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anticodon
{{Distinguish|Naltrexone}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 440816974
| IUPAC_name = (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1''H''-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one
| image = Naloxone.svg
| width = 225px
| image2 = Naloxone-3D-balls.png
| width2 = 250px

<!--Clinical data-->
| tradename = Narcan, Evzio, others
| Drugs.com = {{drugs.com|monograph|naloxone-hydrochloride}}
| licence_EU = yes
| pregnancy_AU = B1
| pregnancy_US = C
| pregnancy_US_comment = <ref name=AHFS2015/>
| pregnancy_category =
| legal_AU = S3
| legal_AU_comment = <ref>{{cite web | url=https://www.theguardian.com/society/2016/jan/29/selling-opioid-overdose-antidote-naloxone-over-counter-will-save-lives | title=Selling opioid overdose antidote Naloxone over counter 'will save lives' | publisher=The Guardian | date=29 January 2016 | author=Melissa Davey | deadurl=no | archiveurl=https://web.archive.org/web/20161203055245/https://www.theguardian.com/society/2016/jan/29/selling-opioid-overdose-antidote-naloxone-over-counter-will-save-lives | archivedate=3 December 2016 | df= }}</ref>
| legal_DE = Anlage 1
| legal_UK = POM
| legal_US = Rx only
| legal_status =
| routes_of_administration = Endotracheal, intranasal, [[Intravenous therapy|IV]], [[Intramuscular|IM]]

<!--Pharmacokinetic data-->
| bioavailability = 2% ([[oral administration|by mouth]], 90% absorption but high [[first-pass metabolism]]) 50% (intranasally)
| protein_bound =
| metabolism = [[Liver]]
| onset = 2 min ({{abbrlink|IV|intravenous injection}}), 5 min ({{abbrlink|IM|intramuscular injection}})<ref name=AHFS2015/>
| elimination_half-life = 1–1.5 h
| duration_of_action= 30–60 min<ref name=AHFS2015/>
| excretion = [[Urine]], [[bile]]


<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 465-65-6
| ATC_prefix = A06
| ATC_suffix = AH04
| ATC_supplemental = <br/>{{ATC|V03|AB15}}
| PubChem = 5284596
| IUPHAR_ligand = 1638
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01183
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4447644
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 36B82AMQ7N
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08249
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 7459
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 80
| synonyms = <small>EN-1530; ''N''-Allylnoroxymorphone; 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one</small>

<!--Chemical data-->
| C=19 | H=21 | N=1 | O=4
| SMILES = O=C1[C@@H]2OC3=C(O)C=CC4=C3[C@@]2([C@]5(CC1)O)CCN(CC=C)[C@@H]5C4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H21NO4/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11/h2-4,14,17,21,23H,1,5-10H2/t14-,17+,18+,19-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UZHSEJADLWPNLE-GRGSLBFTSA-N
}}
<!-- Medical uses -->
'''Naloxone''', sold under the brandname '''Narcan''' among others, is a medication used to block the effects of [[opioids]], especially in [[opioid overdose|overdose]].<ref name=AHFS2015/> Naloxone may be combined with an opioid (in the same pill) to decrease the risk of misuse.<ref name=AHFS2015/> When given [[Intravenous therapy|intravenously]], naloxone works within two minutes, and when [[Intramuscular injection|injected into a muscle]], it works within five minutes;<ref name=AHFS2015/> it may also be [[Nasal administration|sprayed into the nose]].<ref>{{cite book|last1=Roberts|first1=James R.|title=Roberts and Hedges' clinical procedures in emergency medicine|date=2014|publisher=Elsevier Health Sciences|location=London|isbn=9781455748594|page=476|edition=6|url=https://books.google.com/books?id=slyLreFkHuIC&pg=PA476|deadurl=no|archiveurl=https://web.archive.org/web/20170908140357/https://books.google.com/books?id=slyLreFkHuIC&pg=PA476|archivedate=2017-09-08|df=}}</ref> The effects of naloxone last about half an hour to an hour.<ref>{{cite book|last1=Bosack|first1=Robert|title=Anesthesia Complications in the Dental Office|date=2015|publisher=John Wiley & Sons|isbn=9781118828625|page=191|url=https://books.google.com/books?id=Rn51BwAAQBAJ&pg=PA191|deadurl=no|archiveurl=https://web.archive.org/web/20170908140357/https://books.google.com/books?id=Rn51BwAAQBAJ&pg=PA191|archivedate=2017-09-08|df=}}</ref> Multiple doses may be required, as the duration of action of most opioids is greater than that of naloxone.<ref name=AHFS2015/>

<!-- Side effects and mechanism -->
Administration to opioid-dependent individuals may cause symptoms of [[opioid withdrawal]], including restlessness, agitation, nausea, vomiting, a [[tachycardia|fast heart rate]], and sweating.<ref name=AHFS2015/> To prevent this, small doses every few minutes can be given until the desired effect is reached.<ref name=AHFS2015/> In those with previous heart disease or taking medications that negatively affect the heart, further heart problems have occurred.<ref name=AHFS2015>{{cite web|title=Naloxone Hydrochloride|url=https://www.drugs.com/monograph/naloxone-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|accessdate=Jan 2, 2015|deadurl=no|archiveurl=https://web.archive.org/web/20150102115454/http://www.drugs.com/monograph/naloxone-hydrochloride.html|archivedate=2015-01-02|df=}}</ref> It appears to be safe in pregnancy, after having been given to a limited number of women.<ref name=TGA2014>{{cite web|title=Prescribing medicines in pregnancy database|url=http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw|work=Australian Government|accessdate=22 April 2014|date=3 March 2014|deadurl=no|archiveurl=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm#.U1Yw8Bc3tqw|archivedate=8 April 2014|df=}}</ref> Naloxone is a [[non-selective]] and [[competitive antagonist|competitive]] [[opioid receptor antagonist]].<ref name="NHM-Naloxone pharmacology" /><ref name="Narcan Prescribing Information" /> It works by reversing the depression of the central nervous system and respiratory system caused by opioids.<ref name=AHFS2015/>

