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Revision as of 11:44, 22 July 2011 edit86.30.243.179 (talk)No edit summary← Previous edit Latest revision as of 06:27, 22 December 2024 edit undoGraywalls (talk | contribs)Extended confirmed users, Pending changes reviewers26,682 edits Undid revision 1264495444 by Graywalls (talk)Tag: Undo 
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{{Short description|Opioid receptor antagonist}}
{{Drugbox| Verifiedfields = changed
{{Distinguish|Naltrexone|Naloxegol}}
{{more medical citations needed|date=September 2023}}
{{Use dmy dates|date=August 2023}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed | Watchedfields = changed
| verifiedrevid = 401609362 | verifiedrevid = 440816974
| image = Naloxone.svg
|IUPAC_name = (1''S'',5''R'',13''R'',17''S'')- 10,17-dihydroxy- 4-(prop-2-en-1-yl)- 12-oxa- 4-azapentacyclo octadeca- 7(18),8,10-trien- 14-one
| width = 225
|synonyms=<small>17-allyl- 4,5α-epoxy- 3,14-dihydroxymorphinan- 6-one</small>
| alt =
| image=Naloxone.svg
| image2=Naloxone-3D-balls.png | image2 = Naloxone-based-on-xtal-3D-bs-17.png
| width2 = 250
| CASNo_Ref = {{cascite|correct|CAS}}
| alt2 =
| caption =
| USAN = naloxone hydrochloride

<!-- Clinical data -->| pronounce =
| tradename = Narcan, others
| Drugs.com = {{drugs.com|monograph|naloxone-hydrochloride}}
| MedlinePlus = a612022
| DailyMedID = Naloxone
| pregnancy_AU = B1
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Naloxone Use During Pregnancy | website=Drugs.com | date=2 September 2019 | url=https://www.drugs.com/pregnancy/naloxone.html | access-date=13 May 2020 | archive-date=25 April 2020 | archive-url=https://web.archive.org/web/20200425111541/https://www.drugs.com/pregnancy/naloxone.html | url-status=live }}</ref>
| pregnancy_category =
| routes_of_administration = ], ], ]
| class = ]
| ATC_prefix = A06
| ATC_suffix = AH04
| ATC_supplemental = <br />{{ATC|V03|AB15}}

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = /&nbsp;S3 (Pharmacist Only Medicine)<ref name="doi 10.5694/mja15.01181" />
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = OTC
| legal_CA_comment = <ref>{{cite web |title=Frequently Asked Questions: Access to naloxone in Canada (including Narcan Nasal Spray) |url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/announcements/narcan-nasal-spray-frequently-asked-questions.html |website=] |date=6 July 2016 |access-date=16 August 2021 |archive-date=16 August 2021 |archive-url=https://web.archive.org/web/20210816123952/https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/announcements/narcan-nasal-spray-frequently-asked-questions.html |url-status=live }}</ref>
| legal_DE = Anlage 1
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Naloxone 400 micrograms/ml solution for Injection/Infusion – Summary of Product Characteristics (SmPC) | website=(emc) | date=6 February 2019 | url=https://www.medicines.org.uk/emc/product/6344/smpc | access-date=13 May 2020 | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804145336/https://www.medicines.org.uk/emc/product/6344/smpc | url-status=live }}</ref>
| legal_US = OTC
| legal_US_comment = /&nbsp;Rx-only<ref name="Narcan FDA label"/><ref name="Evzio FDA label">{{cite web | title=Evzio- naloxone hydrochloride injection, solution | website=DailyMed | date=1 February 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5fbe8d17-a72f-406d-a736-48e61620f9d8 | access-date=5 October 2020 | archive-date=8 October 2020 | archive-url=https://web.archive.org/web/20201008231037/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5fbe8d17-a72f-406d-a736-48e61620f9d8 | url-status=live }}</ref><ref name="Zimhi FDA label">{{cite web | title=Zimhi- naloxone hydrochloride injection, solution | website=DailyMed | date=29 September 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e49022-9172-4da3-ba83-5995cacca9fb | access-date=7 January 2023 | archive-date=7 January 2023 | archive-url=https://web.archive.org/web/20230107044215/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52e49022-9172-4da3-ba83-5995cacca9fb | url-status=live }}</ref><ref name="Kloxxado FDA label" /><ref>{{cite web | title=Narcan- naloxone hydrochloride nasal spray | website=DailyMed | date=8 August 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0ebc83d-2892-40de-bc0a-775ce90b30db | access-date=5 September 2024}}</ref><ref name="Rivive FDA label">{{cite web | title=Rivive- naloxone hydrochloride spray | website=DailyMed | date=10 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1c4f1b9d-1c70-4666-a90e-2f5d2c670d4d | access-date=5 September 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only

<!-- Pharmacokinetic data -->| bioavailability = 2% (], 90% absorption but high ])<br />43–54% (intranasal)<br />98% (intramuscular, subcutaneous)<ref>{{cite journal | vauthors = Ryan SA, Dunne RB | title = Pharmacokinetic properties of intranasal and injectable formulations of naloxone for community use: a systematic review | journal = Pain Management | volume = 8 | issue = 3 | pages = 231–245 | date = May 2018 | pmid = 29683378 | doi = 10.2217/pmt-2017-0060 | doi-access = free | title-link = doi }}</ref><ref name=AHFS2015/>
| protein_bound =
| metabolism = ]
| metabolites =
| onset = {{abbrlink|IV|intravenous injection}}: 2 min, <br>{{abbrlink|IM|intramuscular injection}}: 5 min<ref name=AHFS2015/>
| elimination_half-life = 1–1.5 h
| duration_of_action = {{abbrlink|IN|Intranasal}}: 30–90 min <br>{{abbrlink|IV|Intravenous}}: 45 min <br>{{abbrlink|IM|Intramuscular}}: 30–120 min
| excretion = ], ]

<!-- Identifiers -->| index2_label = as HCl
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 465-65-6
| CAS_supplemental =
| 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_Ref = {{fdacite|correct|FDA}}
| UNII = 36B82AMQ7N | UNII = 36B82AMQ7N
| KEGG_Ref = {{keggcite|correct|kegg}}
| InChI = 1/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
| KEGG = D08249
| InChIKey = UZHSEJADLWPNLE-GRGSLBFTBH
| KEGG2_Ref = {{keggcite|correct|kegg}}
| smiles = O=C45Oc1c2c(ccc1O)C3N(CC253(O)CC4)C\C=C
| KEGG2 = D01340
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 7459
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 80
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = EN-1530; ''N''-Allylnoroxymorphone; 17-Allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one

<!-- Chemical and physical data -->| IUPAC_name = (4''R'',4a''S'',7a''R'',12b''S'')-4a,9-dihydroxy-3-(prop-2-en-1-yl)-2,3,4,4a,5,6-hexahydro-1''H''-4,12-methanobenzofuranoisoquinolin-7(7a''H'')-one
| C = 19
| H = 21
| N = 1
| O = 4
| SMILES = O=C12OC3=C(O)C=CC4=C32(5(CC1)O)CCN(CC=C)5C4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | 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 | 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
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = UZHSEJADLWPNLE-GRGSLBFTSA-N | StdInChIKey = UZHSEJADLWPNLE-GRGSLBFTSA-N
| CAS_number=465-65-6
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 80
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4447644
| ATC_prefix=V03
| ATC_suffix=AB15
| PubChem = 5284596
| DrugBank=DB01183
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D08249
| C=19 | H=21 | N=1 | O=4
| molecular_weight = 327.37 g/mol
| bioavailability= 2% (90% absorption but high ])
| metabolism = ]
| elimination_half-life=1-1.5 h
| excretion = Urine, Biliary
| pregnancy_category = B (]) <br /> B1 (])
| legal_AU = S4
| routes_of_administration= ], ]
}} }}
'''Naloxone''' is a an ] antagonist drug developed by Sankyo in the 1960s<ref>US Patent 3254088 - Morphine Derivative</ref>. Naloxone is a ] used to counter the effects of ] ], for example ] or ] overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory system. Naloxone is also experimentally used in the treatment for ] (CIPA), an extremely rare disorder (1 in 125 million) that renders one unable to feel pain. It is marketed under various trademarks including '''Narcan''', '''Nalone''', and '''Narcanti''', and has sometimes been mistakenly called "naltrexate." It is not to be confused with ], an ] ] with qualitatively different effects, used for dependence treatment rather than emergency overdose treatment.


