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Acetaminophen (paracetamol) poisoning in adults: Treatment

Kennon Heard, MD
Richard Dart, MD, PhD
Section Editor
Stephen J Traub, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM


Acetaminophen (APAP) poisoning is among the most common causes of medication-related poisoning and death. Acetaminophen poisoning may occur following a single acute ingestion or through the repeated ingestion of supratherapeutic amounts. The management of the acetaminophen-poisoned patient may include stabilization, decontamination, and administration of N-acetylcysteine, a specific antidote. The duration of N-acetylcysteine treatment is determined by the type of ingestion and the presence or absence of elevated serum alanine aminotransferase (ALT) concentrations.

The treatment of APAP poisoning is reviewed here. The diagnosis of APAP poisoning, both acute and chronic, and the management of hepatic injury or failure are discussed separately. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis" and "Acute liver failure in adults: Management and prognosis".)


The initial management of acetaminophen poisoning is determined by the patient's presenting symptoms. Most patients who present early (within 24 hours) after an acute acetaminophen ingestion are asymptomatic, while others may require treatment for symptoms related to coingestants.

As there are no early symptoms that predict acetaminophen toxicity, poisoning severity following an acute ingestion is quantified by plotting a timed serum acetaminophen concentration on the modified Rumack-Matthew nomogram (figure 1). Patients with serum acetaminophen concentrations that fall above the treatment line following an acute overdose are treated with N-acetylcysteine. In addition, N-acetylcysteine is given to all patients at significant risk for hepatotoxicity following an ingestion of acetaminophen. (See 'Antidote: acetylcysteine' below.)

Use of the nomogram, as well as risk factors for hepatotoxicity and the diagnosis of both acute and chronic acetaminophen poisoning, are discussed separately. A summary table to facilitate emergent management is provided (table 1). (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis".)


