Editing Fentanyl (section)

== History ==
Fentanyl was first synthesized in Belgium by [[Paul Janssen]] under the label of his relatively newly formed [[Janssen Pharmaceutica]] in 1959.<ref name=JanssenHist>{{cite journal | vauthors = López-Muñoz F, Alamo C | title = The consolidation of neuroleptic therapy: Janssen, the discovery of haloperidol and its introduction into clinical practice | journal = Brain Research Bulletin | volume = 79 | issue = 2 | pages = 130–141 | date = April 2009 | pmid = 19186209 | doi = 10.1016/j.brainresbull.2009.01.005 | s2cid = 7720401 }}</ref> It was developed by screening chemicals similar to [[pethidine]] (Demerol) for opioid activity.<ref name="Bla2005">{{cite journal | vauthors = Black J | title = A personal perspective on Dr. Paul Janssen | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 6 | pages = 1687–1688 | date = March 2005 | pmid = 15771410 | doi = 10.1021/jm040195b | url = http://www.pauljanssenaward.com/janssen/A_Personal_Perspective.pdf#zoom=100 | url-status = dead | archive-url = https://web.archive.org/web/20071010091139/http://www.pauljanssenaward.com/janssen/A_Personal_Perspective.pdf | archive-date = 10 October 2007 }}</ref> The widespread use of fentanyl triggered the production of fentanyl citrate (the salt formed by combining fentanyl and citric acid in a 1:1 [[stoichiometry|stoichiometric ratio]]).<ref>{{cite web | title=Sublimaze- fentanyl citrate injection, solution | website=DailyMed | date=21 April 2008 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8944ea18-016e-4971-876d-2365fac190ea | access-date=10 July 2024}}</ref><ref>{{cite web | title=Actiq- fentanyl citrate lozenge | website=DailyMed | date=18 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90b94524-f913-48b3-3771-7b2fcffd888a | access-date=10 July 2024}}</ref> Fentanyl citrate entered medical use as a general anaesthetic in 1968, manufactured by [[McNeil Consumer Healthcare|McNeil Laboratories]] under the brand name Sublimaze.<ref>{{cite journal | vauthors = | title = Fentanyl (sublimaze) | journal = Clinical Pharmacology and Therapeutics | volume = 9 | issue = 5 | pages = 704–706 | date = September 1968 | pmid = 5676808 | doi = 10.1002/cpt196895704 | s2cid = 9743189 }}</ref>

In the mid-1990s, Janssen Pharmaceutica developed and introduced into clinical trials the Duragesic patch, which is a formulation of an inert alcohol gel infused with select fentanyl doses, which are worn to provide constant administration of the opioid over 48 to 72{{nbsp}}hours. After a set of successful clinical trials, Duragesic fentanyl patches were introduced into medical practice.<ref>{{cite web |vauthors=Mandal A |veditors=SRobertson S |title=Fentanyl History |url=https://www.news-medical.net/health/Fentanyl-History.aspx |website=News-Medical.net |publisher=AZoNetwork |access-date=27 January 2023 |date=11 April 2010 |archive-date=27 January 2023 |archive-url=https://web.archive.org/web/20230127211932/https://www.news-medical.net/health/Fentanyl-History.aspx |url-status=live }}</ref>

Following the patch, a flavored [[buccal administration|lollipop]] of fentanyl citrate mixed with inert fillers was introduced in 1998 under the brand name Actiq, becoming the first quick-acting formation of fentanyl for use with chronic breakthrough pain.<ref>{{cite web|title=ACTIQ® (fentanyl citrate) oral transmucosal lozenge (1968 version revised in 2011)|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020747s033lbl.pdf|publisher=U.S. [[Food and Drug Administration]] (FDA) |access-date=26 December 2017|date=December 2011|archive-url=https://web.archive.org/web/20170210123603/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020747s033lbl.pdf|archive-date=10 February 2017|url-status=live}}</ref>

In 2009, the US [[Food and Drug Administration]] (FDA) approved Onsolis (fentanyl buccal soluble film), a fentanyl drug in a new dosage form for cancer pain management in opioid-tolerant subjects.<ref name="onsolis">{{cite web|title=Questions and Answers about Onsolis (fentanyl buccal soluble film)|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm172039.htm|publisher=U.S. [[Food and Drug Administration]] (FDA) |access-date=26 December 2017|date=16 July 2009|archive-url=https://web.archive.org/web/20170722191120/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm172039.htm|archive-date=22 July 2017|url-status=dead}}</ref> It uses a medication delivery technology called BEMA (BioErodible MucoAdhesive), a small dissolvable polymer film containing various fentanyl doses applied to the inner lining of the [[cheek]].<ref name=onsolis/>

Fentanyl has a US [[Drug Enforcement Administration]] (DEA) [[Administrative Controlled Substances Code Number]] (ACSCN) of 9801. Its annual aggregate manufacturing quota has significantly reduced in recent years from 2,300,000{{nbsp}}kg in 2015 and 2016 to only 731,452{{nbsp}}kg in 2021, a nearly 68.2% decrease.<ref>{{cite web |title=2022 Aggregate Production Quota History for Selected Substances |url=https://www.deadiversion.usdoj.gov/quotas/quota_history.pdf |archive-url=https://web.archive.org/web/20230119052906/https://www.deadiversion.usdoj.gov/quotas/quota_history.pdf |archive-date=19 January 2023 |url-status=live}}</ref>