<!-- Medical uses -->
==Pharmacodynamics==
'''Naloxone''', sold under the brand name '''Narcan''' among others, is an ], a medication used to reverse or reduce the effects of ].<ref name="AHFS2015" /> For example, it is used to restore breathing after an ].<ref name="AHFS2015" /> Effects begin within two minutes when given ], five minutes when ],<ref name="AHFS2015" /> and ten minutes as a ].<ref>{{cite journal | vauthors = McDonald R, Lorch U, Woodward J, Bosse B, Dooner H, Mundin G, Smith K, Strang J | display-authors = 6 | title = Pharmacokinetics of concentrated naloxone nasal spray for opioid overdose reversal: Phase I healthy volunteer study | journal = Addiction | volume = 113 | issue = 3 | pages = 484–493 | date = March 2018 | pmid = 29143400 | pmc = 5836974 | doi = 10.1111/add.14033 }}</ref> Naloxone blocks the effects of opioids for 30 to 90 minutes.<ref>{{cite web|date=1 June 2021|title=Naloxone DrugFacts|url=https://www.drugabuse.gov/publications/drugfacts/naloxone|url-status=live|access-date=5 January 2022|website=National Institute on Drug Abuse|archive-date=6 January 2022|archive-url=https://web.archive.org/web/20220106000109/https://www.drugabuse.gov/publications/drugfacts/naloxone}}</ref>
Naloxone has an extremely high affinity for ] in the ]. Naloxone is a μ-opioid receptor ], and its rapid blockade of those receptors often produces rapid onset of ] symptoms. Naloxone also has an antagonist action, though with a lower affinity, at ] and ].

Administration to opioid-dependent individuals may cause symptoms of ], including restlessness, agitation, nausea, vomiting, a ], 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|access-date=2 January 2015|url-status=live|archive-url=https://web.archive.org/web/20150102115454/http://www.drugs.com/monograph/naloxone-hydrochloride.html|archive-date=2 January 2015}}</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|work=Australian Government|access-date=22 April 2014|date=3 March 2014|url-status=live|archive-url=https://web.archive.org/web/20140408040902/http://www.tga.gov.au/hp/medicines-pregnancy.htm|archive-date=8 April 2014}}</ref> Naloxone is a ] and ] ].<ref name="Narcan FDA label"/><ref name="NHM-Naloxone pharmacology"/> It reverses 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 in the United States in 1971.<ref name="nyti_Jack">{{cite web | title = Jack Fishman Dies at 83; Saved Many From Overdose| vauthors = Yardley W | work = ]| date = 14 December 2013| access-date = 6 July 2015| url = https://www.nytimes.com/2013/12/15/business/jack-fishman-who-helped-develop-a-drug-to-treat-overdoses-dies-at-83.html| url-status = live| archive-url = 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| archive-date = 15 December 2013}}</ref><ref>{{cite patent |country=US |number=3493657 |status=patent |title=Therapeutic compositions of n-allyl-14-hydroxy - dihydronormorphinane and morphine |pubdate=1970-02-03 |gdate=1970-02-03 |fdate=1964-01-23 |pridate=1961-03-14 |invent1=Jack Fishman |invent2=Mozes Juda Lewenstein |assign1=Mozes Juda Lewenstein |url=https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=19700203&CC=US&NR=3493657A&KC=A }} {{Webarchive|url=https://web.archive.org/web/20221207094723/https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=19700203&CC=US&NR=3493657A&KC=A |date=7 December 2022 }}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>

{{TOC limit|3}}

==Medical uses==

===Opioid overdose===
]

Naloxone is useful in treating both acute ] and respiratory or mental depression due to opioids.<ref name="AHFS2015"/> Whether it is useful in those in ] due to an opioid overdose is unclear.<ref name="special circum 2015">{{cite journal | vauthors = Lavonas EJ, Drennan IR, Gabrielli A, Heffner AC, Hoyte CO, Orkin AM, Sawyer KN, Donnino MW | display-authors = 6 | title = Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care | journal = Circulation | volume = 132 | issue = 18 Suppl 2 | pages = S501–S518 | date = November 2015 | pmid = 26472998 | doi = 10.1161/cir.0000000000000264 | doi-access = free | title-link = doi }}</ref>

It is included as a part of emergency overdose response kits distributed to ] and other opioid drug users, and to 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 = Journal of Addictive Diseases | volume = 25 | issue = 3 | pages = 89–96 | year = 2006 | pmid = 16956873 | doi = 10.1300/J069v25n03_11 | s2cid = 17246459 }}</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 ], or is suspected or known to use opioids nonmedically.<ref>{{cite web |title=Project Lazarus, Wilkes County, North Carolina |work=Policy Briefing Document Prepared for the North Carolina Medical Board in Advance of the Public Hearing Regarding Prescription Naloxone |year=2007 |location=Raleigh, NC |url=http://intranasal.net/Peer%20Reviewed%20literature/Project%20Lazarus,%20North%20Carolina%20IN%20Naloxone%202007.pdf |access-date=20 March 2022 |archive-date=26 May 2022 |archive-url=https://web.archive.org/web/20220526182242/http://intranasal.net/Peer%20Reviewed%20literature/Project%20Lazarus,%20North%20Carolina%20IN%20Naloxone%202007.pdf |url-status=live }}{{page needed|date=February 2014}}{{verify source|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 = The American Journal of Medicine | volume = 126 | issue = 7 | pages = 565–571 | date = July 2013 | pmid = 23664112 | doi = 10.1016/j.amjmed.2012.11.031 }}</ref>

Distribution of naloxone to individuals likely to encounter people who overdose is one aspect of ] strategies.<ref>{{cite book | veditors = Marlatt GA, Larimer ME, Witkiewitz K | date = 2011 | title = Harm reduction: Pragmatic strategies for managing high-risk behaviors. | edition = 2nd | location = New York | publisher = Guilford Press | isbn = 978-1-4625-0256-1 }}</ref>

However, with opioids that have longer half-lives, respiratory depression returns after naloxone has worn off; therefore, adequate dosing and continuous monitoring may be necessary.<ref>{{cite journal | vauthors = van Dorp E, Yassen A, Dahan A | title = Naloxone treatment in opioid addiction: the risks and benefits | journal = Expert Opinion on Drug Safety | volume = 6 | issue = 2 | pages = 125–132 | date = March 2007 | pmid = 17367258 | doi = 10.1517/14740338.6.2.125 | s2cid = 11650530 }}</ref>

===Clonidine overdose===
Naloxone can also be used as an antidote in an overdose of ], a medication that lowers blood pressure.<ref>{{cite journal | vauthors = Niemann JT, Getzug T, Murphy W | title = Reversal of clonidine toxicity by naloxone | journal = Annals of Emergency Medicine | volume = 15 | issue = 10 | pages = 1229–1231 | date = October 1986 | pmid = 3752658 | doi = 10.1016/s0196-0644(86)80874-5 }}</ref> Clonidine overdoses are of special relevance for children, in whom even small doses can cause significant harm.<ref name="Ahmad et al 2015 Review">{{cite journal | vauthors = Ahmad SA, Scolnik D, Snehal V, Glatstein M | title = Use of naloxone for clonidine intoxication in the pediatric age group: case report and review of the literature | journal = American Journal of Therapeutics | volume = 22 | issue = 1 | pages = e14–e16 | date = 2015 | pmid = 23782760 | doi = 10.1097/MJT.0b013e318293b0e8 }}</ref> However, there is controversy regarding naloxone's efficacy in treating the symptoms of clonidine overdose, namely ], ], and ].<ref name="Ahmad et al 2015 Review"/> Case reports that used doses of 0.1{{nbsp}}mg/kg (maximum of 2{{nbsp}}mg/dose) repeated every 1–2 minutes (10{{nbsp}}mg total dose) have shown inconsistent benefit.<ref name="Ahmad et al 2015 Review"/> As the doses used throughout the literature vary, it is difficult to form a conclusion regarding the benefit of naloxone in this setting.<ref name="Seger DL Review">{{cite journal | vauthors = Seger DL | title = Clonidine toxicity revisited | journal = Journal of Toxicology. Clinical Toxicology | volume = 40 | issue = 2 | pages = 145–155 | date = 2002 | pmid = 12126186 | doi = 10.1081/CLT-120004402 | s2cid = 2730597 }}</ref> The mechanism for naloxone's proposed benefit in clonidine overdose is unclear. Still, it has been suggested that endogenous opioid receptors mediate the ] in the brain and elsewhere in the body.<ref name="Seger DL Review"/>

===Preventing recreational opioid use===
Naloxone is poorly absorbed when taken orally or sublingually, so it is often combined with several oral or sublingual opioid preparations, including ] and ], so that when swallowed or taken sublingually, only the non-naloxone opioid has an effect.<ref name="AHFS2015"/><ref name="Orman2009">{{cite journal | vauthors = Orman JS, Keating GM | title = Buprenorphine/naloxone: a review of its use in the treatment of opioid dependence | journal = Drugs | volume = 69 | issue = 5 | pages = 577–607 | date = 2009 | pmid = 19368419 | doi = 10.2165/00003495-200969050-00006 | s2cid = 209147406 }}</ref> However, if the combination is injected (such as by dissolving a pill or sublingual strip in water), the naloxone is believed to block the effect of the other opioid.<ref name="AHFS2015"/><ref name="Orman2009"/> This combination is used to prevent non-medical use.<ref name="Orman2009"/>

