Editing Fentanyl (section)

== Overdose ==
{{Further|Opioid overdose|U.S. drug overdose death rates and totals over time}}[[File:2 milligrams of fentanyl on pencil tip. A lethal dose for most people. US Drug Enforcement Administration.jpg|thumb|upright=1.0|A two&nbsp;[[milligram]] dose of fentanyl powder (on [[pencil]] tip) is a lethal amount for most people.<ref name=onepill/><ref>{{cite web | url = https://www.dea.gov/galleries/drug-images/fentanyl | archive-url = https://web.archive.org/web/20181008000027/https://www.dea.gov/galleries/drug-images/fentanyl | archive-date = 8 October 2018 | title = Fentanyl. Image 4 of 17 | work = U.S. [[Drug Enforcement Administration]] | quote = photo illustration of 2 milligrams of fentanyl, a lethal dose in most people }}</ref>]]
Fentanyl poses an exceptionally high overdose risk in humans since the amount required to cause [[toxicity]] is unpredictable.<ref name = "Ramos-Matos_2022" /> In its pharmaceutical form, most overdose deaths attributed solely to fentanyl occur at [[Serum (blood)|serum]] concentrations at a mean of 0.025{{nbsp}}μg/mL, with a range 0.005–0.027{{nbsp}}μg/mL.<ref>{{cite journal | vauthors = Cheema E, McGuinness K, Hadi MA, Paudyal V, Elnaem MH, Alhifany AA, Elrggal ME, Al Hamid A | title = Causes, Nature and Toxicology of Fentanyl-Associated Deaths: A Systematic Review of Deaths Reported in Peer-Reviewed Literature | journal = Journal of Pain Research | volume = 13 | pages = 3281–3294 | date = 7 December 2020 | pmid = 33324089 | pmc = 7732170 | doi = 10.2147/JPR.S280462 | doi-access = free | title-link = doi }}</ref> In contexts of poly-substance use, blood fentanyl concentrations of approximately 0.007{{nbsp}} μg/mL or greater have been associated with fatalities.<ref>{{cite web|title=Fentanyl drug profile|publisher=European Monitoring Centre for Drugs and Drug Addiction|url=https://www.emcdda.europa.eu/publications/drug-profiles/fentanyl_en#:~:text=The%20estimated%20lethal%20dose%20of,poly-substance%20use%20was%20involved.|access-date=10 September 2022|archive-date=10 September 2022|archive-url=https://web.archive.org/web/20220910035457/https://www.emcdda.europa.eu/publications/drug-profiles/fentanyl_en#:~:text=The%20estimated%20lethal%20dose%20of,poly-substance%20use%20was%20involved.|url-status=live}}</ref> Over 85% of overdoses involved at least one other drug, and there was no clear correlation showing at which level the mixtures were fatal. The dosages of fatal mixtures varied by over three magnitudes in some cases. This extremely unpredictable volatility with other drugs makes it especially difficult to avoid fatalities.<ref name="pmid31304441">{{cite journal | vauthors = Drummer OH | title = Fatalities caused by novel opioids: a review | journal = Forensic Sciences Research | volume = 4 | issue = 2 | pages = 95–110 | date = 2019 | pmid = 31304441 | pmc = 6609322 | doi = 10.1080/20961790.2018.1460063 }}</ref>