<!-- History, society and culture -->
Naloxone was patented in 1961 and approved for opioid overdose by the [[Food and Drug Administration]] in 1971.<ref name="nyti_Jack">{{Cite web| title = Jack Fishman Dies at 83; Saved Many From Overdose| last = Yardley| first = William| work = New York Times| date = 14 December 2013| accessdate = 2015-07-06| url = https://www.nytimes.com/2013/12/15/business/jack-fishman-who-helped-develop-a-drug-to-treat-overdoses-dies-at-83.html?_r=0| deadurl = no| archiveurl = https://web.archive.org/web/20131215103845/http://www.nytimes.com/2013/12/15/business/jack-fishman-who-helped-develop-a-drug-to-treat-overdoses-dies-at-83.html?_r=0| archivedate = 15 December 2013| df = }}</ref> It is on the [[World Health Organization's List of Essential Medicines]], the most effective and safe medicines needed in a health system.<ref name=WHO19th>{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016|df=}}</ref> Naloxone is available as a [[generic medication]].<ref name=AHFS2015/> Its wholesale price in the [[developing world]] is between $0.50 and $5.30 per dose.<ref>{{cite web|title=Naloxone HCL|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=537&searchYear=2014|website=International Drug Price Indicator Guide|accessdate=13 August 2015}}</ref> Vials of naloxone are not very expensive (less than $25) in the United States.<ref>{{cite book|last1=Hamilton|first1=Richard J.|title=Tarascon pocket pharmacopoeia : 2014 classic shirt-pocket edition|date=2013|publisher=Jones & Bartlett Learning|location=Sudbury|isbn=9781284053982|page=174|edition=28|url=https://books.google.com/books?id=y0KFAgAAQBAJ&pg=PA174|deadurl=no|archiveurl=https://web.archive.org/web/20170908140357/https://books.google.com/books?id=y0KFAgAAQBAJ&pg=PA174|archivedate=2017-09-08|df=}}</ref> The price for a package of two [[auto-injector]]s in the US, however, has increased from $690 in 2014 to $4,500 in 2016.<ref name="Gupta">{{cite journal | title =Perspective: The Rising Price of Naloxone — Risks to Efforts to Stem Overdose Deaths | journal =N Engl J Med | date =December 8, 2016 | author = | authors =Ravi Gupta, Nilay D. Shah, and Joseph S. Ross | volume =375 | issue =23 | pages =2213–2215 | url =http://www.nejm.org/doi/full/10.1056/NEJMp1609578 | doi =10.1056/NEJMp1609578 | pmid = | pmc = | deadurl =no | archiveurl =https://web.archive.org/web/20170614201858/http://www.nejm.org/doi/full/10.1056/NEJMp1609578 | archivedate =June 14, 2017 | df = }}</ref> The 2018 price for the [[NHS]] in the United Kingdom is about £5 per dose.<ref name=BNF74>{{cite book|title=British national formulary : BNF 74|date=2017|publisher=British Medical Association|isbn=978-0857112989|page=1260|edition=74}}</ref>
{{TOC limit|3}}

==Medical uses==

===Opioid overdose===
[[File:NaloxoneKit.jpg|thumb|A naloxone kit as distributed in British Columbia, Canada]]
Naloxone is useful both in acute [[opioid overdose]] and in reducing respiratory or mental depression due to opioids.<ref name=AHFS2015/> Whether it is useful in those in [[cardiac arrest]] due to an opioid overdose is unclear.<ref name="special circum 2015">{{cite journal|last1=Lavonas|first1=EJ|last2=Drennan|first2=IR|last3=Gabrielli|first3=A|last4=Heffner|first4=AC|last5=Hoyte|first5=CO|last6=Orkin|first6=AM|last7=Sawyer|first7=KN|last8=Donnino|first8=MW|title=Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.|journal=Circulation|date=3 November 2015|volume=132|issue=18 Suppl 2|pages=S501-18|pmid=26472998|doi=10.1161/cir.0000000000000264}}</ref>

It is included as a part of emergency overdose response kits distributed to [[heroin]] and other opioid drug users and emergency responders. This has been shown to reduce rates of deaths due to overdose.<ref name="pmid16956873">{{cite journal |vauthors=Maxwell S, Bigg D, Stanczykiewicz K, Carlberg-Racich S | title = Prescribing naloxone to actively injecting heroin users: a program to reduce heroin overdose deaths | journal = J Addict Dis | volume = 25 | issue = 3 | pages = 89–96 | year = 2006 | pmid = 16956873 | doi = 10.1300/J069v25n03_11 }}</ref> A prescription for naloxone is recommended if a person is on a high dose of opioid (>100&nbsp;mg of morphine equivalence/day), is prescribed any dose of opioid accompanied by a [[benzodiazepine]], or is suspected or known to use opioids nonmedically.<ref>{{cite journal|author=Lazarus P |title=Project Lazarus, Wilkes County, North Carolina: Policy Briefing Document Prepared for the North Carolina Medical Board in Advance of the Public Hearing Regarding Prescription Naloxone |year=2007|location=Raleigh, NC }}{{page needed|date=February 2014}}{{vs|date=February 2014}}</ref> Prescribing naloxone should be accompanied by standard education that includes preventing, identifying, and responding to an overdose; rescue breathing; and calling emergency services.<ref name="pmid23664112">{{cite journal |vauthors=Bowman S, Eiserman J, Beletsky L, Stancliff S, Bruce RD | title = Reducing the health consequences of opioid addiction in primary care | journal = Am. J. Med. | volume = 126 | issue = 7 | pages = 565–71 |date=July 2013 | pmid = 23664112 | doi = 10.1016/j.amjmed.2012.11.031 }}</ref>

===Preventing opioid abuse===
Naloxone is poorly absorbed when taken by mouth, so it is commonly combined with a number of oral opioid preparations, including [[buprenorphine]] and [[pentazocine]], so that when taken orally, just the opioid has an effect, but if misused by injecting, the naloxone blocks the effect of the opioid.<ref name=AHFS2015/><ref name=Orman2009>{{cite journal|last1=Orman|first1=JS|last2=Keating|first2=GM|title=Buprenorphine/naloxone: a review of its use in the treatment of opioid dependence.|journal=Drugs|date=2009|volume=69|issue=5|pages=577–607|pmid=19368419|doi=10.2165/00003495-200969050-00006}}</ref> This combination is used in an effort to prevent abuse.<ref name=Orman2009/> In Germany, [[tilidine]] is sold in a fixed combination with&nbsp;naloxone.

===Other uses===
Naloxone can be used on infants that were exposed to intrauterine opiates administered to mothers during delivery. However, there is insufficient evidence for the use of naloxone to lower cardiorespiratory and neurological depression in these infants.<ref>{{cite journal|last1=Moe-Byrne|first1=Thirimon|last2=Brown|first2=Jennifer VE|last3=McGuire|first3=William|title=Naloxone for opiate-exposed newborn infants|journal=The Cochrane Library|date=28 February 2013|doi=10.1002/14651858.CD003483.pub2}}</ref> Infants exposed to high concentrations of opiates during pregnancy may have CNS damage in the setting of [[perinatal asphyxia]]. Naloxone has been studied to improve outcomes in this population, however the evidence is currently weak.<ref>{{Cite journal|title=Naloxone for preventing morbidity and mortality in newborn infants of greater than 34 weeks' gestation with suspected perinatal asphyxia |last=McGuire|first=William|last2=Fowlie|first2=Peter W|last3=Evans|first3=David J|date=2004-01-26|journal=The Cochrane Library |publisher=John Wiley & Sons, Ltd|issn=1465-1858|language=en|doi=10.1002/14651858.CD003955.pub2}}</ref><ref>{{cite journal |last1=Moe-Byrne |first1=Thirimon |last2=Brown |first2=Jennifer Valeska Elli |last3=McGuire |first3=William |title=Naloxone for opioid-exposed newborn infants |journal=Cochrane Database of Systematic Reviews |date=12 October 2018 |doi=10.1002/14651858.CD003483.pub3}}</ref>