However, ]'s clinical guidelines state that if the combination of buprenorphine and naloxone is injected by a regular user of buprenorphine or buprenorphine/naloxone, then the buprenorphine would still produce an agonist effect but the naloxone would fail to produce an antagonist effect. This is because the amount of naloxone that would be required to block the buprenorphine after injection is much larger than the amount that is contained in buprenorphine/naloxone (Suboxone) pills and strips.<ref name="Guidelines SAMHSA"/> If someone who is not physically dependent on opioids were to inject the buprenorphine/naloxone combination, then the effects of the buprenorphine may at most be slightly lessened, but the individual would still be expected to experience euphoric effects.<ref name="Guidelines SAMHSA">{{cite book | vauthors=((Center for Substance Abuse Treatment)) | title=Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction | series=SAMHSA/CSAT Treatment Improvement Protocols | page=23| publisher=U.S. ] (SAMHSA) | date=2004 | url=https://www.ncbi.nlm.nih.gov/books/NBK64245/ | pmid=22514846 }}</ref>

===Other uses===

A 2003 meta-analysis of existing research showed naloxone to improve blood flow in patients with ], including ], cardiogenic, hemorrhagic, or spinal shock, but could not determine if this reduced patient deaths.<ref>{{cite journal | vauthors = Boeuf B, Poirier V, Gauvin F, Guerguerian AM, Roy C, Farrell CA, Lacroix J | title = Naloxone for shock | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD004443 | date = 2003 | volume = 2010 | pmid = 14584016 | doi = 10.1002/14651858.CD004443 | pmc = 9036847 }}</ref>

===Special populations===

====Pregnancy and breastfeeding====

Whether naloxone is excreted in ] is unknown, however, it is not ] and therefore is unlikely to affect a ] infant.<ref>{{cite news|url=https://www.drugs.com/breastfeeding/naloxone.html|title=Naloxone use while Breastfeeding|work=Drugs.com|access-date=15 August 2018|archive-date=2 November 2020|archive-url=https://web.archive.org/web/20201102082637/https://www.drugs.com/breastfeeding/naloxone.html|url-status=live}}</ref>

====Children====
Naloxone can be used on infants who 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 name="Naloxone for opioid-exposed newborn">{{cite journal | vauthors = Moe-Byrne T, Brown JV, McGuire W | title = Naloxone for opioid-exposed newborn infants | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 10 | pages = CD003483 | date = October 2018 | pmid = 30311212 | pmc = 6517169 | doi = 10.1002/14651858.CD003483.pub3 }}</ref> Infants exposed to high concentrations of opiates during pregnancy may have CNS damage in the setting of ]. Naloxone has been studied to improve outcomes in this population, however the evidence is currently weak.<ref>{{cite journal | vauthors = McGuire W, Fowlie PW, Evans DJ | title = Naloxone for preventing morbidity and mortality in newborn infants of greater than 34 weeks gestation with suspected perinatal asphyxia | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003955 | date = 26 January 2004 | volume = 2010 | pmid = 14974047 | pmc = 6485479 | doi = 10.1002/14651858.CD003955.pub2 | publisher = John Wiley & Sons, Ltd }}</ref><ref name="Naloxone for opioid-exposed newborn"/>

Intravenous, intramuscular, or subcutaneous administration of naloxone can be given to children and neonates to reverse opiate effects. The ] recommends only intravenous administration as the other two forms can cause unpredictable absorption. After a dose is given, the child should be monitored for at least 24 hours. For children with low blood pressure due to ], naloxone safety and effectiveness are not established.<ref>{{cite web|url=https://www.rxlist.com/narcan-drug.htm|title=Narcan (Naloxone Hydrochloride Injection): Side Effects, Interactions, Warning, Dosage & Uses|website=RxList|access-date=24 October 2019|archive-date=11 November 2020|archive-url=https://web.archive.org/web/20201111191403/https://www.rxlist.com/narcan-drug.htm|url-status=live}}</ref>

====Geriatric use====
For patients 65 years and older, it is unclear if there is a difference in response. However, older people often have decreased liver and kidney function which may lead to an increased level of naloxone in their body.<ref name="Narcan FDA label"/>

=== Available forms ===

====Intravenous====
In hospital settings, naloxone is injected ], with an onset of 1–2 minutes and a duration of up to 45 minutes.<ref name="Lexicomp. 2013">{{cite book |title=Drug information handbook for advanced practice nursing: a comprehensive resource for nurse practitioners, nurse midwives, and clinical specialists, including selected disease management guidelines. |date=2013|publisher=Lexicomp|isbn=978-1591953234|oclc=827841946}}</ref>

====Intramuscular or subcutaneous====
Naloxone can also be administered via ] or ]. The onset of naloxone provided through this route is 2 to 5 minutes with a duration of around 30–120min.<ref>Naloxone for Treatment of Opioid Overdose Oct. 2016</ref> Naloxone administered intramuscularly are provided through pre-filled syringes, vials, and auto-injector. A hand-held auto-injector is pocket-sized and can be used in non-medical 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 press release |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm|title=FDA approves new hand-held auto-injector to reverse opioid overdose |publisher = U.S. ] (FDA) |archive-url= https://web.archive.org/web/20150716003000/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm|archive-date=16 July 2015|access-date=20 July 2015|url-status=dead}}</ref> According to the FDA's ] Directory, a generic version of the auto-injector began to be marketed at the end of 2019.<ref>{{cite web|url=https://ndclist.com/ndc/72853-051/package/72853-051-02|title=NDC 72853-051-02 Naloxone Hydrochloride Auto-injector|website=NDClist.com|access-date=21 March 2020|archive-date=21 March 2020|archive-url=https://web.archive.org/web/20200321212308/https://ndclist.com/ndc/72853-051/package/72853-051-02|url-status=dead}}</ref>

====Intranasal====
Narcan nasal spray was approved in the US in 2015 and is the first FDA-approved nasal spray for emergency treatment or suspected overdose.<ref name="FDA PR 20190419">{{cite press release|url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-naloxone-nasal-spray-treat-opioid-overdose|title=FDA approves first generic naloxone nasal spray to treat opioid overdose|date=11 September 2019|publisher=U.S. ] (FDA)|access-date=23 October 2019|archive-date=14 September 2019|archive-url=https://web.archive.org/web/20190914122901/https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-naloxone-nasal-spray-treat-opioid-overdose|url-status=live}}</ref><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|access-date = 21 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151120184918/http://www.jems.com/articles/2015/11/fda-approves-narcan-nasal-spray.html|archive-date = 20 November 2015}}</ref> It was developed in a partnership between LightLake Therapeutics and the ].<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| vauthors = Volkow N |date=18 November 2015|website=] (NIDA) |url-status=live|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=26 February 2017}}</ref> The approval process was fast-tracked.<ref>{{cite news|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|title=FDA approves device to combat opioid drug overdose| vauthors = Dennis B |date=3 April 2014|newspaper=]|access-date=8 April 2014|url-status=live|archive-url=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|archive-date=7 April 2014}}</ref> A generic version of the nasal spray was approved in the United States in 2019, though did not come to market until 2021.<ref name="FDA PR 20190419" /><ref name="Teva Pharmaceuticals_2021" />

In 2021, the FDA approved Kloxxado, an 8{{nbsp}}mg dose of intranasal naloxone developed by ].<ref>{{cite press release |date=11 May 2021 |title=FDA Approves Higher Dosage of Naloxone Nasal Spray to Treat Opioid Overdose |url=https://www.fda.gov/news-events/press-announcements/fda-approves-higher-dosage-naloxone-nasal-spray-treat-opioid-overdose |access-date=21 September 2022 |publisher=U.S. ] (FDA) |archive-date=1 September 2022 |archive-url=https://web.archive.org/web/20220901084121/https://www.fda.gov/news-events/press-announcements/fda-approves-higher-dosage-naloxone-nasal-spray-treat-opioid-overdose |url-status=live }}</ref> Citing the frequent need for multiple 4{{nbsp}}mg doses of Narcan to successfully reverse overdose, packs of Kloxxado Nasal Spray contain two pre-packaged nasal spray devices, each containing 8{{nbsp}}mg of naloxone.<ref>{{cite journal | vauthors = Abdelal R, Raja Banerjee A, Carlberg-Racich S, Darwaza N, Ito D, Shoaff J, Epstein J | title = Real-world study of multiple naloxone administration for opioid overdose reversal among bystanders | journal = Harm Reduction Journal | volume = 19 | issue = 1 | pages = 49 | date = May 2022 | pmid = 35596213 | pmc = 9122081 | doi = 10.1186/s12954-022-00627-3 | doi-access = free }}</ref><ref name="Kloxxado FDA label">{{cite web | title=Kloxxado- naloxone hcl spray | website=DailyMed | date=10 May 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebf0f833-c1c0-487c-8f29-01fa8c61b6cb | access-date=7 January 2023 | archive-date=7 January 2023 | archive-url=https://web.archive.org/web/20230107044215/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebf0f833-c1c0-487c-8f29-01fa8c61b6cb | url-status=live }}</ref>