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Literature review current through: Sep 2016. | This topic last updated: Aug 30, 2016.
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  1. Brok J, Buckley N, Gluud C. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev 2006; :CD003328.
  2. Underhill TJ, Greene MK, Dove AF. A comparison of the efficacy of gastric lavage, ipecacuanha and activated charcoal in the emergency management of paracetamol overdose. Arch Emerg Med 1990; 7:148.
  3. Spiller HA, Krenzelok EP, Grande GA, et al. A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose. Ann Emerg Med 1994; 23:519.
  4. Buckley NA, Whyte IM, O'Connell DL, Dawson AH. Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. J Toxicol Clin Toxicol 1999; 37:753.
  5. Spiller HA, Winter ML, Klein-Schwartz W, Bangh SA. Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. J Emerg Med 2006; 30:1.
  6. Bond GR, Requa RK, Krenzelok EP, et al. Influence of time until emesis on the efficacy of decontamination using acetaminophen as a marker in a pediatric population. Ann Emerg Med 1993; 22:1403.
  7. Position paper: Ipecac syrup. J Toxicol Clin Toxicol 2004; 42:133.
  8. Grierson R, Green R, Sitar DS, Tenenbein M. Gastric lavage for liquid poisons. Ann Emerg Med 2000; 35:435.
  9. Vale JA, Kulig K, American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position paper: gastric lavage. J Toxicol Clin Toxicol 2004; 42:933.
  10. Smilkstein MJ, Bronstein AC, Linden C, et al. Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. Ann Emerg Med 1991; 20:1058.
  11. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988; 319:1557.
  12. Prescott LF. Treatment of severe acetaminophen poisoning with intravenous acetylcysteine. Arch Intern Med 1981; 141:386.
  13. Vale JA, Meredith TJ, Goulding R. Treatment of acetaminophen poisoning. The use of oral methionine. Arch Intern Med 1981; 141:394.
  14. Rumack BH, Peterson RC, Koch GG, Amara IA. Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med 1981; 141:380.
  15. Prescott LF, Park J, Ballantyne A, et al. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 1977; 2:432.
  16. Heard K, Rumack BH, Green JL, et al. A single-arm clinical trial of a 48-hour intravenous N-acetylcysteine protocol for treatment of acetaminophen poisoning. Clin Toxicol (Phila) 2014; 52:512.
  17. Keays R, Harrison PM, Wendon JA, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991; 303:1026.
  18. Harrison PM, Keays R, Bray GP, et al. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. Lancet 1990; 335:1572.
  19. Harrison PM, Wendon JA, Gimson AE, et al. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med 1991; 324:1852.
  20. Schwartz EA, Hayes BD, Sarmiento KF. Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine. Ann Emerg Med 2009; 54:421.
  21. Wang GS, Monte A, Bagdure D, Heard K. Hepatic failure despite early acetylcysteine following large acetaminophen-diphenhydramine overdose. Pediatrics 2011; 127:e1077.
  22. Woodhead JL, Howell BA, Yang Y, et al. An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury. J Pharmacol Exp Ther 2012; 342:529.
  23. Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila) 2012; 50:91.
  24. Wong A, Graudins A. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. Clin Toxicol (Phila) 2016; 54:115.
  25. Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet 2014; 383:697.
  26. Green JL, Heard KJ, Reynolds KM, Albert D. Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis. West J Emerg Med 2013; 14:218.
  27. Schwarz E, Cohn B. Is intravenous acetylcysteine more effective than oral administration for the prevention of hepatotoxicity in acetaminophen overdose? Ann Emerg Med 2014; 63:79.
  28. Acetylcysteine oral solution: dosage and administration. http://www.rxlist.com/acetylcysteine-solution-drug.htm (Accessed on February 09, 2011).
  29. Mucomyst prescribing instructions for acetaminophen overdose. Revised 24 January 2001. http://www.rxlist.com/acetylcysteine-solution-drug.htm (Accessed on February 09, 2011).
  30. Cumberland Pharmaceuticals. [Physician Letter - Acetadote® (acetylcysteine) Injection: Dosing in Patients Weighing over 100 kg]. 9.28.06. Available from: Cumberland Pharmaceuticals info@cumberlandpharma.com.
  31. Varney SM, Buchanan JA, Heard K. Acetylcysteine (NAC) Use for Acetaminophen (APAP) Overdose in Patients Weighing over 100 kg (abstract). Clin Toxicol 47:738.
  32. Hayes BD, Klein-Schwartz W, Doyon S. Frequency of medication errors with intravenous acetylcysteine for acetaminophen overdose. Ann Pharmacother 2008; 42:766.
  33. Kerr F, Dawson A, Whyte IM, et al. The Australasian Clinical Toxicology Investigators Collaboration randomized trial of different loading infusion rates of N-acetylcysteine. Ann Emerg Med 2005; 45:402.
  34. Dawson AH, Henry DA, McEwen J. Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. Med J Aust 1989; 150:329.
  35. Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med 1998; 31:710.
  36. Yip L, Dart RC. A 20-hour treatment for acute acetaminophen overdose. N Engl J Med 2003; 348:2471.
  37. Clark RF, Chen R, Williams SR, et al. The use of ondansetron in the treatment of nausea and vomiting associated with acetaminophen poisoning. J Toxicol Clin Toxicol 1996; 34:163.
  38. Smith SW, Howland MA, Hoffman RS, Nelson LS. Acetaminophen overdose with altered acetaminophen pharmacokinetics and hepatotoxicity associated with premature cessation of intravenous N-acetylcysteine therapy. Ann Pharmacother 2008; 42:1333.
  39. Doyon S, Klein-Schwartz W. Hepatotoxicity despite early administration of intravenous N-acetylcysteine for acute acetaminophen overdose. Acad Emerg Med 2009; 16:34.
  40. Dart RC, Rumack BH. Patient-tailored acetylcysteine administration. Ann Emerg Med 2007; 50:280.
  41. Betten DP, Cantrell FL, Thomas SC, et al. A prospective evaluation of shortened course oral N-acetylcysteine for the treatment of acute acetaminophen poisoning. Ann Emerg Med 2007; 50:272.
  42. Daly FF, O'Malley GF, Heard K, et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med 2004; 44:393.