In people with [[circulatory shock|shock]], including [[septic shock|septic]], cardiogenic, hemorrhagic, or spinal shock, those who received naloxone had improved blood flow. The importance of this is unclear.<ref>{{cite journal|last=Boef|first=B|author2=Poirier V |author3=Gauvin F |author4=Guerguerian AM |author5=Roy C |author6=Farrell CA |author7=Lacroix J |title=Naloxone for shock.|journal=Cochrane Database Syst Rev|date=2003|issue=4|pmid=14584016|doi=10.1002/14651858.CD004443 |pages=CD004443}}</ref>

Naloxone is also experimentally used in the treatment for [[congenital insensitivity to pain with anhidrosis]], an extremely rare disorder (one in 125 million) that renders one unable to feel pain or differentiate temperatures.{{citation needed|date=January 2015}}

Naloxone can also be used as an antidote in overdose of [[clonidine]], a medication that lowers blood pressure.<ref>{{cite journal|last1=Niemann|first1=JT|last2=Getzug|first2=T|last3=Murphy|first3=W|title=Reversal of clonidine toxicity by naloxone.|journal=Annals of Emergency Medicine|date=October 1986|volume=15|issue=10|pages=1229–31|pmid=3752658|doi=10.1016/s0196-0644(86)80874-5}}</ref>

Naloxone can also be used to treat itchiness brought on by opioid use.<ref name=":1">{{Cite web|url=https://www.uptodate.com/contents/naloxone-drug-information?source=search_result&search=naloxone&selectedTitle=1~150#F25732507|title=Naloxone|last=|first=|date=|website=www.uptodate.com|access-date=2017-10-31}}</ref>

===Routes of administration===
Naloxone is most commonly injected [[intravenously]] for fastest action, which usually causes the drug to act within a minute, and lasts up to 45 minutes. It can also be administered via [[intramuscular]], subcutaneous injection, or nasal spray.<ref name=":0">{{Cite web|title = DailyMed - NARCAN- naloxone hydrochloride spray|url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=724df050-5332-4d0a-9a5f-17bf08a547e1|website = dailymed.nlm.nih.gov|access-date = 2016-01-22|deadurl = no|archiveurl = https://web.archive.org/web/20160130063652/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=724df050-5332-4d0a-9a5f-17bf08a547e1|archivedate = 2016-01-30|df = }}</ref> There is a prepackaged nasal spray that does not require assembly and delivers a consistent dose.<ref>{{Cite web|title = FDA Approves Narcan Nasal Spray|url = http://www.jems.com/articles/2015/11/fda-approves-narcan-nasal-spray.html|website = www.jems.com|accessdate = 2015-11-21|deadurl = no|archiveurl = https://web.archive.org/web/20151120184918/http://www.jems.com/articles/2015/11/fda-approves-narcan-nasal-spray.html|archivedate = 2015-11-20|df = }}</ref> It can be repeated if necessary.<ref>{{Cite web|title = Press Announcements - FDA moves quickly to approve easy-to-use nasal spray to treat opioid overdose|url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473505.htm|website = www.fda.gov|access-date = 2016-01-22|language = en|deadurl = no|archiveurl = https://web.archive.org/web/20160115094237/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473505.htm|archivedate = 2016-01-15|df = }} {{PD-notice}}</ref> A non-FDA approved wedge device (nasal atomizer) attached to a syringe may be used to create a mist that delivers the drug to the nasal [[mucosa]].<ref name="pmid15039670">{{cite journal |vauthors=Wolfe TR, Bernstone T | title = Intranasal drug delivery: an alternative to intravenous administration in selected emergency cases | journal = J Emerg Nurs | volume = 30 | issue = 2 | pages = 141–7 |date=April 2004 | pmid = 15039670 | doi = 10.1016/j.jen.2004.01.006 }}</ref> This is useful near facilities where many overdoses occur that already stock injectors.<ref>{{cite web|last1=Fiore|first1=Kristina|title=On-Label Nasal Naloxone in the Works|url=http://www.medpagetoday.com/PublicHealthPolicy/PublicHealth/52118|website=MedPage Today|accessdate=2015-07-20|deadurl=no|archiveurl=https://web.archive.org/web/20150801184056/http://www.medpagetoday.com/PublicHealthPolicy/PublicHealth/52118|archivedate=2015-08-01|df=}}</ref>

If minimal or no response is observed within 2–3 minutes, dosing may be repeated every 2 minutes until the maximum dose of 10&nbsp;mg has been reached. If no response occurs at this time, alternative diagnosis and treatment should be pursued. The effects of naloxone may wear off before those of the opioids, and they may require repeat dosing at a later time. Patients experiencing effects should be monitored for respiratory rate, heart rate, blood pressure, temperature, ABGs and level of consciousness. Those with a greater risk for respiratory depression should be identified prior to administration and watched closely.<ref>{{Cite web|url=https://www.uptodate.com/contents/naloxone-drug-information?source=search_result&search=Naloxone&selectedTitle=1~150#F199434|title=Up To Date: Naloxone Monitoring Parameters|last=|first=|date=|website=Up to Date|archive-url=https://web.archive.org/web/20171117003258/https://www.uptodate.com/contents/naloxone-drug-information?source=search_result&search=Naloxone&selectedTitle=1~150#F199434|archive-date=2017-11-17|access-date=|deadurl=yes|df=}}</ref>

In April 2014, the US [[Food and Drug Administration]] (FDA) approved a hand-held automatic injector naloxone product that is pocket-sized and can be used in nonmedical settings such as in the home.<ref name="special circum 2015" /> It is designed for use by laypersons, including family members and caregivers of opioid users at-risk for an opioid emergency, such as an overdose.<ref name="FDA News Release">{{cite web|last1=FDA News Release|title=FDA approves new hand-held auto-injector to reverse opioid overdose|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm|website=FDA.gov|accessdate=2015-07-20|deadurl=no|archiveurl=https://web.archive.org/web/20150716003000/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm|archivedate=2015-07-16|df=}}</ref> A nasal spray was developed in a partnership between LightLake Therapeutics and the [[National Institute on Drug Abuse]].<ref>{{Cite web|url=https://www.drugabuse.gov/about-nida/noras-blog/2015/11/narcan-nasal-spray-life-saving-science-nida|title=NARCAN Nasal Spray: Life Saving Science at NIDA|last=Volkow|first=Nora|date=18 November 2015|website=DrugAbuse.gov—"Nora's Blog"|archive-url=https://web.archive.org/web/20170226133910/https://www.drugabuse.gov/about-nida/noras-blog/2015/11/narcan-nasal-spray-life-saving-science-nida|archive-date=2017-02-26|dead-url=no|access-date=|df=}}</ref> The approval process was fast-tracked as one initiative to reduce the death toll caused by opiate overdoses. At the time of approval, an estimated 16,000 annual deaths were attributed to prescription opioid overdoses in the US.<ref>{{cite news|title=FDA approves device to combat opioid drug overdose|url=https://www.washingtonpost.com/national/health-science/fda-approves-device-to-combat-opiod-drug-overdose/2014/04/03/35b69cac-bb3e-11e3-96ae-f2c36d2b1245_story.html|accessdate=8 April 2014|newspaper=The Washington Post|date=3 April 2014|author=Brady Dennis|deadurl=no|archiveurl=https://web.archive.org/web/20140407173215/http://www.washingtonpost.com/national/health-science/fda-approves-device-to-combat-opiod-drug-overdose/2014/04/03/35b69cac-bb3e-11e3-96ae-f2c36d2b1245_story.html|archivedate=7 April 2014|df=}}</ref>