However, a wedge device (nasal atomizer) can also be attached to a syringe that may also be used to create a mist to deliver the drug to the nasal{{nbsp}}].<ref name="pmid15039670">{{cite journal | vauthors = Wolfe TR, Bernstone T | title = Intranasal drug delivery: an alternative to intravenous administration in selected emergency cases | journal = Journal of Emergency Nursing | volume = 30 | issue = 2 | pages = 141–147 | 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| vauthors = Fiore K |title=On-Label Nasal Naloxone in the Works|url=http://www.medpagetoday.com/PublicHealthPolicy/PublicHealth/52118|website=MedPage Today|access-date=20 July 2015|url-status=live|archive-url=https://web.archive.org/web/20150801184056/http://www.medpagetoday.com/PublicHealthPolicy/PublicHealth/52118|archive-date=1 August 2015|date=13 June 2015}}</ref>
]

==Side effects==

Administration of naloxone to somebody who has used opioids may cause rapid-onset ].<ref name=britch>{{cite journal |vauthors=Britch SC, Walsh SL |title=Treatment of opioid overdose: current approaches and recent advances |journal=Psychopharmacology (Berl) |volume=239 |issue=7 |pages=2063–2081 |date=July 2022 |pmid=35385972 |pmc=8986509 |doi=10.1007/s00213-022-06125-5 |type=Review}}</ref>

Naloxone has little to no effect if opioids are not present.<ref>{{Cite web |date=2023-08-29 |title=Opioid overdose |url=https://www.who.int/news-room/fact-sheets/detail/opioid-overdose |access-date=2023-11-17 |website=] (WHO) }}</ref> 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, ], and ].<ref>{{cite web |url=https://www.drugs.com/sfx/naloxone-side-effects.html |title=Naloxone Side Effects in Detail |website=Drugs.com |access-date=5 May 2015 |url-status=live |archive-url=https://web.archive.org/web/20150507072325/http://www.drugs.com/sfx/naloxone-side-effects.html |archive-date=7 May 2015 }}</ref><ref name="pmid3662194">{{cite journal | vauthors = Schwartz JA, Koenigsberg MD | title = Naloxone-induced pulmonary edema | journal = Annals of Emergency Medicine | volume = 16 | issue = 11 | pages = 1294–1296 | date = November 1987 | pmid = 3662194 | doi = 10.1016/S0196-0644(87)80244-5 }}</ref>

Naloxone has been shown to block the action of pain-lowering ]s the body produces naturally. These endorphins likely operate on the same opioid receptors that naloxone blocks. It is capable of blocking a ] pain-lowering response if the placebo is administered together with a hidden or blind injection of naloxone.<ref name="pmid15820838">{{cite journal | vauthors = Sauro MD, Greenberg RP | title = Endogenous opiates and the placebo effect: a meta-analytic review | journal = Journal of Psychosomatic Research | volume = 58 | issue = 2 | pages = 115–120 | date = February 2005 | pmid = 15820838 | doi = 10.1016/j.jpsychores.2004.07.001 }}</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=14 September 2016|work=Science in the News|access-date=14 November 2017|archive-date=15 November 2017|archive-url=https://web.archive.org/web/20171115015402/http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/|url-status=live}}</ref><ref>{{cite journal | vauthors = Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I | title = Open-label placebo treatment in chronic low back pain: a randomized controlled trial | journal = Pain | volume = 157 | issue = 12 | pages = 2766–2772 | date = December 2016 | pmid = 27755279 | pmc = 5113234 | doi = 10.1097/j.pain.0000000000000700 }}</ref>

Naloxone should be used with caution in people with cardiovascular disease as well as those who are currently taking medications that could have adverse effects on the cardiovascular system such as causing ], ] (pulmonary edema), and ]. There have been reports of abrupt reversals with opioid antagonists leading to pulmonary edema and ].<ref name="uptodate_naloxone_contra">{{cite web|url=https://www.uptodate.com/contents/naloxone-drug-information|title=Naloxone: Contraindications|website=]|access-date=31 October 2017|url-access=subscription|archive-date=20 May 2016|archive-url=https://web.archive.org/web/20160520232432/http://www.uptodate.com/contents/naloxone-drug-information|url-status=live}}</ref>

Use of naloxone to treat people who have been using opioids recreationally may cause acute ] with distressing physiological symptoms such as shivering, ], and nausea; these in turn may lead to aggression and reluctance to receive further treatment.<ref name=ukpg>{{cite web |type=Practice guideline |page=181 |url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/673978/clinical_guidelines_2017.pdf |date=November 2017 |publisher=] |title=Drug misuse and dependence: UK guidelines on clinical management }}</ref>

==Pharmacology==

===Pharmacodynamics===
{| class="wikitable floatright" style="text-align: center;"
|+ Naloxone at opioid receptors
|-
! rowspan="2" | Compound || colspan="3" |] ({{abbrlink|K<sub>i</sub>|Inhibitor constant}}) || Ratios || rowspan="2" | Refs
|-
!{{abbrlink|MOR|μ-Opioid receptor}}!!{{abbrlink|DOR|δ-Opioid receptor}}!!{{abbrlink|KOR|κ-Opioid receptor}}!! MOR:DOR:KOR
|-
| Naloxone || 1.1 nM<br />1.4 nM || 16 nM<br />67.5 nM || 12 nM<br />2.5 nM || 1:15:11<br />1:48:1.8 ||<ref name="pmid2986989">{{cite journal | vauthors = Tam SW | title = (+)-SKF 10,047, (+)-ethylketocyclazocine, mu, kappa, delta and phencyclidine binding sites in guinea pig brain membranes | journal = European Journal of Pharmacology | volume = 109 | issue = 1 | pages = 33–41 | date = February 1985 | pmid = 2986989 | doi = 10.1016/0014-2999(85)90536-9 }}</ref><br /><ref name="pmid9686407">{{cite journal | vauthors = Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS | display-authors = 6 | title = Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications | journal = NIDA Research Monograph | volume = 178 | pages = 440–466 | date = March 1998 | pmid = 9686407 }}</ref><ref name="pmid31376930">{{cite journal | vauthors = Clark SD, Abi-Dargham A | title = The Role of Dynorphin and the Kappa Opioid Receptor in the Symptomatology of Schizophrenia: A Review of the Evidence | journal = Biological Psychiatry | volume = 86 | issue = 7 | pages = 502–511 | date = October 2019 | pmid = 31376930 | doi = 10.1016/j.biopsych.2019.05.012 | s2cid = 162168648 | doi-access = free | title-link = doi }}</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 = The Journal of Pharmacology and Experimental Therapeutics | volume = 274 | issue = 3 | pages = 1263–1270 | date = September 1995 | pmid = 7562497 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7562497 | access-date = 13 December 2014 | archive-date = 12 March 2020 | archive-url = https://web.archive.org/web/20200312134749/http://jpet.aspetjournals.org/content/274/3/1263.long | url-status = live }}</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 = Molecular Pharmacology | volume = 45 | issue = 2 | pages = 330–334 | date = February 1994 | pmid = 8114680 | url = http://molpharm.aspetjournals.org/content/45/2/330.short | access-date = 22 June 2018 | archive-date = 22 June 2018 | archive-url = https://web.archive.org/web/20180622111441/http://molpharm.aspetjournals.org/content/45/2/330.short | url-status = live }}</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 ] compound that acts as a ] and ] ].<ref name="NHM-Naloxone pharmacology">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE | veditors = 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 FDA label">{{cite web | title=Narcan- naloxone hydrochloride spray Narcan- naloxone hydrochloride spray | website=DailyMed | date=7 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=724df050-5332-4d0a-9a5f-17bf08a547e1 | access-date=12 May 2020 | archive-date=30 January 2016 | archive-url=https://web.archive.org/web/20160130063652/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=724df050-5332-4d0a-9a5f-17bf08a547e1 | url-status=live }}</ref> The ] 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|access-date=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|archive-date=16 November 2017|archive-url=https://web.archive.org/web/20171116132555/http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638|url-status=live}}</ref> Naloxone's ] is highest for the ] (MOR), then the ] (DOR), and lowest for the ] (KOR);<ref name="NHM-Naloxone pharmacology"/> naloxone has negligible affinity for the ].<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|access-date=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.|archive-date=21 October 2017|archive-url=https://web.archive.org/web/20171021111918/http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=50|url-status=live}}</ref>