  43. Daly FF, Fountain JS, Murray L, et al. Guidelines for the management of paracetamol poisoning in Australia and New Zealand--explanation and elaboration. A consensus statement from clinical toxicologists consulting to the Australasian poisons information centres. Med J Aust 2008; 188:296.
  44. Wallace CI, Dargan PI, Jones AL. Paracetamol overdose: an evidence based flowchart to guide management. Emerg Med J 2002; 19:202.
  45. Bailey B, Amre DK, Gaudreault P. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med 2003; 31:299.
  46. Whyte IM, Buckley NA, Reith DM, et al. Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII. Ther Drug Monit 2000; 22:742.
  47. Fontana RJ. Acute liver failure including acetaminophen overdose. Med Clin North Am 2008; 92:761.
  48. Cairney DG, Beckwith HK, Al-Hourani K, et al. Plasma paracetamol concentration at hospital presentation has a dose-dependent relationship with liver injury despite prompt treatment with intravenous acetylcysteine. Clin Toxicol (Phila) 2016; 54:405.
  49. Riggs BS, Bronstein AC, Kulig K, et al. Acute acetaminophen overdose during pregnancy. Obstet Gynecol 1989; 74:247.
  50. Haibach H, Akhter JE, Muscato MS, et al. Acetaminophen overdose with fetal demise. Am J Clin Pathol 1984; 82:240.
  51. McElhatton PR, Sullivan FM, Volans GN. Paracetamol overdose in pregnancy analysis of the outcomes of 300 cases referred to the Teratology Information Service. Reprod Toxicol 1997; 11:85.
  52. Stokes IM. Paracetamol overdose in the second trimester of pregnancy. Case report. Br J Obstet Gynaecol 1984; 91:286.
  53. Rosevear SK, Hope PL. Favourable neonatal outcome following maternal paracetamol overdose and severe fetal distress. Case report. Br J Obstet Gynaecol 1989; 96:491.
  54. Lederman S, Fysh WJ, Tredger M, Gamsu HR. Neonatal paracetamol poisoning: treatment by exchange transfusion. Arch Dis Child 1983; 58:631.
  55. McElhatton PR, Sullivan FM, Volans GN, Fitzpatrick R. Paracetamol poisoning in pregnancy: an analysis of the outcomes of cases referred to the Teratology Information Service of the National Poisons Information Service. Hum Exp Toxicol 1990; 9:147.
  56. Horowitz RS, Dart RC, Jarvie DR, et al. Placental transfer of N-acetylcysteine following human maternal acetaminophen toxicity. J Toxicol Clin Toxicol 1997; 35:447.
  57. Roberts I, Robinson MJ, Mughal MZ, et al. Paracetamol metabolites in the neonate following maternal overdose. Br J Clin Pharmacol 1984; 18:201.
  58. Sancewicz-Pach K, Chmiest W, Lichota E. Suicidal paracetamol poisoning of a pregnant woman just before a delivery. Przegl Lek 1999; 56:459.
  59. Wang PH, Yang MJ, Lee WL, et al. Acetaminophen poisoning in late pregnancy. A case report. J Reprod Med 1997; 42:367.
  60. Speeg KV Jr, Mitchell MC, Maldonado AL. Additive protection of cimetidine and N-acetylcysteine treatment against acetaminophen-induced hepatic necrosis in the rat. J Pharmacol Exp Ther 1985; 234:550.
  61. Mitchell MC, Schenker S, Speeg KV Jr. Selective inhibition of acetaminophen oxidation and toxicity by cimetidine and other histamine H2-receptor antagonists in vivo and in vitro in the rat and in man. J Clin Invest 1984; 73:383.
  62. Al-Mustafa ZH, Al-Ali AK, Qaw FS, Abdul-Cader Z. Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice treated with toxic doses of paracetamol. Toxicology 1997; 121:223.
  63. Peterson FJ, Knodell RG, Lindemann NJ, Steele NM. Prevention of acetaminophen and cocaine hepatotoxicity in mice by cimetidine treatment. Gastroenterology 1983; 85:122.
  64. Mitchell MC, Schenker S, Avant GR, Speeg KV Jr. Cimetidine protects against acetaminophen hepatotoxicity in rats. Gastroenterology 1981; 81:1052.
  65. Burkhart KK, Janco N, Kulig KW, Rumack BH. Cimetidine as adjunctive treatment for acetaminophen overdose. Hum Exp Toxicol 1995; 14:299.
  66. Chen X, Sun CK, Han GZ, et al. Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression. World J Gastroenterol 2009; 15:1829.
  67. Reisman SA, Aleksunes LM, Klaassen CD. Oleanolic acid activates Nrf2 and protects from acetaminophen hepatotoxicity via Nrf2-dependent and Nrf2-independent processes. Biochem Pharmacol 2009; 77:1273.
  68. Chen YH, Lin FY, Liu PL, et al. Antioxidative and hepatoprotective effects of magnolol on acetaminophen-induced liver damage in rats. Arch Pharm Res 2009; 32:221.
  69. Küçükardali Y, Cinan U, Acar HV, et al. Comparison of the therapeutic efficacy of 4-methylpyrazole and N-acetylcysteine on acetaminophen (paracetamol) hepatotoxicity in rats. Curr Med Res Opin 2002; 18:78.
  70. Prescott LF, Sutherland GR, Park J, et al. Cysteamine, methionine, and penicillamine in the treatment of paracetamol poisoning. Lancet 1976; 2:109.
  71. Hamlyn AN, Lesna M, Record CO, et al. Methionine and cysteamine in paracetamol (acetaminophen) overdose, prospective controlled trial of early therapy. J Int Med Res 1981; 9:226.
  72. Wu ML, Tsai WJ, Deng JF, Yang CC. Hemodialysis as adjunctive therapy for severe acetaminophen poisoning: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1999; 62:907.
  73. Marbury TC, Wang LH, Lee CS. Hemodialysis of acetaminophen in uremic patients. Int J Artif Organs 1980; 3:263.
  74. Gosselin S, Juurlink DN, Kielstein JT, et al. Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup. Clin Toxicol (Phila) 2014; 52:856.
  75. Sivilotti ML, Juurlink DN, Garland JS, et al. Antidote removal during haemodialysis for massive acetaminophen overdose. Clin Toxicol (Phila) 2013; 51:855.
  76. Hernandez SH, Howland M, Schiano TD, Hoffman RS. The pharmacokinetics and extracorporeal removal of N-acetylcysteine during renal replacement therapies. Clin Toxicol (Phila) 2015; 53:941.
  77. Prescott LF, Illingworth RN, Critchley JA, et al. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J 1979; 2:1097.
  78. Spooner, JB, Harvey, JG. Paracetamol overdose — Facts not misconceptions. Pharm J 1993; 251:706.
  79. Antoine DJ, Dear JW, Lewis PS, et al. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology 2013; 58:777.
  80. Wong A, Sivilotti ML, Dargan PI, et al. External validation of the paracetamol-aminotransferase multiplication product to predict hepatotoxicity from paracetamol overdose. Clin Toxicol (Phila) 2015; 53:807.