Naloxone can be used along with [[oxycodone]] controlled release and may help reduce constipation associated with opioids. Naloxone has low systemic bioavailability when [[Oral administration|taken by mouth]] due to hepatic first pass metabolism, but it does block opioid receptors that are located in the intestine.<ref name="pmid10601678">{{cite journal |vauthors=Meissner W, Schmidt U, Hartmann M, Kath R, Reinhart K | title = Oral naloxone reverses opioid-associated constipation | journal = Pain | volume = 84 | issue = 1 | pages = 105–9 |date=January 2000 | pmid = 10601678 | doi = 10.1016/S0304-3959(99)00185-2 }}</ref>

==Special populations==

===Pregnancy and breastfeeding===
Naloxone is [[pregnancy category]] B or C in the United States.<ref name=AHFS2015/> Studies in rodents given a daily maximum dose of 10&nbsp;mg naloxone showed no harmful effects to the fetus, although human studies are lacking and the drug does cross the [[placenta]], which may lead to the precipitation of withdrawal in the fetus. In this setting, further research is needed before safety can be assured, so naloxone should be used during pregnancy only if it is a medical necessity.<ref>{{cite journal|last=Sobor|first=M |author2=Timar, J. |author3=Riba, P. |author4=Kiraly, KP.|title=Behavioural studies during the gestational-lactation period in morphine treated rats|journal=Neuropsychopharmacol Hung|date=2013|volume=15|issue=4|pages=239–251|pmid=24380965}}</ref>

Whether naloxone is excreted in [[breast milk]] is unknown, however, it is not [[Bioavailability|orally bioavailable]] and therefore is unlikely to affect a [[breastfeeding]] infant.<ref>{{Cite news|url=https://www.drugs.com/breastfeeding/naloxone.html|title=Naloxone use while Breastfeeding {{!}} Drugs.com|work=Drugs.com|access-date=2018-08-15|language=en-US}}</ref>

===Kidney and liver dysfunction===
Currently, no established clinical trials have been conducted in person with insufficient kidney function or liver disease, and as such, these people should be monitored closely if naloxone is clinically indicated.

===Cardiovascular disease===
Naloxone should be used with caution in people with cardiovascular disease as well as those that are currently taking medications that could have adverse effects on the cardiovascular system such as causing [[Hypotension|low blood pressure]], [[pulmonary edema|fluid accumulation in the lungs]] (pulmonary edema), and [[arrhythmia|abnormal heart rhythms]]. There have been reports of abrupt reversals with opioid antagonists leading to pulmonary edema and [[ventricular fibrillation]].<ref>{{Cite web|url=https://www.uptodate.com/contents/naloxone-drug-information?source=search_result&search=naloxone&selectedTitle=1~150#F199443|title=Naloxone: Contraindications|last=|first=|date=|website=Up to Date|access-date=2017-10-31}}</ref>

==Side effects==
Naloxone has little to no effect if opioids are not present. In people with opioids in their system, it may cause increased sweating, nausea, restlessness, trembling, vomiting, flushing, and headache, and has in rare cases been associated with heart rhythm changes, [[seizures]], and [[pulmonary edema]].<ref>{{cite web |url=https://www.drugs.com/sfx/naloxone-side-effects.html |title=Naloxone Side Effects in Detail |website=Drugs.com |accessdate=5 May 2015 |deadurl=no |archiveurl=https://web.archive.org/web/20150507072325/http://www.drugs.com/sfx/naloxone-side-effects.html |archivedate=7 May 2015 |df= }}</ref><ref name="pmid3662194">{{cite journal |vauthors=Schwartz JA, Koenigsberg MD | title = Naloxone-induced pulmonary edema | journal = Ann Emerg Med | volume = 16 | issue = 11 | pages = 1294–6 |date=November 1987 | pmid = 3662194 | doi = 10.1016/S0196-0644(87)80244-5 }}</ref>

Besides the side effects listed above, naloxone also has other adverse events, such as other cardiovascular effects (hypertension, hypotension, tachycardia, ventricular fibrillation, ventricular tachycardia) and central nervous system effects, such as agitation, body pain, brain disease, and coma. In addition to these adverse effects, naloxone is also contraindicated in people with hypersensitivity to naloxone or any of its formulation components.<ref>{{Cite web|url=https://www.uptodate.com/contents/naloxone-drug-information?source=search_result&search=naloxone&selectedTitle=1~150#F199428|title=Naloxone: Drug Information|last=|first=|date=|website=UpToDate|access-date=}}</ref>

Naloxone has been shown to block the action of pain-lowering [[endorphin]]s which the body produces naturally. These endorphins likely operate on the same opioid receptors that naloxone blocks. It is capable of blocking a [[placebo]] pain-lowering response, if the placebo is administered together with a hidden or blind injection of naloxone.<ref name="pmid15820838">{{cite journal|date=February 2005|title=Endogenous opiates and the placebo effect: a meta-analytic review|journal=J Psychosom Res|volume=58|issue=2|pages=115–20|doi=10.1016/j.jpsychores.2004.07.001|pmid=15820838|vauthors=Sauro MD, Greenberg RP}}</ref> Other studies have found that placebo alone can activate the body's μ-opioid endorphin system, delivering pain relief by the same receptor mechanism as morphine.<ref>{{Cite news|url=http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/|title=More Than Just a Sugar Pill: Why the placebo effect is real - Science in the News|date=2016-09-14|work=Science in the News|access-date=2017-11-14|language=en-US}}</ref><ref>{{Cite journal|last=Carvalho|first=Cláudia|last2=Caetano|first2=Joaquim Machado|last3=Cunha|first3=Lidia|last4=Rebouta|first4=Paula|last5=Kaptchuk|first5=Ted J.|last6=Kirsch|first6=Irving|date=December 2016|title=Open-label placebo treatment in chronic low back pain: a randomized controlled trial|journal=Pain|volume=157|issue=12|pages=2766–2772|doi=10.1097/j.pain.0000000000000700|issn=1872-6623|pmc=5113234|pmid=27755279}}</ref>