If naloxone is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs, except the inability of the body to combat pain naturally.{{Citation needed|date=October 2021}} 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 opioid receptors within the brain (a competitive antagonist, not a direct agonist), thereby preventing the action of both ] and ] opioids on these receptors without directly producing any effects itself.<ref name="DailyMed">{{cite web|title=Naloxone Hydrochloride injection, solution|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8535cc84-ad4a-4d67-8480-fb5a2e3406f8|publisher=DailyMed |access-date=21 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140422232959/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8535cc84-ad4a-4d67-8480-fb5a2e3406f8|archive-date=22 April 2014}}</ref>

A single administration of naloxone at a relatively high dose of 2{{nbsp}}mg by ] has been found to produce brain MOR blockade of 80% at 5{{nbsp}}minutes, 47% at 2{{nbsp}}hours, 44% at 4{{nbsp}}hours, and 8% at 8{{nbsp}}hours.<ref name="ColasantiLingford-HughesNutt2013">{{cite book | veditors = Miller PM | title = Biological Research on Addiction | series = Comprehensive Addictive Behaviors and Disorders | volume = 2 | vauthors = Colasanti A, Lingford-Hughes A, Nutt D | chapter = Opioids Neuroimaging | date = 2013 | pages = 675–687 | publisher = Elsevier | doi = 10.1016/B978-0-12-398335-0.00066-2 | isbn = 9780123983350 }}</ref> A low dose (2{{nbsp}}μg/kg) produced brain MOR blockade of 42% at 5{{nbsp}}minutes, 36% at 2{{nbsp}}hours, 33% at 4{{nbsp}}hours, and 10% at 8{{nbsp}}hours.<ref name="ColasantiLingford-HughesNutt2013" /> ] of naloxone via ] has likewise been found to rapidly occupy brain MORs, with peak occupancy occurring at 20{{nbsp}}minutes, peak occupancies of 67% at a dose of 2{{nbsp}}mg and 85% with 4{{nbsp}}mg, and an estimated half-life of occupancy disappearance of approximately 100{{nbsp}}minutes (1.67{{nbsp}}hours).<ref name="van WaardeAbsalomVisser2020">{{cite book | veditors = Dierckx RA, Otte A, De Vries EF, Van Waarde A, Luiten PG | title = PET and SPECT of Neurobiological Systems | vauthors = Waarde AV, Absalom AR, Visser AK, Dierckx RA | chapter = Positron Emission Tomography (PET) Imaging of Opioid Receptors | date = 30 September 2020 | pages = 749–807 | publisher = Springer International Publishing | doi = 10.1007/978-3-030-53176-8_21 | isbn = 978-3-030-53175-1 | s2cid = 241535315 | url = https://research.rug.nl/en/publications/db18f24c-9750-46f6-932d-634dac427c45 | chapter-url = https://research.rug.nl/en/publications/db18f24c-9750-46f6-932d-634dac427c45 | access-date = 23 January 2023 | archive-date = 9 March 2023 | archive-url = https://web.archive.org/web/20230309063205/https://research.rug.nl/en/publications/positron-emission-tomography-pet-imaging-of-opioid-receptors-2 | url-status = live }}</ref><ref name="pmid30867551">{{cite journal | vauthors = Johansson J, Hirvonen J, Lovró Z, Ekblad L, Kaasinen V, Rajasilta O, Helin S, Tuisku J, Sirén S, Pennanen M, Agrawal A, Crystal R, Vainio PJ, Alho H, Scheinin M | display-authors = 6 | title = Intranasal naloxone rapidly occupies brain mu-opioid receptors in human subjects | journal = Neuropsychopharmacology | volume = 44 | issue = 9 | pages = 1667–1673 | date = August 2019 | pmid = 30867551 | pmc = 6785104 | doi = 10.1038/s41386-019-0368-x }}</ref>

===Pharmacokinetics===
When administered ] (non-orally or non-rectally, 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="DailyMed"/> For people with liver diseases such as ] or ], naloxone usage has not been shown to increase serum liver enzyme levels.<ref>{{Citation|title=Naloxone|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK548244/|work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31643568|access-date=30 October 2019|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828181317/https://www.ncbi.nlm.nih.gov/books/NBK548244/|url-status=live}}</ref>

Naloxone has low systemic bioavailability when ] 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 = 105–109 | date = January 2000 | pmid = 10601678 | doi = 10.1016/S0304-3959(99)00185-2 | s2cid = 42230143 }}</ref>


==Chemistry== ==Chemistry==
Naloxone, also known as N-allylnoroxymorphone or as 17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one, is a ] ] ] and was derived from ] (14-hydroxydihydromorphinone), an opioid analgesic.<ref name="DeanBilsky2009">{{cite book| vauthors = Dean R, Bilsky EJ, Negus SS |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| vauthors = Nagase H |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">{{cite web | url=http://webbook.nist.gov/cgi/cbook.cgi?ID=C465656 | title=Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, (5α)- | access-date=20 November 2017 | archive-date=1 December 2017 | archive-url=https://web.archive.org/web/20171201041953/http://webbook.nist.gov/cgi/cbook.cgi?ID=C465656 | url-status=live }}</ref> Oxymorphone, in turn, was derived from ], an opioid analgesic and ] constituent of the ].<ref name="SeppalaRose2011">{{cite book|vauthors=Seppala MD, Rose ME|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–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020758/https://books.google.com/books?id=HkXXDQAAQBAJ&pg=PT143|url-status=live}}</ref> Naloxone is a ] of two ]s, (–)-naloxone (levonaloxone) and ] (dextronaloxone), only the former of which is active at opioid receptors.<ref name="Bennett2006">{{cite book|vauthors=Bennett LA|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–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020758/https://books.google.com/books?id=aIDGy72xseMC&pg=PA9|url-status=live}}</ref><ref name="Wang2003">{{cite book|vauthors=Wang JQ|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–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020759/https://books.google.com/books?id=cuxYNGtzSTIC&pg=PA44|url-status=live}}</ref> The drug is highly ], 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 ], ], ], ], and ].<ref name="BruntonChabner2010">{{cite book|vauthors=Brunton L, Chabner B, Knollman B|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|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020759/https://books.google.com/books?id=bVUfAQAAQBAJ|url-status=live}}</ref>
Naloxone is ] from ]. The ] of naloxone resembles that of ], the only difference being the substitution of the ]-] ] with an ] (prop-2-enyl) group. The name ''naloxone'' has been derived from '''''N''-al'''lyl and '''ox'''ymorph'''one'''.


==Administration== ==History==
Naloxone was patented in 1961 by Mozes J. Lewenstein, ], and the company ].<ref name="nyti_Jack"/> It was approved for opioid use disorder treatment in the United States in 1971.<ref>{{cite web | title=Naloxone: FDA-Approved Drugs | publisher=U.S. ] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=016636 | access-date=13 May 2020 | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804041436/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=016636 | url-status=live }}</ref>
Naloxone is most commonly injected ] for fastest action. The drug generally acts within a minute, and its effects may last up to 45 minutes. It can also be administered via ] or subcutaneous injection. Use of a wedge device (nasal atomizer) attached to a syringe to create a mist delivering the drug to the nasal ]<ref name="titleJournal of Emergency Nursing">{{cite web |url=http://www.jenonline.org/article/PIIS0099176704000078/fulltext?browse_volume=30&issue_key=TOC%40%40JOURNALS%40YJENU%400030%400002&issue_preview=no&select1=no&select1=no&vol=#section7 |title=Journal of Emergency Nursing |accessdate= |format= |work=}}</ref> may also be utilized, although this solution is more likely utilized outside of a clinical facility.


==Society and culture==
==Uses==
{{Ref improve section|date=July 2008}}


===Misinformation===
=== Counteracting opiate overdose and addiction ===
Naloxone has been distributed as part of emergency kits to ] users, and this has been shown to reduce rates of fatal ]. Projects of this type are under way in ], ], ], ], ], ], ], ], and ], with pilot projects started in ] in 2006 {{Citation needed|date=January 2010}}. Also in the UK, in December 2008 the Welsh Assembly Government announced 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}}</ref> While naloxone is still often used in emergency treatments for opioid overdose, its clinical use in the long-term treatment of opioid ] is being increasingly superseded by ]. Naltrexone is structurally similar but has a slightly increased affinity for κ-opioid receptors over naloxone, can be administered orally, and has a longer duration of action.


Naloxone has been subject to much inaccurate media reporting and many ]s about it have become prevalent.<ref name=legends>{{cite journal |vauthors=Crabtree A, Masuda JR |title=Naloxone urban legends and the opioid crisis: what is the role of public health? |journal=BMC Public Health |volume=19 |issue=1 |pages=670 |date=May 2019 |pmid=31146721 |pmc=6543555 |doi=10.1186/s12889-019-7033-5 |url= |doi-access=free }}</ref>
] naloxone has been successfully used in the reduction of ] and ] associated with opioid therapy in mechanically-ventilated acute care patients.