[[Naloxone]] (sold under the brand name Narcan) can completely or partially reverse an opioid overdose.<ref>{{cite web |title=Narcan (Naloxone hydrochloride injection) |website=RxList |url=https://www.rxlist.com/narcan-side-effects-drug-center.htm |access-date=3 March 2020 |archive-date=24 October 2019 |archive-url=https://web.archive.org/web/20191024004929/https://www.rxlist.com/narcan-side-effects-drug-center.htm |url-status=live }}</ref> In July{{nbsp}}2014, the [[Medicines and Healthcare products Regulatory Agency]] (MHRA) of the UK issued a warning about the potential for life-threatening harm from accidental exposure to transdermal fentanyl patches, particularly in children,<ref>{{cite news |title=Fentanyl patches warning |website=[[Pharmaceutical Journal]] |url=http://www.pharmaceutical-journal.com/news-and-analysis/notice-board/fentanyl-patches-warning/20066029.article |access-date=28 March 2016 |archive-url=https://web.archive.org/web/20160408211133/http://www.pharmaceutical-journal.com/news-and-analysis/notice-board/fentanyl-patches-warning/20066029.article |archive-date=8 April 2016 |url-status=live }}</ref> and advised that they should be folded, with the adhesive side in, before being discarded. The patches should be kept away from children, who are most at risk from fentanyl overdose.<ref>{{cite news |title=MHRA warns about fentanyl patches after children exposed |website=[[Pharmaceutical Journal]] |url=http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/mhra-warns-about-fentanyl-patches-after-children-exposed/20065930.article |access-date=28 March 2016 |url-status=live |archive-url=https://web.archive.org/web/20160409000816/http://www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/mhra-warns-about-fentanyl-patches-after-children-exposed/20065930.article |archive-date=9 April 2016 }}</ref> In the US, fentanyl and [[:Category:Synthetic opioids|fentanyl analogs]] caused over 29,000{{nbsp}}deaths in 2017, a large increase over the previous four years.<ref name=NYT2017>{{cite news | vauthors = Katz J |date=2 September 2017 |title=The first count of Fentanyl deaths in 2016 – up 540% in three years |newspaper=[[The New York Times]] |url=https://www.nytimes.com/interactive/2017/09/02/upshot/fentanyl-drug-overdose-deaths.html |access-date=4 September 2017 |url-status=live |archive-url=https://web.archive.org/web/20170904123700/https://www.nytimes.com/interactive/2017/09/02/upshot/fentanyl-drug-overdose-deaths.html |archive-date=4 September 2017 }}</ref><ref name="NIDA-deaths">{{cite report |url=http://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates |title=Overdose Death Rates |date=29 January 2021 |publisher=[[National Institute on Drug Abuse]] (NIDA) |access-date=22 November 2017 |archive-url=https://web.archive.org/web/20151128091723/http://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates |archive-date=28 November 2015 |url-status=live}}</ref>

[[File:Actiq-30-pack-600mcg-fentanyl-base.jpg|thumb|A package of 30 lozenges, 600{{nbsp}}[[Microgram|mcg]] of fentanyl, each]]

