberally in paracetamol overdose. British Journal of Clinical Pharmacology 89:2, pages 599-601.
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Ari B. Filip & Michael E. Mullins. (2022) Fomepizole should be used more liberally in paracetamol overdose. British Journal of Clinical Pharmacology 89:2, pages 594-598.
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D. Nicholas Bateman. (2022) Large paracetamol overdose—Higher dose acetylcysteine is required. British Journal of Clinical Pharmacology 89:1, pages 34-38.
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H. K. Ruben Thanacoody. (2022) Large paracetamol overdose – Higher dose NAC is NOT required. British Journal of Clinical Pharmacology 89:1, pages 39-42.
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Yi Ding, Qiulin Luo, Hanyun Que, Nan Wang, Puyang Gong & Jian Gu. (2022) Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Agent for the Treatment of Liver Diseases. International Journal of Molecular Sciences 23:18, pages 10972.
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Jerly Maybelline Díaz Herrera, Lady Paola Castellanos Avendaño & Javier Roberto Rodríguez Buitrago. (2022) Intoxicación aguda por acetaminofén en atención primaria. Revista Med 29:2, pages 79-92.
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Jin-cheng Wang, Qi Shi, Qian Zhou, Lu-lu Zhang, Yue-ping Qiu, Da-yong Lou, Li-qin Zhou, Bo Yang, Qiao-jun He, Qin-jie Weng & Jia-jia Wang. (2022) Sapidolide A alleviates acetaminophen-induced acute liver injury by inhibiting NLRP3 inflammasome activation in macrophages. Acta Pharmacologica Sinica 43:8, pages 2016-2025.
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Yang Yao, Rong Li, Dan Liu, Lihui Long & Na He. (2022) Rosmarinic acid alleviates acetaminophen-induced hepatotoxicity by targeting Nrf2 and NEK7-NLRP3 signaling pathway. Ecotoxicology and Environmental Safety 241, pages 113773.
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Jincheng Wang, Lulu Zhang, Qi Shi, Bo Yang, Qiaojun He, Jiajia Wang & Qinjie Weng. (2022) Targeting innate immune responses to attenuate acetaminophen-induced hepatotoxicity. Biochemical Pharmacology 202, pages 115142.
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Lifang Jin, Merveille Chancelle Kom, Guoquan Fu, Yixia Xie, Yue Gao, Jiayuan Shen, Huarong Huang, Baowei Hu & Junyan Yan. (2022) Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal‐regulating kinase 1/c‐Jun amino‐terminal kinase signaling. Environmental Toxicology 37:6, pages 1288-1296.
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Ali Mohammad Pourbagher-Shahri, Jonathan Schimmel, Farshad M. Shirazi, Samaneh Nakhaee & Omid Mehrpour. (2022) Use of fomepizole (4-methylpyrazole) for acetaminophen poisoning: A scoping review. Toxicology Letters 355, pages 47-61.
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Jephte Y. Akakpo, Anup Ramachandran, Steven C. Curry, Barry H. Rumack & Hartmut Jaeschke. (2022) Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for acetaminophen overdose. Archives of Toxicology 96:2, pages 453-465.
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Yaping Wang, William M. Pandak, Edward J. Lesnefsky, Phillip B. Hylemon & Shunlin Ren. (2021) 25-Hydroxycholesterol 3-Sulfate Recovers Acetaminophen Induced Acute Liver Injury via Stabilizing Mitochondria in Mouse Models. Cells 10:11, pages 3027.
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Christopher McCudden, Edward G. Clark, Ayub Akbari, Jennifer Kong, Salmaan Kanji & Swapnil Hiremath. (2021) N-Acetylcysteine Interference With Creatinine Measurement: An In Vitro Analysis. Kidney International Reports 6:7, pages 1973-1976.
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Angela L. Chiew & Nicholas A. Buckley. (2021) Acetaminophen Poisoning. Critical Care Clinics 37:3, pages 543-561.
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Gunn-Guang Liou, Cheng-Chi Hsieh, Yi-Ju Lee, Pin-Hung Li, Ming-Shiun Tsai, Chi-Ting Li & Sue-Hong Wang. (2021) N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice. Antioxidants 10:3, pages 442.
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Kristen M. Audley & Jamie M. Rosini. (2020) Increased Intravenous N-Acetylcysteine Dosing Following Massive Acetaminophen Ingestion: A Case Report. Journal of Emergency Nursing 46:3, pages 359-363.
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Angela L Chiew, David Reith, Adam Pomerleau, Anselm Wong, Katherine Z Isoardi, Jessamine Soderstrom & Nicholas A Buckley. (2019) Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. Medical Journal of Australia 212:4, pages 175-183.
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Robert S. Hoffman. (2020) Acetylcysteine for paracetamol: Will one size ever fit all?. EClinicalMedicine 20, pages 100314.
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Jordan A. Woolum, William B. Hays & Kripa H. Patel. (2020) Use of fomepizole, n-acetylcysteine, and hemodialysis for massive acetaminophen overdose. The American Journal of Emergency Medicine 38:3, pages 692.e5-692.e7.
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Yang Feng, Ruixia Cui, Zeyu Li, Xia Zhang, Yifan Jia, Xing Zhang, Jinghong Shi, Kai Qu, Chang Liu & Jingyao Zhang. (2019) Methane Alleviates Acetaminophen-Induced Liver Injury by Inhibiting Inflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis through the Nrf2/HO-1/NQO1 Signaling Pathway. Oxidative Medicine and Cellular Longevity 2019, pages 1-14.
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Juan Tan, Jing Li, Jilei Ma & Feng Qiao. (2019) Hepatoprotective effect of essential oils of Nepeta cataria L. on acetaminophen-induced liver dysfunction . Bioscience Reports 39:8.
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Tom MunyerAmberly Johnson. 2017. PharmacotherapyFirst: A Multimedia Learning Resource. PharmacotherapyFirst: A Multimedia Learning Resource.

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