==Pharmacology==

===Pharmacodynamics===
{| class="wikitable floatright" style="text-align: center;"
|+ Naloxone at opioid receptors
|-
! rowspan="2" | Compound || colspan="3" | [[Binding affinity|Affinities]] ({{abbrlink|K<sub>i</sub>|Inhibitor constant}}) || Ratio || rowspan="2" | Ref
|-
! {{abbrlink|MOR|μ-Opioid receptor}} !! {{abbrlink|DOR|δ-Opioid receptor}} !! {{abbrlink|KOR|κ-Opioid receptor}} !! MOR:DOR:KOR
|-
| Naloxone || 1.1 nM || 16 nM || 12 nM || 1:15:11 || <ref name="pmid2986989">{{cite journal | vauthors = Tam SW | title = (+)-[3H]SKF 10,047, (+)-[3H]ethylketocyclazocine, mu, kappa, delta and phencyclidine binding sites in guinea pig brain membranes | journal = Eur. J. Pharmacol. | volume = 109 | issue = 1 | pages = 33–41 | year = 1985 | pmid = 2986989 | doi = 10.1016/0014-2999(85)90536-9| url = }}</ref>
|-
| (−)-Naloxone || 0.559 nM<br />0.93 nM || 36.5 nM<br />17 nM || 4.91 nM<br />2.3 nM || 1:65:9<br />1:18:2 || <ref name="pmid7562497">{{cite journal |vauthors=Codd EE, Shank RP, Schupsky JJ, Raffa RB | title = Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception | journal = J. Pharmacol. Exp. Ther. | volume = 274 | issue = 3 | pages = 1263–70 |date=September 1995 | pmid = 7562497 | doi = | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7562497}}</ref><br /><ref name="pmid8114680">{{cite journal | vauthors = Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T | title = Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors | journal = Mol. Pharmacol. | volume = 45 | issue = 2 | pages = 330–4 | year = 1994 | pmid = 8114680 | doi = | url = http://molpharm.aspetjournals.org/content/45/2/330.short}}</ref>
|-
| (+)-Naloxone || 3,550 nM<br/>1,000 nM || 122,000 nM<br/>1,000 nM || 8,950 nM<br/>1,000 nM || 1:34:3<br />{{abbr|ND|No data}} || <ref name="pmid7562497" /><br /><ref name="pmid8114680" />
|}

Naloxone is a [[lipophilic]] compound that acts as a [[non-selective]] and [[competitive antagonist|competitive]] [[opioid receptor antagonist]].<ref name="NHM-Naloxone pharmacology">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE | editor = Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 190–191, 287 | edition = 2nd | quote= Products of this research include the discovery of lipophilic, small-molecule opioid receptor antagonists, such as naloxone and naltrexone, which have been critical tools for investigating the physiology and behavioral actions of opiates.&nbsp;... A competitive antagonist of opiate action (naloxone) had been identified in early studies.&nbsp;... Opiate antagonists have clinical utility as well. Naloxone, a nonselective antagonist with a relative affinity of μ > δ > κ, is used to treat heroin and other opiate overdoses.}}</ref><ref name="Narcan Prescribing Information">{{cite web | title = Narcan Prescribing Information | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208411s001lbl.pdf | publisher = Adapt Pharma, Inc. | work = United States Food and Drug Administration | date= January 2017 | accessdate = 3 November 2017 }}</ref> The pharmacologically active isomer of naloxone is (−)-naloxone.<ref name="pmid7562497" /><ref name="Naloxone IUPHAR">{{cite web|title=Naloxone: Summary|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638|website=IUPHAR/BPS Guide to Pharmacology|publisher=International Union of Basic and Clinical Pharmacology|accessdate=15 November 2017|quote=The approved drug naloxone INN-assigned preparation is the (-)-enantiomer.&nbsp;... The (+) isomer is inactive at the opioid receptors. Marketed formulations may contain naloxone hydrochloride}}</ref> Naloxone's [[binding affinity]] is highest for the [[μ-opioid receptor]], then the [[δ-opioid receptor]], and lowest for the [[κ-opioid receptor]];<ref name="NHM-Naloxone pharmacology" /> naloxone has negligible affinity for the [[nociceptin receptor]].<ref name="Opioid receptor family – IUPHAR">{{cite web|title=Opioid receptors: Introduction|url=http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=50|website=IUPHAR/BPS Guide to Pharmacology|publisher=International Union of Basic and Clinical Pharmacology|accessdate=15 November 2017|quote=The opioid antagonist, naloxone, which binds to μ, δ and κ receptors (with differing affinities), does not have significant affinity for the ORL1/LC132 receptor. These studies indicate that, from a pharmacological perspective, there are two major branches in the opioid peptide-N/OFQ receptor family: the main branch comprising the μ, δ and κ receptors, where naloxone acts as an antagonist; and a second branch with the receptor for N/OFQ which has negligible affinity for naloxone.}}</ref>

If naloxone is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs, except the inability for the body to combat pain naturally. In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opiate receptor sites within the CNS (a competitive antagonist, not a direct agonist), thereby preventing the action of both [[endogenous]] and [[xenobiotic]] opiates on these receptors without directly producing any effects itself.<ref name="Daily Med">{{cite web|title=Naloxone Hydrochloride injection, solution|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8535cc84-ad4a-4d67-8480-fb5a2e3406f8|publisher=Daily Med|accessdate=21 April 2014|deadurl=no|archiveurl=https://web.archive.org/web/20140422232959/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8535cc84-ad4a-4d67-8480-fb5a2e3406f8|archivedate=22 April 2014|df=}}</ref>

===Pharmacokinetics===
When administered [[wikt:parenteral|parenterally]] (nonorally or nonrectally, e.g. intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The mean serum half life has been shown to range from 30 to 81 minutes, shorter than the average half life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period. Naloxone is primarily metabolized by the liver. Its major metabolite is naloxone-3-glucuronide, which is excreted in the urine.<ref name="Daily Med"/>