Some increases in fentanyl deaths do not involve prescription fentanyl but are related to illicitly made fentanyl that is being mixed with or sold as heroin.<ref>{{cite press release |date=9 August 2021 |title=Reported law enforcement encounters testing positive for Fentanyl increase across U.S. |publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) |url=https://www.cdc.gov/drugoverdose/deaths/fentanyl-encounters/index.html |access-date=3 March 2022 |archive-date=2 March 2022 |archive-url=https://web.archive.org/web/20220302132959/http://www.cdc.gov/drugoverdose/deaths/fentanyl-encounters/index.html |url-status=live }}</ref> Death from fentanyl overdose continues to be a public health issue of national concern in Canada since September 2015.<ref>{{cite news |title=Fentanyl Overdose |date=20 May 2016 |website=[[The Huffington Post]] |url=http://www.huffingtonpost.ca/news/fentanyl-overdose |access-date=4 June 2016 |archive-url=https://web.archive.org/web/20160605035409/http://www.huffingtonpost.ca/news/fentanyl-overdose/ |archive-date=5 June 2016 |url-status=dead }}</ref> In 2016, deaths from fentanyl overdoses in the province of [[British Columbia]] averaged two persons per day.<ref>{{cite report |title=Fentanyl-detected in illicit drug overdose deaths, January 1, 2012 to April 30, 2016 |publisher=British Columbia Coroners Service |url=http://www2.gov.bc.ca/assets/gov/public-safety-and-emergency-services/death-investigation/statistical/fentanyl-detected-overdose.pdf |access-date=9 June 2016 |archive-url=https://web.archive.org/web/20160625235638/http://www2.gov.bc.ca/assets/gov/public-safety-and-emergency-services/death-investigation/statistical/fentanyl-detected-overdose.pdf |archive-date=25 June 2016 |url-status=dead }}</ref> In 2017 the death rate increased by more than 100% with 368 overdose-related deaths in British Columbia between January and April 2017.<ref>{{cite news |title=Fentanyl contributed to hundreds of deaths in Canada so far this year |date=31 July 2017 |website=Global News |url=http://globalnews.ca/news/3637148/fentanyl-overdoses-canada-2017/ |access-date=14 September 2017 |url-status=live |archive-url=https://web.archive.org/web/20170914082850/http://globalnews.ca/news/3637148/fentanyl-overdoses-canada-2017/ |archive-date=14 September 2017 }}</ref>
[[File:FENTANYL FLOW TO THE UNITED STATES 2019.png|thumb|250x250px|Illegal fentanyl flow to the US from various regions in 2019]]
Fentanyl has started to make its way into heroin as well as illicitly manufactured opioids and benzodiazepines. Fentanyl contamination in cocaine, methamphetamine, [[ketamine]], MDMA, and other drugs is common.<ref>{{cite news |vauthors=Scaccia A |date=9 October 2018 |title=How Fentanyl is contaminating America's cocaine supply |magazine=[[Rolling Stone]] |url=https://www.rollingstone.com/culture/culture-features/fentanyl-cocaine-how-contamination-happens-735155/ |access-date=5 November 2018 |archive-date=6 November 2018 |archive-url=https://web.archive.org/web/20181106053222/https://www.rollingstone.com/culture/culture-features/fentanyl-cocaine-how-contamination-happens-735155/ |url-status=live }}</ref><ref>{{cite web |vauthors=Daly M |date=30 July 2019 |title=Exclusive data reveals just how often Fentanyl is in cocaine |website=Vice |url=https://www.vice.com/en/article/how-much-fentanyl-is-actually-in-cocaine/ |access-date=9 January 2020 |archive-date=24 January 2020 |archive-url=https://web.archive.org/web/20200124015237/https://www.vice.com/en_us/article/nea898/how-much-fentanyl-is-actually-in-cocaine |url-status=live }}</ref> A kilogram of heroin laced with fentanyl may sell for more than US$100,000, but the fentanyl itself may be produced far more cheaply, for about US$6,000 per kilogram. While Mexico and China are the primary source countries for fentanyl and fentanyl-related substances trafficked directly into the United States, India is emerging as a source for finished fentanyl powder and fentanyl precursor chemicals.<ref>{{cite news |vauthors=Chang A |date=3 December 2018 |title=What it means for the U.S. that China will label Fentanyl as 'a controlled substance' |publisher=[[NPR]] |department=All Things Considered |url=https://www.npr.org/2018/12/03/673022614/what-it-means-for-the-u-s-that-china-will-label-fentanyl-as-a-controlled-substan |access-date=6 December 2018 |archive-date=6 December 2018 |archive-url=https://web.archive.org/web/20181206025755/https://www.npr.org/2018/12/03/673022614/what-it-means-for-the-u-s-that-china-will-label-fentanyl-as-a-controlled-substan |url-status=live }}</ref><ref name="dea-2020" /> The United Kingdom illicit drug market is no longer reliant on China, as domestic fentanyl production is replacing imports.<ref>{{cite news | vauthors = Grierson J |title=Coronavirus triggers UK shortage of illicit drugs |date=12 April 2020 |department=Society |newspaper=[[The Guardian]] |url=https://www.theguardian.com/society/2020/apr/12/coronavirus-triggers-uk-shortage-of-illicit-drugs |access-date=23 April 2020 |archive-date=9 May 2020 |archive-url=https://web.archive.org/web/20200509113021/https://www.theguardian.com/society/2020/apr/12/coronavirus-triggers-uk-shortage-of-illicit-drugs |url-status=live }}</ref>

The intravenous dose causing 50% of opioid-naive experimental subjects to die ({{LD50}}) is "3{{nbsp}}mg/kg in rats, 1{{nbsp}}mg/kg in cats, 14{{nbsp}}mg/kg in dogs, and 0.03{{nbsp}}mg/kg in monkeys."<ref>{{cite web |title=Fentanyl citrate injection, USP |publisher=U.S. [[Food and Drug Administration]] (FDA) |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016619s034lbl.pdf |access-date=3 March 2019 |archive-date=31 October 2020 |archive-url=https://web.archive.org/web/20201031000544/https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016619s034lbl.pdf |url-status=live }}</ref> The LD<sub>50</sub> in mice has been given as 6.9{{nbsp}}mg/kg by intravenous administration, 17.5{{nbsp}}mg/kg intraperitoneally, 27.8{{nbsp}}mg/kg by oral administration.<ref>{{cite journal | vauthors = Gupta PK, Yadav SK, Bhutia YD, Singh P, Rao P, Gujar NL, Ganesan K, Bhattacharya R |title=Synthesis and comparative bioefficacy of N-(1-phenethyl-4-piperidinyl)propionanilide (fentanyl) and its 1-substituted analogs in Swiss albino mice |journal=Medicinal Chemistry Research |date=1 August 2013 |volume=22 |issue=8 |pages=3888–3896 |doi=10.1007/s00044-012-0390-6 |url=https://link.springer.com/article/10.1007/s00044-012-0390-6 |language=en |issn=1554-8120}}</ref> The LD<sub>50</sub> in humans is unknown.<ref>{{cite web|url=https://www.drugbank.ca/drugs/DB00813|title=Fentanyl|publisher=Drugbank|access-date=18 January 2019|archive-date=11 July 2017|archive-url=https://web.archive.org/web/20170711073330/https://www.drugbank.ca/drugs/DB00813|url-status=live}}</ref>{{Unreliable medical source|date=May 2025}}

