Editing Paracetamol (section)

==Overdose==
{{Main|Paracetamol poisoning}}
[[Drug overdose|Overdose]] of paracetamol is caused by taking more than the recommended maximum daily dose of paracetamol for healthy adults (three or four grams),<ref name=UK2017/> and can cause potentially fatal [[Hepatotoxicity|liver damage]].<ref>{{cite web |title=Acetaminophen Information |website=U.S. [[Food and Drug Administration]] |date=14 November 2017 |url=https://www.fda.gov/drugs/information-drug-class/acetaminophen-information |archive-url= https://web.archive.org/web/20191028022254/https://www.fda.gov/drugs/information-drug-class/acetaminophen-information |archive-date=28 October 2019 |url-status=live |access-date=27 October 2019}}{{PD-notice}}</ref><ref>{{cite web |title=Using Acetaminophen and Nonsteroidal Anti-inflammatory Drugs Safely |website=U.S. [[Food and Drug Administration]] (FDA) |date=26 February 2018 |url=https://www.fda.gov/drugs/safe-use-over-counter-pain-relievers-and-fever-reducers/using-acetaminophen-and-nonsteroidal-anti-inflammatory-drugs-safely |archive-url=https://web.archive.org/web/20191028025936/https://www.fda.gov/drugs/safe-use-over-counter-pain-relievers-and-fever-reducers/using-acetaminophen-and-nonsteroidal-anti-inflammatory-drugs-safely |archive-date=28 October 2019 |url-status=live |access-date=27 October 2019}}{{PD-notice}}</ref> A single dose should not exceed 1000&nbsp;mg, doses should be taken no sooner than four hours apart, and no more than four doses (4000&nbsp;mg) in 24 hours.<ref name=UK2017/> While a majority of adult overdoses are linked to suicide attempts, many cases are accidental, often due to the use of more than one paracetamol-containing product over an extended period.<ref>{{cite journal | vauthors = Amar PJ, Schiff ER | title = Acetaminophen safety and hepatotoxicity--where do we go from here? | journal = Expert Opinion on Drug Safety | volume = 6 | issue = 4 | pages = 341–355 | date = July 2007 | pmid = 17688378 | doi = 10.1517/14740338.6.4.341 | s2cid = 20399748 }}</ref>

[[Paracetamol toxicity]] has become the foremost cause of acute liver failure in the United States by 2003,<ref name="Larson2005" /> and {{As of|2005|lc=y}}, paracetamol accounted for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand.<ref>{{cite journal | vauthors = Buckley N, Eddleston M | title = Paracetamol (acetaminophen) poisoning | journal = Clinical Evidence | issue = 14 | pages = 1738–1744 | date = December 2005 | pmid = 16620471 | url = https://pubmed.ncbi.nlm.nih.gov/16620471/ }}</ref> As of 2004, paracetamol overdose resulted in more calls to [[poison control center]]s in the U.S. than overdose of any other pharmacological substance.<ref name="Lee2004">{{cite journal |vauthors=Lee WM |title=Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure |journal=Hepatology |volume=40 |issue=1 |pages=6–9 |year=2004 |pmid=15239078 |doi=10.1002/hep.20293|s2cid=15485538 |doi-access=free |title-link = doi }}</ref> According to the FDA, in the United States, "56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year [were] related to acetaminophen-associated overdoses during the 1990s. Within these estimates, unintentional acetaminophen overdose accounted for nearly 25% of the emergency department visits, 10% of the hospitalizations, and 25% of the deaths."<ref>{{cite web| publisher=US Food and Drug Administration| date=14 January 2011| website=regulations.gov| url=http://www.regulations.gov/#!documentDetail;D=FDA-2011-N-0021-0001 |title=Prescription Drug Products Containing Acetaminophen: Actions to Reduce Liver Injury from Unintentional Overdose| archive-url=https://web.archive.org/web/20120925153342/http://www.regulations.gov/ |archive-date=25 September 2012 |access-date=23 February 2014}}{{PD-notice}}</ref>{{needs update|date=February 2024}}

Overdoses are frequently related to high-dose [[Recreational drug use|recreational use]] of prescription [[opioids]], as these opioids are most often combined with paracetamol.<ref>{{cite news |url=https://www.cnn.com/2014/01/15/health/fda-acetaminophen-dosage/index.html |vauthors=Yan H |title=FDA: Acetaminophen doses over 325 mg may lead to liver damage |publisher=[[CNN]] |access-date=18 February 2014 |date=16 January 2014 |url-status=live |archive-url= https://web.archive.org/web/20140216091112/http://www.cnn.com/2014/01/15/health/fda-acetaminophen-dosage/index.html?hpt=hp_t2 |archive-date=16 February 2014}}</ref> The overdose risk may be heightened by frequent consumption of alcohol.<ref name="Lee2017">{{cite journal |vauthors=Lee WM |title=Acetaminophen (APAP) hepatotoxicity—Isn't it time for APAP to go away? |journal=Journal of Hepatology |volume=67 |issue=6 |pages=1324–1331 |date=December 2017 |pmid=28734939 |pmc=5696016 |doi=10.1016/j.jhep.2017.07.005}}</ref>