==Chemistry==
Naloxone, also known as N-allylnoroxymorphone or as 17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one, is a [[synthetic compound|synthetic]] [[morphinan]] [[chemical derivative|derivative]] and was derived from [[oxymorphone]] (14-hydroxydihydromorphinone), an opioid analgesic.<ref name="DeanBilsky2009">{{cite book|author1=Reginald Dean|author2=Edward J. Bilsky|author3=S. Stevens Negus|title=Opiate Receptors and Antagonists: From Bench to Clinic|url=https://books.google.com/books?id=zqj2vy6VFUcC&pg=PA514|date=12 March 2009|publisher=Springer Science & Business Media|isbn=978-1-59745-197-0|pages=514–}}</ref><ref name="Nagase2011">{{cite book|author=Hiroshi Nagase|title=Chemistry of Opioids|url=https://books.google.com/books?id=eegLBwAAQBAJ&pg=PA93|date=21 January 2011|publisher=Springer|isbn=978-3-642-18107-8|pages=93–}}</ref><ref name="NIST">http://webbook.nist.gov/cgi/cbook.cgi?ID=C465656</ref> Oxymorphone, in turn, was derived from [[morphine]], an opioid analgesic and [[natural product|naturally occurring]] constituent of the [[opium poppy]].<ref name="SeppalaRose2011">{{cite book|author1=Marvin D Seppala|author2=Mark E. Rose|title=Prescription Painkillers: History, Pharmacology, and Treatment|url=https://books.google.com/books?id=HkXXDQAAQBAJ&pg=PT143|date=25 January 2011|publisher=Hazelden Publishing|isbn=978-1-59285-993-1|pages=143–}}</ref> Naloxone is a [[racemic mixture]] of two [[enantiomer]]s, (–)-naloxone (levonaloxone) and [[(+)-naloxone]] (dextronaloxone), only the former of which is active at opioid receptors.<ref name="Bennett2006">{{cite book|author=Louise A. Bennett|title=New Topics in Substance Abuse Treatment|url=https://books.google.com/books?id=aIDGy72xseMC&pg=PA9|year=2006|publisher=Nova Publishers|isbn=978-1-59454-831-4|pages=9–}}</ref><ref name="Wang2003">{{cite book|author=John Q. Wang|title=Drugs of Abuse: Neurological Reviews and Protocols|url=https://books.google.com/books?id=cuxYNGtzSTIC&pg=PA44|year=2003|publisher=Springer Science & Business Media|isbn=978-1-59259-358-3|pages=44–}}</ref> The drug is a highly [[lipophilic]], allowing it to rapidly penetrate the brain and to achieve a far greater brain to serum ratio than that of morphine.<ref name="DeanBilsky2009" /> Opioid antagonists related to naloxone include [[cyprodime]], [[nalmefene]], [[nalodeine]], [[naloxol]], and [[naltrexone]].<ref name="BruntonChabner2010">{{cite book|author1=Laurence Brunton|author2=Bruce Chabner|author3=Bjorn Knollman|title=Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition|url=https://books.google.com/books?id=bVUfAQAAQBAJ|date=20 December 2010|publisher=McGraw Hill Professional|isbn=978-0-07-162442-8|page=510}}</ref>

The [[chemical half-life]] of naloxone is such that injection and nasal forms have been marketed with 24-month and 18-month shelf-lives, respectively.<ref name=":2">{{Cite press release|title=New Study Indicates Opioid Overdose Reversal Products Chemically Stable Well Past Expiration: Extended Shelf-Life Has Potential for Stockpiles and Communities Date|date=6 November 2018|publisher=American Association of Pharmaceutical Scientists|url=https://higherlogicdownload.s3.amazonaws.com/AAPS/bfc3a388-f31c-452f-88fd-941c2a445a10/UploadedImages/Press_Release_2018/Naloxone_-_AAPS_embargoed_release_Final.pdf|access-date=8 November 2018}}</ref> A 2018 study noted that the nasal and injection forms presented as chemically stable to 36- and 28-months, respectively, which prompted an as yet incomplete five year stability study to be initiated.<ref name=":2" /> This suggests that expired caches of material in community and healthcare settings may still be efficacious substantially beyond their labeled expiration dates.<ref name=":2" />

==History==
Naloxone was patented in 1961 by Mozes J. Lewenstein, [[Jack Fishman]], and the company [[Daiichi Sankyo|Sankyo]].<ref name="nyti_Jack"/> It was approved for opioid abuse treatment in 1971 by the FDA with opioid abuse kits being distributed by many states to medically untrained people beginning in 1996. From the period of 1996 to 2014, the CDC estimates over 26,000 cases of opioid overdose have been reversed using the kits.<ref>{{Cite news|url=http://cordantsolutions.com/the-history-of-naloxone/|title=The History of Naloxone - Cordant Solutions|date=2017-07-05|work=Cordant Solutions|access-date=2017-11-14|language=en-US}}</ref>

==Society and culture==

===Names===
''Naloxone'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, {{abbrlink|DCIT|Denominazione Comune Italiana}}, and {{abbrlink|JAN|Japanese Accepted Name}}, while ''naloxone hydrochloride'' is its {{abbrlink|USAN|United States Adopted Name}} and {{abbrlink|BANM|British Approved Name}}.<ref name="Elks2014">{{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA851|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=851–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA715|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=715–}}</ref><ref name="MortonHall2012">{{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA189|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=189–}}</ref><ref name="Drugs.com">https://www.drugs.com/international/naloxone.html</ref>

The [[patent]] for naloxone has expired; consequently, it is available in [[generic drug|generic medication]]. Brand names of naloxone include Narcan, Nalone, Evzio, Prenoxad Injection, Narcanti, Narcotan, and others.

===Legal status===
In the [[United States]], naloxone is available without a prescription in every state with the exception of Hawaii.<ref>{{Cite news|url=https://cvshealth.com/thought-leadership/naloxone-opioid-overdose-reversal-medication|title=Naloxone Opioid Overdose Reversal Medication {{!}} CVS Health|work=CVS Health|access-date=2018-09-19|language=en}}</ref><ref>{{Cite news|url=https://www.wyomingnews.com/news/local_news/wyoming-s-albertsons-safeway-pharmacies-to-offer-narcan-over-the/article_ca4b259c-08ae-11e8-9f50-17a75174a10d.html|title=Wyoming's Albertsons, Safeway pharmacies to offer Narcan over the counter|last=Eagle|first=Chrissy Suttles, Wyoming Tribune|work=Wyoming Tribune Eagle|access-date=2018-09-19|language=en}}</ref>
However depending on the pharmacy a pharmacist may have to write a prescription or not be able to give naloxone to comply with accounting rules regarding prescription medications as naloxone is still considered a prescription only medication under FDA rules.

While paramedics have carried naloxone for decades, law enforcement officers in many states throughout the country carry naloxone to reverse the effects of heroin overdoses when reaching the location prior to paramedics. As of July 12, 2015, law enforcement departments in 28 states are allowed to or required to carry naloxone to quickly respond to opioid overdoses.<ref>{{cite web |url=http://www.nchrc.org/law-enforcement/us-law-enforcement-who-carry-naloxone/ |title=US Law Enforcement Who Carry Naloxone |website=North Carolina Harm Reduction Coalition |date= |accessdate=12 July 2015 |deadurl=no |archiveurl=https://web.archive.org/web/20150713032125/http://www.nchrc.org/law-enforcement/us-law-enforcement-who-carry-naloxone/ |archivedate=13 July 2015 |df= }}</ref>

In Australia, as of February 1, 2016, naloxone is now available "over the counter" in pharmacies without a prescription.<ref>{{cite web |url=http://www.abc.net.au/triplej/programs/hack/how-painkiller-use-becomes-a-heroin-addiction/7129964 |title=Why the 'heroin antidote' naloxone is now available in pharmacies |publisher=ABC |date=1 February 2016 |accessdate=1 February 2016 |deadurl=no |archiveurl=https://web.archive.org/web/20160204040604/http://www.abc.net.au/triplej/programs/hack/how-painkiller-use-becomes-a-heroin-addiction/7129964 |archivedate=4 February 2016 |df= }}</ref> It comes in single-use filled syringe similar to law enforcement kits.