In 2023, overdose deaths in the U.S. and Canada again reached record numbers.<ref name="mmwr-2024-12-05">{{cite journal | vauthors = Tanz LJ, Stewart A, Gladden RM, Ko JY, Owens L, O'Donnell J | title = Detection of Illegally Manufactured Fentanyls and Carfentanil in Drug Overdose Deaths – United States, 2021-2024 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 73 | issue = 48 | pages = 1099–1105 | date = December 2024 | pmid = 39636782 | doi = 10.15585/mmwr.mm7348a2 | pmc = 11620336 }}</ref> While overdoses involving fentanyl in the United States have decreased in 2024, the overall percentage of overdoses involving fentanyl has remained stable between 70% and 80% from 2021-2024.<ref name="mmwr-2024-12-05" /> According to a 2023 report from the [[United Nations Office on Drugs and Crime]] (UNODC), the increased numbers of deaths are not related to an increased number of users but to the lethal effects of fentanyl itself. In an article published by [[Los Alamos National Laboratory]], researchers state, "Because of the very high strength of pure fentanyl powder, it’s hard to [[dilute]] precisely, so small inaccuracies in weight can cause huge variation between batches, and it’s all too easy for someone to get too much."<ref>{{Cite web | vauthors = Hutterer E |title=Fighting Fentanyl Overdose and the Opioid Crisis {{!}} LANL |url=https://www.lanl.gov/media/publications/1663/1224-fighting-fentanyl-overdose |access-date=16 April 2025 |website=Eleanor Hutterer |language=en}}</ref>
[[File:US timeline. Opioid deaths.jpg|thumb|Number of yearly U.S. [[opioid overdose]] deaths from all opioid drugs.]]
Fentanyl would require a special status as it is considerably more toxic than other widely abused opioids and opiates.<ref>{{Cite book | author = United Nations Office on Drugs and Crime |url=https://www.unodc.org/res/WDR-2023/WDR23_Exsum_fin_SP.pdf |title=World Drug Report |publisher=United Nations |year=2023 |isbn=9789210028233 |page=44 |quote=The opioid crisis in North America has not been associated with a sizeable increase in the number of opioid users but driven by overdose deaths, mainly attributed to the use of fentanyls. In the United States in 2021, following a year-on-year trend of increase, there were more than 80,000 opioid overdose deaths. Most of those deaths, 70,000, were attributed to any pharmaceutical opioid with synthetic opioids (primarily fentanyls). Women constituted approximately 30 per cent of all those who died from an overdose and of those attributed to opioids in the United States.}}</ref> Overdose deaths in pediatric cases are also concerning. In a report published in [[JAMA Pediatrics]], 37.5% of all fatal pediatric cases between 1999 and 2021 were related to fentanyl; most of the deaths were among adolescents (89.6%) and children aged 0 to 4 years (6.6%). According to the UNODC, "the opioid crisis in North America is unabated, fueled by an unprecedented number of overdose deaths."<ref name="pmid37155161">{{cite journal | vauthors = Gaither JR | title = National Trends in Pediatric Deaths From Fentanyl, 1999-2021 | journal = JAMA Pediatrics | volume = 177 | issue = 7 | pages = 733–735 | date = July 2023 | pmid = 37155161 | pmc = 10167597 | doi = 10.1001/jamapediatrics.2023.0793 | quote = Fentanyl was implicated in 5194 of 13 861 (37.5%) fatal pediatric opioid poisonings between 1999 and 2021. Most deaths were among adolescents aged 15 to 19 years (89.6%) and children aged 0 to 4 years (6.6%). For all ages, 43.8% of deaths occurred at home, and 87.5% were unintentional. Coingestion of benzodiazepines was implicated in 17.1% of deaths [.] }}</ref>