Untreated paracetamol overdose results in a lengthy, painful illness. Signs and symptoms of paracetamol toxicity may initially be absent or [[non-specific symptom]]s. The first symptoms of overdose usually begin several hours after ingestion, with [[nausea]], [[vomiting]], sweating, and pain as acute liver failure starts.<ref name="Rumack1975">{{cite journal |vauthors=Rumack B, Matthew H |title=Acetaminophen poisoning and toxicity |journal=Pediatrics |volume=55 |issue=6 |pages=871–876 |year=1975 |doi=10.1542/peds.55.6.871 |pmid=1134886| s2cid=45739342}}</ref> People who take overdoses of paracetamol do not fall asleep or lose consciousness, although most people who attempt suicide with paracetamol wrongly believe that they will be rendered unconscious by the drug.<ref>{{cite web|title=Paracetamol|date=25 March 2013|url=http://cebmh.warne.ox.ac.uk/csr/resparacet.html |publisher=University of Oxford Centre for Suicide Research |access-date=20 April 2013|url-status=dead|archive-url= https://web.archive.org/web/20130320041145/http://cebmh.warne.ox.ac.uk/csr/resparacet.html|archive-date=20 March 2013}}</ref><ref name="met1">{{cite web |vauthors=Mehta S |title=Metabolism of Paracetamol (Acetaminophen), Acetanilide and Phenacetin |website=PharmaXChange.info |date=25 August 2012 |url= https://pharmaxchange.info/2012/08/metabolism-of-paracetamol-acetaminophen-acetanilide-and-phenacetin/ |access-date=27 October 2019 |url-status=dead |archive-url= https://web.archive.org/web/20191028061441/https://pharmaxchange.info/2012/08/metabolism-of-paracetamol-acetaminophen-acetanilide-and-phenacetin/ |archive-date=28 October 2019}}</ref>

Treatment is aimed at removing the paracetamol from the body and replenishing [[glutathione]].<ref name="met1"/> [[Activated charcoal]] can be used to decrease absorption of paracetamol if the person comes to the hospital soon after the overdose. While the antidote, [[acetylcysteine]] (also called ''N''-acetylcysteine or NAC), acts as a precursor for glutathione, helping the body regenerate enough to prevent or at least decrease the possible damage to the liver; a [[liver transplant]] is often required if damage to the liver becomes severe.<ref name="Daly2008"/><ref>{{cite web |url=http://acetadote.com/Acetadote21-539-12_PI_Clean_June2013.pdf |title=Highlights of Prescribing Information |publisher=Acetadote |access-date=10 February 2014 |url-status=dead |archive-url= https://web.archive.org/web/20140222012224/http://acetadote.com/Acetadote21-539-12_PI_Clean_June2013.pdf |archive-date=22 February 2014 }}</ref>

NAC was usually given following a treatment [[nomogram]] (one for people with risk factors, and one for those without), but the use of the nomogram is no longer recommended as evidence to support the use of risk factors was poor and inconsistent, and many of the risk factors are imprecise and difficult to determine with sufficient certainty in clinical practice.<ref>{{cite web|title=Paracetamol overdose: new guidance on treatment with intravenous acetylcysteine |website=Drug Safety Update |date=September 2012 |volume=6 |issue=2 |pages=A1 |url=http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON185624 |archive-url=https://web.archive.org/web/20121027163355/http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON185624 |url-status=dead |archive-date=27 October 2012}}</ref><ref>{{cite web |title=Treating paracetamol overdose with intravenous acetylcysteine: new guidance |website=GOV.UK |date=11 December 2014 |url=https://www.gov.uk/drug-safety-update/treating-paracetamol-overdose-with-intravenous-acetylcysteine-new-guidance |access-date=24 January 2021 |archive-date=28 October 2019 |url-status=live |archive-url=https://web.archive.org/web/20191028073251/https://www.gov.uk/drug-safety-update/treating-paracetamol-overdose-with-intravenous-acetylcysteine-new-guidance}}</ref> Toxicity of paracetamol is due to its [[1,4-Benzoquinone|quinone metabolite]] [[NAPQI]] and NAC also helps in neutralizing it.<ref name="met1" /> [[Kidney failure]] is also a possible side effect.<ref name="Lee2017" />