In Canada, naloxone single-use syringe kits are distributed and available at various clinics and emergency rooms. Alberta Health Services is increasing the distribution points for naloxone kits at all emergency rooms, and various pharmacies and clinics province-wide. Also in [[Alberta]], take-home naloxone kits are available and commonly distributed in most drug treatment or rehabilitation centres, as well as in pharmacies where pharmacists can distribute single-use take-home naloxone kits or prescribe the drug to addicts. All [[Edmonton Police Service]] and [[Calgary Police Service]] patrol cars carry an emergency single-use naloxone syringe kit. Some [[Royal Canadian Mounted Police]] patrol vehicles also carry the drug, occasionally in excess to help distribute naloxone among users and concerned family/friends. Nurses, paramedics, medical technicians, and emergency medical responders can also prescribe and distribute the drug.

Following Alberta Health Services, [[Health Canada]] reviewed the prescription-only status of naloxone, resulting in plans to remove it in 2016, allowing naloxone to be more accessible.<ref>{{cite web |url=http://www.cbc.ca/beta/news/health/naloxone-s-prescription-only-status-to-get-health-canada-review-1.3166867 |title=Naloxone's prescription-only status to get Health Canada review {{!}} CBC News |accessdate=2016-02-05 |deadurl=no |archiveurl=https://web.archive.org/web/20160205205030/http://www.cbc.ca/beta/news/health/naloxone-s-prescription-only-status-to-get-health-canada-review-1.3166867 |archivedate=2016-02-05 |df= }}</ref><ref>{{cite web |url=http://www.health.alberta.ca/health-info/AMH-Naloxone-Take-home.html |title=Fentanyl and the take-home naloxone program Alberta Health |accessdate=2016-02-05 |deadurl=yes |archiveurl=https://web.archive.org/web/20160205142858/http://www.health.alberta.ca/health-info/AMH-Naloxone-Take-home.html |archivedate=2016-02-05 |df= }}</ref> Due to the rising number of drug deaths across the country, Health Canada proposed a change to make naloxone more widely available to Canadians in support of efforts to address the growing number of opioid overdoses.<ref>{{cite news |url=http://news.gc.ca/web/article-en.do?nid=1027679 |title=Health Canada Statement on Change in Federal Prescription Status of Naloxone |website=news.gc.ca |date=January 14, 2016 |accessdate=February 29, 2016 |archive-url=https://web.archive.org/web/20170110031441/http://news.gc.ca/web/article-en.do?nid=1027679 |archive-date=January 10, 2017 |via=[[Wayback Machine]] |deadurl=yes |df= }}</ref> In March 2016, Health Canada did change the prescription status of naloxone, as "pharmacies are now able to proactively give out naloxone to those who might experience or witness an opioid overdose."<ref>{{cite web |url=http://www.hc-sc.gc.ca/dhp-mps/prodpharma/pdl-ord/pdl-ldo-qa-naloxone-qr-eng.php |title=Questions and Answers - Naloxone |website=[[Health Canada]] |date=March 22, 2017 |accessdate=June 12, 2017 |deadurl=no |archiveurl=https://web.archive.org/web/20170908140357/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/pdl-ord/pdl-ldo-qa-naloxone-qr-eng.php |archivedate=September 8, 2017 |df= }}</ref>

===Prehospital access===
Laws in many jurisdictions have been changed in recent years to allow wider distribution of naloxone.<ref>{{cite journal | author = Corey Davis | url = https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf | title = Legal interventions to reduce overdose mortality: Naloxone access and overdose good samaritan laws | journal = Network for Public Health Law | deadurl = no | archiveurl = https://web.archive.org/web/20140903114828/https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf | archivedate = 2014-09-03 | df = }}</ref><ref>{{cite journal | title = Changing Law from Barrier to Facilitator of Opioid Overdose Prevention | journal = Journal of Law, Medicine and Ethics | year = 2013 |vauthors=Davis CS, Webb D, Burris SC }}</ref> Several states have also moved to permit pharmacies to dispense the medication without the person first seeing a physician or other non-pharmacist professional.<ref>Ryan Oftebro, [https://www.krrph.com/kelley-ross-pharmacy-provides-take-home-naloxone-to-prevent-opioid-overdose/ "Kelley-Ross Pharmacy provides Take-Home Naloxone to prevent opioid overdose"] {{webarchive|url=https://web.archive.org/web/20140519022951/https://www.krrph.com/kelley-ross-pharmacy-provides-take-home-naloxone-to-prevent-opioid-overdose/ |date=2014-05-19 }}, ''Kelley-Ross'', August 20, 2013</ref> Over 200 naloxone distribution programs utilize licensed prescribers to distribute the drug, often through the use of standing medication orders <ref name="Beletsky_2009"/><ref>{{cite journal | doi = 10.2139/ssrn.1434381 | title = Stopping an Invisible Epidemic: Legal Issues in the Provision of Naloxone to Prevent Opioid Overdose | journal = SSRN Electronic Journal| year = 2009 |vauthors=Burris SC, Beletsky L, Castagna CA, Coyle C, Crowe C, McLaughlin JM }}</ref> whereby the medication is distributed under the medical authority of a physician or other prescriber (such as a pharmacist under California's [[AB1535]]).

Following the use of the nasal spray device by police officers on Staten Island in New York, an additional 20,000 police officers will begin carrying naloxone in mid-2014. The state's Office of the Attorney General will provide US$1.2 million to supply nearly 20,000 kits. Police Commissioner William Bratton said: "Naloxone gives individuals a second chance to get help".<ref>{{cite news|title=NYPD officers to carry heroin antidote|url=https://www.usatoday.com/story/news/nation-now/2014/05/27/new-york-police-department-naloxone/9630299/|accessdate=30 May 2014|newspaper=USA Today|date=27 May 2014|author=Jessica Durando|deadurl=no|archiveurl=https://web.archive.org/web/20140703123154/http://www.usatoday.com/story/news/nation-now/2014/05/27/new-york-police-department-naloxone/9630299/|archivedate=3 July 2014|df=}}</ref> Emergency Medical Service Providers (EMS) routinely administer naloxone, except where basic Emergency Medical Technicians are prohibited by policy or by state law.<ref>{{cite journal |doi= 10.2105/AJPH.2014.302520 |title= Disparity in Naloxone Administration by Emergency Medical Service Providers and the Burden of Drug Overdose in US Rural Communities | journal = American Journal of Public Health |year= 2015 |vauthors= Faul M, Dailey MW, Sugerman DE, Sasser SM, Levy B, Paulozzi LJ |volume=105 |pages=e26–e32 |pmid=25905856 |pmc=4455515}}</ref>

A survey of US naloxone prescription programs in 2010 revealed that 21 out of 48 programs reported challenges in obtaining naloxone in the months leading up to the survey, due mainly to either cost increases that outstripped allocated funding or the suppliers' inability to fill orders.<ref name="cdc.gov"/> The approximate cost of a 1&nbsp;ml ampoule of naloxone in the US is estimated to be significantly higher than in most Western countries.<ref name="Beletsky_2009"/>