=== Prevention ===
[[File:Fentanyl-test-strip.jpg|thumb|Fentanyl test strip and an instruction manual on reading the result]]
[[File:Fentanyl_Test_Strip_Tutorial.webm|thumb|Fentanyl Test Strip Tutorial]]

Public health advisories to prevent fentanyl misuse and fatal overdose have been issued by the U.S. Centers for Disease Control (CDC). An initial HAN Advisory, also known as a Health Alert Network Advisory ("provides vital, time-sensitive information for a specific incident or situation; warrants immediate action or attention by health officials, laboratorians, clinicians, and members of the public; and conveys the highest level of importance") was issued during October 2015.<ref>{{cite web |title=Increases in Fentanyl Drug Confiscations and Fentanyl-related Overdose Fatalities HAN 00384 |work=Health Alert Network |url=https://emergency.cdc.gov/han/han00384.asp |publisher=U.S. Centers for Disease Control and Prevention |access-date=21 December 2022 |date=15 October 2015 |archive-date=21 December 2022 |archive-url=https://web.archive.org/web/20221221170401/https://emergency.cdc.gov/han/han00384.asp |url-status=live }}</ref> A subsequent HAN Alert was issued in July 2018, warning of rising numbers of deaths due to fentanyl abuse and mixing with non-opioids.<ref>{{cite web |title=Rising Numbers of Deaths Involving Fentanyl and Fentanyl Analogs, Including Carfentanil, and Increased Usage and Mixing with Non-opioids – 00413 |work=Health Alert Network (HAN) |url=https://emergency.cdc.gov/han/han00413.asp |publisher=U.S. Centers for Disease Control and Prevention |access-date=21 December 2022 |date=11 July 2018 |archive-date=21 December 2022 |archive-url=https://web.archive.org/web/20221221170401/https://emergency.cdc.gov/han/han00413.asp |url-status=live }}</ref> A December 2020 HAN Advisory warned of:

<blockquote>substantial increases in drug overdose deaths across the United States, primarily driven by rapid increases in overdose deaths involving ... illicitly manufactured fentanyl; a concerning acceleration of the increase in drug overdose deaths, with the largest increase recorded from March 2020 to May 2020, coinciding with the implementation of widespread mitigation measures for the COVID-19 pandemic; significant increases in overdose deaths involving methamphetamine.<ref name="HAN438">{{cite web |title=Increase in Fatal Drug Overdoses Across the United States Driven by Synthetic Opioids Before and During the COVID-19 Pandemic – HAN 00438 – Health Alert Network Advisory |url=https://emergency.cdc.gov/han/2020/han00438.asp |publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) |access-date=21 December 2022 |date=17 December 2020 |archive-date=20 December 2022 |archive-url=https://web.archive.org/web/20221220222711/https://emergency.cdc.gov/han/2020/han00438.asp |url-status=live }}</ref></blockquote>

81,230 drug overdose deaths occurred during the 12 months from May 2019 to May 2020, the largest number of drug overdoses for a 12-month interval ever recorded for the U.S. The CDC recommended the following four actions to counter this rise:<ref name="HAN438" />
# Local need to expand the distribution and use of naloxone and overdose prevention education,
# Expand awareness, access, and availability of treatment for substance use disorders,
# Intervene early with individuals at the highest risk for overdose, and
# improve detection of overdose outbreaks to facilitate more effective response.<ref name="HAN438" /><ref>{{cite web |date=2 October 2021 |title=Fentanyl {{!}} CDC's Response to the Opioid Overdose Epidemic {{!}} CDC |url=https://www.cdc.gov/opioids/basics/fentanyl.html |access-date=27 April 2022 |publisher=U.S. [[Centers for Disease Control and Prevention]] (CDC) |archive-date=28 April 2022 |archive-url=https://web.archive.org/web/20220428125143/https://www.cdc.gov/opioids/basics/fentanyl.html |url-status=live }}</ref>

Another initiative is a [[social media]] campaign from the United States [[Drug Enforcement Administration]] (DEA) called "One Pill Can Kill".<ref name=onepill>{{cite web |title=One Pill Can Kill |url=https://www.dea.gov/onepill |access-date=15 November 2023 |website=U.S. [[Drug Enforcement Administration]] |archive-date=15 November 2023 |archive-url=https://web.archive.org/web/20231115200822/https://www.dea.gov/onepill |url-status=live}}</ref> This social media campaign's goal is to spread awareness of the prevalence of counterfeit pills that are being sold in America that is leading to the large overdose epidemic in America. This campaign also shows the difference between counterfeit pills and real pills.