One such myth is that naloxone makes the recipient violent.<ref name=debunked>{{cite web |publisher=Indiana State Department of Health |url=https://www.in.gov/health/overdose-prevention/files/47_naloxone-myths-debunked.pdf |type=pdf |title=Naloxone myths debunked |accessdate=7 September 2023}}</ref> Another is that events called "Lazarus parties" have taken place, in which people reportedly took fatal overdoses in anticipation of being treated with naloxone; in reality this was a fiction spread by the police.<ref name=legends/> Yet another is the claim that people have indulged in "yo-yoing", whereby they would take naloxone and opioids simultaneously to enjoy an extreme "high" and subsequent revival; the idea is scientifically nonsensical.<ref name=legends/>
The combination ] is used for the treatment of opioid-induced constipation under the trade name ''Targin'' and in the ] under ''Targinact''.<ref>{{cite journal|author=Simpson K, et al.|title=Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain|journal=Curr Med Res Opin|volume=24|issue=12|pages=3503–3512|date=2008 Dec|url=http://www.informapharmascience.com/doi/abs/10.1185/03007990802584454|doi=10.1185/03007990802584454|pmid=19032132|accessdate=2009-04-09}}</ref>


===Names===
=== Preventing opioid abuse ===
Naloxone is its ], ], ], ], and ], while naloxone hydrochloride is its ] and ].<ref name="Elks2014">{{cite book|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA851|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|vauthors=Elks J|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=851–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020759/https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA851|url-status=live}}</ref><ref name="IndexNominum2000">{{cite book|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA715|title=Index Nominum 2000: International Drug Directory|publisher=Taylor & Francis|year=2000|isbn=978-3-88763-075-1|pages=715–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020800/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA715|url-status=live}}</ref><ref name="MortonHall2012">{{cite book|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA189|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms| vauthors = Morton IK, Hall JM |date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=189–}}</ref><ref name="Drugs.com">{{cite web|url=https://www.drugs.com/international/naloxone.html|title=Naloxone|access-date=20 November 2017|archive-date=1 December 2017|archive-url=https://web.archive.org/web/20171201044530/https://www.drugs.com/international/naloxone.html|url-status=live}}</ref>
Naloxone is used as a secondary chemical in the drug ]. Suboxone and ] were created to help ]-addicted patients ]. Suboxone contains four parts ] and one part naloxone, while Subutex contains only buprenorphrine. Naloxone was added to Suboxone in an effort to dissuade patients from grinding it up for abuse in combination with opiates. Intravenously administered naloxone is supposed to block the effects of any opiates and cause the user to go into immediate withdrawal. Oral or ] administration affects only the ], and has the added benefit of helping to reverse ] and lowered bowel motility caused by chronic medical use, or abuse, of a variety of opioids. Because of possible side effects of naloxone in some patients, chemical detox is often begun with Suboxone's sister drug, ], which does not contain naloxone.


The ] has expired and it is available as a ]. Several formulations use patented dispensers (spray mechanisms or autoinjectors), and patent disputes over the generic forms of the nasal spray were litigated between 2016 and 2020 when a judge ruled in favor of Teva, the generic manufacturer.<ref>{{cite web|title=Teva Invalidates Opiant Patents In Narcan Suit - Law360|url=https://www.law360.com/articles/1280639/teva-invalidates-opiant-patents-in-narcan-suit|access-date=5 January 2022|website=www.law360.com|archive-date=7 January 2022|archive-url=https://web.archive.org/web/20220107035328/https://www.law360.com/articles/1280639/teva-invalidates-opiant-patents-in-narcan-suit|url-status=live}}</ref> Teva announced entry of the first generic nasal spray formulation in December 2021.<ref name="Teva Pharmaceuticals_2021">{{cite press release | title=Teva Announces Launch of First-to-Market Generic Version of Narcan (Naloxone Hydrochloride Nasal Spray), in the U.S. | publisher=Teva Pharmaceuticals | via=Business Wire | date=22 December 2021 | url=https://www.businesswire.com/news/home/20211222005564/en/ | access-date=2 August 2023}}</ref> Brand names of naloxone include Narcan, Kloxxado, Nalone, Evzio, Prenoxad Injection, Narcanti, Narcotan, and Zimhi, among others.
=== Depersonalization disorder ===
A recent Russian study has shown that naloxone can be used to successfully treat ]. According to the study: "In three of 14 patients, ] symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization."<ref name="pmid11448093">{{cite journal |author=Nuller YL, Morozova MG, Kushnir ON, Hamper N |title=Effect of naloxone therapy on depersonalization: a pilot study |journal=J. Psychopharmacol. (Oxford) |volume=15 |issue=2 |pages=93–5 |year=2001 |month=June |pmid=11448093 |doi= 10.1177/026988110101500205|url=http://jop.sagepub.com/cgi/pmidlookup?view=long&pmid=11448093}}</ref>


===Legal status and availability to law enforcement and emergency personnel===
== Side-effects ==
{{Globalize|date=September 2022|2=US|3=Canada|talk=Talk:Naloxone#North-America-centric_legal_status_section|section}}
Possible side effects include: change in mood, increased sweating, nausea, nervousness, restlessness, trembling, vomiting, allergic reactions such as rash or swelling, dizziness, fainting, fast or irregular pulse, flushing, headache, heart rhythm changes, seizures, sudden chest pain.<ref>http://www.drugs.com/sfx/naloxone-side-effects.html</ref>
Naloxone (Nyxoid) was approved for use in the European Union in September 2017.<ref name="Nyxoid EPAR">{{cite web | title=Nyxoid EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/nyxoid | access-date=12 May 2020 | archive-date=5 April 2020 | archive-url=https://web.archive.org/web/20200405084842/https://www.ema.europa.eu/en/medicines/human/EPAR/nyxoid | url-status=live }}</ref>


In the United States, some nasal naloxone are legally available without a prescription.<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|vauthors=Suttles C|work=Wyoming Tribune Eagle|access-date=19 September 2018|archive-date=3 February 2018|archive-url=https://web.archive.org/web/20180203160745/https://www.wyomingnews.com/news/local_news/wyoming-s-albertsons-safeway-pharmacies-to-offer-narcan-over-the/article_ca4b259c-08ae-11e8-9f50-17a75174a10d.html|url-status=live}}</ref><ref>{{Cite web |last=Kekatos |first=Mary |date=May 15, 2024 |title=Walgreens announces it will sell generic version of over-the-counter Narcan |url=https://abcnews.go.com/Health/walgreens-announces-sell-generic-version-counter-narcan/story?id=110258916 |access-date=2024-08-10 |website=ABC News }}</ref>
Naloxone has been shown to block the action of pain-lowering ]s which the body produces naturally. The likely reason for this is that these endorphins operate on the same opioid receptors that Naloxone blocks. Naloxone is capable of blocking a ] pain-lowering response, both in clinical and experimental pain, if the placebo is administered together with a hidden or blind injection of naloxone.<ref>{{citation|authors=Sauro, Marie D; Greenberg, Roger P.|title=Endogenous opiates and the placebo effect: A meta-analytic review|journal=Journal of Psychosomatic Research|volume=58|number=2|date=Feb 2005|pages=115–120|url=http://maccurtain.com/psych/Sadistic%20Ben%20Mark2/Sauro%20and%20greenburg%202004%20endogenous%20opiates%20and%20the%20placebo%20effect.pdf|pmid=15820838}}</ref> Other studies have found that placebo alone can activate the body's μ-opioid endorphin system, delivering pain relief via the same receptor mechanism as morphine.<ref>http://www.jyi.org/news/nb.php?id=429</ref>