Projects of this type are under way in many North American cities.<ref name="cdc.gov">{{cite journal|title=Community-Based Opioid Overdose Prevention Programs Providing Naloxone — United States, 2010|journal=Centers for Disease Control and Prevention|date=December 2010|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm|pmid=22337174|volume=61|issue=6|pages=101–5|pmc=4378715|deadurl=no|archiveurl=https://web.archive.org/web/20120426204807/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm|archivedate=2012-04-26|df=}}</ref><ref>{{cite web |url=https://www.thestar.com/news/gta/2012/09/09/toronto_naloxone_program_reduces_drug_overdoses_among_addicts.html |title=Toronto naloxone program reduces drug overdoses among addicts |newspaper=The Toronto Star |date=9 September 2012 |author=Karissa Donkin |accessdate=5 May 2015 |deadurl=no |archiveurl=https://web.archive.org/web/20141205045540/http://www.thestar.com/news/gta/2012/09/09/toronto_naloxone_program_reduces_drug_overdoses_among_addicts.html |archivedate=5 December 2014 |df= }}</ref> CDC estimates that the US programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its use have prevented 10,000 opioid overdose deaths.<ref name="cdc.gov"/> Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in [[North Carolina]], and have been replicated in the US military.<ref name="Beletsky_2009">{{cite journal |doi=10.2139/ssrn.1437163|title=Closing Death's Door: Action Steps to Facilitate Emergency Opioid Drug Overdose Reversal in the United States|journal=SSRN Electronic Journal|year=2009|vauthors=Beletsky L, Burris SC, Kral AH }}</ref><ref name="pmid21668761">{{cite journal |vauthors=Albert S, Brason FW, Sanford CK, Dasgupta N, Graham J, Lovette B | title = Project Lazarus: community-based overdose prevention in rural North Carolina | journal = Pain Med | volume = 12 Suppl 2 | issue = | pages = S77–85 |date=June 2011 | pmid = 21668761 | doi = 10.1111/j.1526-4637.2011.01128.x }}</ref> Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise in the US, and effort is increasing to integrate opioid fatality prevention in the overall response to the overdose crisis.<ref name="Beletsky_2012">{{cite journal |vauthors=Beletsky L, Rich JD, Walley AY | title = Prevention of fatal opioid overdose | journal = JAMA | volume = 308 | issue = 18 | pages = 1863–4 |date=November 2012 | pmid = 23150005 | pmc = 3551246 | doi = 10.1001/jama.2012.14205 }}</ref><ref>{{cite journal|author=Lavoie D|title=Naloxone: Drug-Overdose Antidote Is Put In Addicts' Hands|journal=Huffington Post|date=April 2012|url=http://www.huffingtonpost.com/2012/04/26/naloxone-drug-overdose-antidote_n_1456531.html|deadurl=no|archiveurl=https://web.archive.org/web/20120518161613/http://www.huffingtonpost.com/2012/04/26/naloxone-drug-overdose-antidote_n_1456531.html|archivedate=2012-05-18|df=}}</ref><ref name="pmid19602236">{{cite journal |vauthors=Davis CS, Beletsky L | title = Bundling occupational safety with harm reduction information as a feasible method for improving police receptiveness to syringe access programs: evidence from three U.S. cities | journal = Harm Reduct J | volume = 6 | issue = 1| pages = 16 | year = 2009 | pmid = 19602236 | pmc = 2716314 | doi = 10.1186/1477-7517-6-16 }}</ref><ref>{{cite web|title=2013 National drug control strategy|year=2013|url=http://www.whitehouse.gov//sites/default/files/ondcp/policy-and-research/ndcs_2013.pdf|archiveurl=https://web.archive.org/web/20130506222525/http://www.whitehouse.gov/sites/default/files/ondcp/policy-and-research/ndcs_2013.pdf|archive-date=6 May 2013|deadurl=no|df=}}</ref>

Pilot projects were also started in [[Scotland]] in 2006. Also in the UK, in December 2008, the Welsh Assembly government announced its intention to establish demonstration sites for take-home naloxone.<ref>{{cite web|url=http://www.ihra.net/files/2010/08/26/Danny_Morris.pdf|title=IHRA 21st International Conference Liverpool, 26th April 2010 - Introducing 'take home' Naloxone in Wales|accessdate=9 March 2011|deadurl=no|archiveurl=https://web.archive.org/web/20110720062721/http://www.ihra.net/files/2010/08/26/Danny_Morris.pdf|archivedate=20 July 2011|df=}}</ref>

As of February 2016, Pharmacies across [[Alberta]] and some other Canadian jurisdictions are allowed to distribute take-home naloxone kits. Additionally, the Minister of Health issued an order to change basic life support provider's medical scope, within EMS, to administer naloxone in the event of a suspected narcotic overdose. These are part of the government's plan to tackle a growing [[fentanyl]] drug crisis.<ref name="cbc.ca">[http://www.cbc.ca/news/canada/calgary/naloxone-kits-fentanyl-overdose-province-1.3451860 Naloxone kits now available at drug stores as province battles fentanyl crisis - Injection drug can temporarily reverse overdoses] {{webarchive|url=https://web.archive.org/web/20160304141621/http://www.cbc.ca/news/canada/calgary/naloxone-kits-fentanyl-overdose-province-1.3451860 |date=2016-03-04 }}. Retrieved 29 February 2016.</ref>

===Identification===
The [[CAS number]] of naloxone is 465-65-6; the anhydrous [[hydrochloride]] [[salt]] has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water, hydrochloride dihydrate, has CAS 51481-60-8.

===Media===
The 2013 documentary film ''Reach for Me: Fighting to End the American Drug Overdose Epidemic'' interviews people involved in naloxone programs aiming to make naloxone available to opioid users and people with [[chronic pain]].<ref>[http://reach4me.org/ Reach for Me: Fighting to End the American Drug Overdose Epidemic] {{webarchive|url=https://web.archive.org/web/20141217004049/http://reach4me.org/ |date=2014-12-17 }}</ref>

==See also==
* [[Oxycodone/naloxone]]

==References==
{{Reflist}}

==External links==
* [http://www.anypositivechange.org/NALOXONE/ Chicago Recovery Alliance's naloxone distribution project]
* [http://www.inchem.org/documents/antidote/antidote/ant01.htm Report on Naloxone and other opiate antidotes], by the International Programme on Chemical Safety
* [https://www.samhsa.gov/medication-assisted-treatment/treatment/naloxone What Is Naloxone? via Substance Abuse and Mental Health Services Administration| SAMHSA]
* [http://www.pdaps.org/datasets/laws-regulating-administration-of-naloxone-1501695139 Naloxone Overdose Prevention Laws | PDAPS.org]
{{Antidotes}}
{{Opioid receptor modulators}}
{{Sigma receptor modulators}}

[[Category:Alcohols]]
[[Category:Allyl compounds]]
[[Category:Antidotes]]
[[Category:Chemical substances for emergency medicine]]
[[Category:GABAA receptor negative allosteric modulators]]
[[Category:Kappa antagonists]]
[[Category:Ketones]]
[[Category:Morphinans]]
[[Category:Opioid antagonists]]
[[Category:Phenol ethers]]
[[Category:Sigma antagonists]]
[[Category:World Health Organization essential medicines]]
[[Category:RTT]]

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Revision as of 19:53, 18 November 2018

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