As of 2019, officials in 29 states had issued standing orders to enable licensed pharmacists to provide naloxone to patients without the individual first visiting a prescriber.<ref name="Network for Public Health Law">{{cite web|title=Addressing Opioid Overdose through Statewide Standing Orders for Naloxone Distribution|url=https://www.networkforphl.org/news-insights/addressing-opioid-overdose-through-statewide-standing-orders-for-naloxone-distribution/|access-date=5 January 2022|website=Network for Public Health Law|archive-date=6 January 2022|archive-url=https://web.archive.org/web/20220106000240/https://www.networkforphl.org/news-insights/addressing-opioid-overdose-through-statewide-standing-orders-for-naloxone-distribution/|url-status=live}}</ref> Prescribers working with harm reduction or low threshold treatment programs have also issued standing orders to enable these organizations to distribute naloxone to their clients.<ref>{{cite journal | vauthors = Wheeler E, Jones TS, Gilbert MK, Davidson PJ | title = Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 64 | issue = 23 | pages = 631–635 | date = June 2015 | pmid = 26086633 | pmc = 4584734 }}</ref> A standing order, also referred to as a "non-patient specific prescription" is written by a physician, nurse or other prescriber to authorize medicine distribution outside the doctor-patient relationship.<ref>{{cite web |title=Guide: Treating Heroin and Opioid Use Disorder |url=https://www.pa.gov/guides/opioid-epidemic/ |access-date=1 October 2020 |publisher=PA.Gov |archive-date=1 October 2020 |archive-url=https://web.archive.org/web/20201001131912/https://www.pa.gov/guides/opioid-epidemic/ |url-status=live }}</ref> In the case of naloxone, these orders are meant to facilitate naloxone distribution to people using opioids, and their family members and friends.<ref name="Network for Public Health Law" /> Over 200 naloxone distribution programs utilize licensed prescribers to distribute the drug through such orders, or through the authority of pharmacists (as with California's legal provision, ]).<ref name="Beletsky 2009">{{cite report |title=Closing Death's Door: Action Steps to Facilitate Emergency Opioid Drug Overdose Reversal in the United States |year=2009 |url=https://medicine.wright.edu/sites/medicine.wright.edu/files/page/attachments/Naloxonewhitepaper09.pdf |publisher=] |archive-url=https://web.archive.org/web/20230127043207/https://medicine.wright.edu/sites/medicine.wright.edu/files/page/attachments/Naloxonewhitepaper09.pdf |archive-date=27 January 2023 |ssrn=1437163 |vauthors=Beletsky L, Burris SC, Kral AH|doi=10.2139/ssrn.1437163 }}</ref><ref>{{cite SSRN|title=Stopping an Invisible Epidemic: Legal Issues in the Provision of Naloxone to Prevent Opioid Overdose|year=2009 |ssrn=1434381|vauthors=Burris SC, Beletsky L, Castagna CA, Coyle C, Crowe C, McLaughlin JM}}</ref>
== Legal status ==
The ] for Naloxone has expired and the drug is currently available in various ] forms.


Laws and policies in many US jurisdictions have been changed to allow wider distribution of naloxone.<ref>{{cite journal|vauthors=Davis C|title=Legal interventions to reduce overdose mortality: Naloxone access and overdose good samaritan laws|url=https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf|url-status=live|journal=Network for Public Health Law|archive-url=https://web.archive.org/web/20140903114828/https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf|archive-date=3 September 2014}}</ref><ref>{{cite journal | vauthors = Davis C, Webb D, Burris S | title = Changing law from barrier to facilitator of opioid overdose prevention | journal = The Journal of Law, Medicine & Ethics | volume = 41 | issue = Suppl 1 | pages = 33–36 | date = March 2013 | pmid = 23590737 | doi = 10.1111/jlme.12035 | s2cid = 22127036 }}</ref> In addition to laws or regulations permitting distribution of medicine to at-risk individuals and families, some 36 states have passed laws that provide naloxone prescribers with immunity against both civil and criminal liabilities.<ref>{{cite web | vauthors = Cutcliff A, Stringberg A, Atkins C |title=As Naloxone Accessibility Increases, Pharmacist's Role Expands|url=https://www.pharmacytimes.com/contributor/marilyn-bulloch-pharmd-bcps/2016/10/as-naloxone-accessibility-increases-pharmacists-role-expands|access-date=31 October 2019|website=Pharmacy Times|archive-date=31 October 2019|archive-url=https://web.archive.org/web/20191031180459/https://www.pharmacytimes.com/contributor/marilyn-bulloch-pharmd-bcps/2016/10/as-naloxone-accessibility-increases-pharmacists-role-expands|url-status=dead}}</ref> While paramedics in the US 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 before paramedics. As of 12 July 2015, law enforcement departments in 28 US 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 |access-date=12 July 2015 |url-status=live |archive-url=https://web.archive.org/web/20150713032125/http://www.nchrc.org/law-enforcement/us-law-enforcement-who-carry-naloxone/ |archive-date=13 July 2015 }}</ref> Programs training fire personnel in opioid overdose response using naloxone have also shown promise in the US, and efforts to integrate opioid fatality prevention into emergency response have grown due to the ].<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 = 1863–1864 | date = November 2012 | pmid = 23150005 | pmc = 3551246 | doi = 10.1001/jama.2012.14205 }}</ref><ref>{{cite journal| vauthors = Lavoie D|date=April 2012|title=Naloxone: Drug-Overdose Antidote Is Put In Addicts' Hands|url=https://www.huffingtonpost.com/2012/04/26/naloxone-drug-overdose-antidote_n_1456531.html|url-status=live|journal=Huffington Post|archive-url=https://web.archive.org/web/20120518161613/http://www.huffingtonpost.com/2012/04/26/naloxone-drug-overdose-antidote_n_1456531.html|archive-date=18 May 2012}}</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 Reduction Journal | volume = 6 | issue = 1 | pages = 16 | date = July 2009 | pmid = 19602236 | pmc = 2716314 | doi = 10.1186/1477-7517-6-16 | doi-access = free }}</ref><ref>{{cite report |year=2013|title=2013 National drug control strategy|url=https://obamawhitehouse.archives.gov//sites/default/files/ondcp/policy-and-research/ndcs_2013.pdf|url-status=live|archive-url=https://web.archive.org/web/20170121100239/https://obamawhitehouse.archives.gov/sites/default/files/ondcp/policy-and-research/ndcs_2013.pdf|archive-date=21 January 2017|publisher=] }}</ref>
== Identification ==
The ] of naloxone is 465-65-6; the anhydrous ] ] has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water, hydrochloride dihydrate, has CAS 51481-60-8.


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 ] said: "Naloxone gives individuals a second chance to get help".<ref>{{cite news| vauthors = Durando J |date=27 May 2014|title=NYPD officers to carry heroin antidote|newspaper=USA Today|url=https://www.usatoday.com/story/news/nation-now/2014/05/27/new-york-police-department-naloxone/9630299/|url-status=live|access-date=30 May 2014|archive-url=https://web.archive.org/web/20140703123154/http://www.usatoday.com/story/news/nation-now/2014/05/27/new-york-police-department-naloxone/9630299/|archive-date=3 July 2014}}</ref> ] Providers (EMS) routinely administer naloxone, except where basic Emergency Medical Technicians are prohibited by policy or by state law.<ref>{{cite journal | vauthors = Faul M, Dailey MW, Sugerman DE, Sasser SM, Levy B, Paulozzi LJ | 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 | volume = 105 | issue = Suppl 3 | pages = e26–e32 | date = July 2015 | pmid = 25905856 | pmc = 4455515 | doi = 10.2105/AJPH.2014.302520 }}</ref> In efforts to encourage citizens to seek help for possible opioid overdoses, many states have adopted Good Samaritan laws that provide immunity against certain criminal liabilities for anybody who, in good faith, seeks emergency medical care for either themselves or someone around them who may be experiencing an opioid overdose.<ref>{{cite web|title=Drug Overdose Immunity and Good Samaritan Laws|url=http://www.ncsl.org/research/civil-and-criminal-justice/drug-overdose-immunity-good-samaritan-laws.aspx|access-date=31 October 2019|website=www.ncsl.org|archive-date=13 September 2019|archive-url=https://web.archive.org/web/20190913233059/http://www.ncsl.org/research/civil-and-criminal-justice/drug-overdose-immunity-good-samaritan-laws.aspx|url-status=live}}</ref>
==References==
{{reflist|2}}


States including Vermont and Virginia have developed programs that mandate the prescription of naloxone when a prescription has exceeded a certain level of morphine ] per day as preventative measures against overdose.<ref>{{cite journal | vauthors = Jones CM, Compton W, Vythilingam M, Giroir B | title = Naloxone Co-prescribing to Patients Receiving Prescription Opioids in the Medicare Part D Program, United States, 2016-2017 | journal = JAMA | volume = 322 | issue = 5 | pages = 462–464 | date = August 2019 | pmid = 31386124 | pmc = 6686765 | doi = 10.1001/jama.2019.7988 }}</ref> Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in ], and have been replicated in the US military.<ref name="Beletsky 2009" /><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 Medicine | volume = 12 | issue = Suppl 2 | pages = S77–S85 | date = June 2011 | pmid = 21668761 | doi = 10.1111/j.1526-4637.2011.01128.x | doi-access = free | title-link = doi }}</ref>
==External links==

*
In Canada, naloxone single-use syringe kits are distributed and available at various clinics and emergency rooms. ] is increasing the distribution points for naloxone kits at all emergency rooms, and various pharmacies and clinics province-wide. All ] and ] patrol cars carry an emergency single-use naloxone syringe kit. Some ] 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. As of February 2016, pharmacies across ] and some other Canadian jurisdictions are allowed to distribute single-use take-home naloxone kits or prescribe the drug to people using opioids.<ref name="cbc.ca" />
* , by the International Programme on Chemical Safety

Following Alberta Health Services, ] reviewed the prescription-only status of naloxone, resulting in plans to remove it in 2016, making naloxone more accessible.<ref>{{cite news |url=https://www.cbc.ca/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 |website=CBC News |access-date=5 February 2016 |url-status=live |archive-url=https://web.archive.org/web/20160205205030/https://www.cbc.ca/news/health/naloxone-s-prescription-only-status-to-get-health-canada-review-1.3166867 |archive-date=5 February 2016 }}</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 |access-date=5 February 2016 |url-status=dead |archive-url=https://web.archive.org/web/20160205142858/http://www.health.alberta.ca/health-info/AMH-Naloxone-Take-home.html |archive-date=5 February 2016 }}</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 press release | title=Health Canada Statement on Change in Federal Prescription Status of Naloxone | publisher=] | date=14 January 2016 | url=https://www.canada.ca/en/health-canada/news/2016/01/health-canada-statement-on-change-in-federal-prescription-status-of-naloxone.html | access-date=6 October 2024}}</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=] |date=22 March 2017 |access-date=12 June 2017 |url-status=live |archive-url=https://web.archive.org/web/20170908140357/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/pdl-ord/pdl-ldo-qa-naloxone-qr-eng.php |archive-date=8 September 2017 }}</ref>

===Community access===
].]]In a survey of US laypersons in December 2021, most people believed the scientifically supported idea that trained bystanders can reverse overdoses with naloxone.<ref>{{cite journal | vauthors = Agley J, Xiao Y, Eldridge L, Meyerson B, Golzarri-Arroyo L | title = Beliefs and misperceptions about naloxone and overdose among U.S. laypersons: a cross-sectional study | journal = BMC Public Health | volume = 22 | issue = 1 | pages = 924 | date = May 2022 | pmid = 35538566 | pmc = 9086153 | doi = 10.1186/s12889-022-13298-3 | doi-access = free }}</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 other countries.<ref name="Beletsky 2009" />

]s for people who use opioids is underway in many North American cities.<ref name="cdc.gov">{{cite journal | title = Community-based opioid overdose prevention programs providing naloxone - United States, 2010 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 61 | issue = 6 | pages = 101–105 | date = February 2012 | pmid = 22337174 | pmc = 4378715 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm | url-status = live | archive-url = https://web.archive.org/web/20120426204807/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm | archive-date = 26 April 2012 | author1 = Centers for Disease Control Prevention (CDC) }}</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 | vauthors = Donkin K |access-date=5 May 2015 |url-status=live |archive-url=https://web.archive.org/web/20141205045540/http://www.thestar.com/news/gta/2012/09/09/toronto_naloxone_program_reduces_drug_overdoses_among_addicts.html |archive-date=5 December 2014 }}</ref> CDC estimates that the US programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its use prevented 10,000 opioid overdose deaths by 2014.<ref name="cdc.gov" />

In Australia, some forms of naloxone are available "over the counter" in pharmacies free without a prescription under the Take Home Naloxone programme. <ref name="doi 10.5694/mja15.01181">{{cite journal | vauthors = Lenton SR, Dietze PM, Jauncey M | title = Australia reschedules naloxone for opioid overdose | journal = The Medical Journal of Australia | volume = 204 | issue = 4 | pages = 146–147 | date = March 2016 | pmid = 26937664 | doi = 10.5694/mja15.01181 | url = https://www.mja.com.au/journal/2016/204/4/australia-reschedules-naloxone-opioid-overdose | access-date = 19 July 2020 | s2cid = 9320372 | archive-date = 19 July 2020 | archive-url = https://web.archive.org/web/20200719232637/https://www.mja.com.au/journal/2016/204/4/australia-reschedules-naloxone-opioid-overdose | url-status = live }}</ref><ref>{{cite news| vauthors = Davey M |date=29 January 2016|title=Selling opioid overdose antidote Naloxone over counter 'will save lives'|newspaper=The Guardian|url=https://www.theguardian.com/society/2016/jan/29/selling-opioid-overdose-antidote-naloxone-over-counter-will-save-lives|url-status=live|archive-url= https://web.archive.org/web/20161203055245/https://www.theguardian.com/society/2016/jan/29/selling-opioid-overdose-antidote-naloxone-over-counter-will-save-lives|archive-date=3 December 2016}}</ref><ref>{{cite web|date=1 February 2016|title=Why the 'heroin antidote' naloxone is now available in pharmacies|url=http://www.abc.net.au/triplej/programs/hack/how-painkiller-use-becomes-a-heroin-addiction/7129964|url-status=live|archive-url=https://web.archive.org/web/20160204040604/http://www.abc.net.au/triplej/programs/hack/how-painkiller-use-becomes-a-heroin-addiction/7129964|archive-date=4 February 2016|access-date=1 February 2016|work=ABC}}</ref> It comes in single-use filled syringe form similar to law enforcement kits as well as nasal sprays. In 2024, those with a prescription can purchase five doses for around AU$32 or just over AU$6 per dose.<ref>{{cite web|vauthors=Coulter E|date=27 August 2019|title=This drug can temporarily reverse an opioid overdose. So why aren't people using it?|url=https://www.abc.net.au/news/2019-08-27/naloxone-can-stop-an-overdose-why-arent-people-using-it/11448540|access-date=28 August 2019|website=ABC News|archive-date=27 August 2019|archive-url=https://web.archive.org/web/20190827192233/https://www.abc.net.au/news/2019-08-27/naloxone-can-stop-an-overdose-why-arent-people-using-it/11448540|url-status=live}}</ref><ref>{{Cite web |last=Pharmaceutical Benefit Scheme |title=PBS.gov.au {{!}} Naloxone |url=https://m.pbs.gov.au/search.html?term=NALOXONE&analyse=false |access-date=2024-10-30 |website=m.pbs.gov.au}}</ref>

In Alberta, in addition to pharmacy distribution, take-home naloxone kits are available and distributed in most drug treatment or rehabilitation centers.<ref name="cbc.ca">{{cite web | title=Naloxone kits now available at drug stores as province battles fentanyl crisis | website=CBC News | date=17 February 2016 | url=https://www.cbc.ca/news/canada/calgary/naloxone-kits-fentanyl-overdose-province-1.3451860 | access-date=9 March 2023 | archive-url=https://web.archive.org/web/20160304141621/http://www.cbc.ca/news/canada/calgary/naloxone-kits-fentanyl-overdose-province-1.3451860 |archive-date=4 March 2016 | url-status = live }}</ref>

In the European Union, take home naloxone pilots were launched in the Channel Islands and in Berlin in the late 1990s.<ref>{{cite journal | vauthors = Dettmer K, Saunders B, Strang J | title = Take home naloxone and the prevention of deaths from opiate overdose: two pilot schemes | journal = BMJ | volume = 322 | issue = 7291 | pages = 895–896 | date = April 2001 | pmid = 11302902 | doi = 10.1136/bmj.322.7291.895 | pmc = 30585 }}</ref> In 2008, the Welsh Assembly government announced its intention to establish demonstration sites for take-home naloxone,<ref>{{cite web|title=IHRA 21st International Conference Liverpool, 26th April 2010 - Introducing 'take home' Naloxone in Wales|url=http://www.ihra.net/files/2010/08/26/Danny_Morris.pdf|url-status=live|archive-url=https://web.archive.org/web/20110720062721/http://www.ihra.net/files/2010/08/26/Danny_Morris.pdf|archive-date=20 July 2011|access-date=9 March 2011}}</ref> and in 2010, Scotland instituted a national naloxone program.<ref>{{cite journal|vauthors=McAuley A, Best D, Taylor A, Hunter C, Robertson R|date=1 August 2012|title=From evidence to policy: The Scottish national naloxone programme|url=https://doi.org/10.3109/09687637.2012.682232|journal=Drugs: Education, Prevention and Policy|volume=19|issue=4|pages=309–319|doi=10.3109/09687637.2012.682232|s2cid=73263293|issn=0968-7637|access-date=6 January 2022|archive-date=9 March 2023|archive-url=https://web.archive.org/web/20230309063059/https://www.tandfonline.com/doi/full/10.3109/09687637.2012.682232?cookieSet=1|url-status=live}}</ref> Inspired by North American and European efforts, non-governmental organizations running programs to train drug users as overdose responders and supply them with naloxone are now operational in Russia, Ukraine, Georgia, Kazakhstan, Tajikistan, Afghanistan, China, Vietnam, and Thailand.<ref>{{cite web|url=https://www.opensocietyfoundations.org/publications/stopping-overdose|title=Stopping Overdose|publisher=Open Society Foundations|access-date=6 January 2022|archive-date=7 January 2022|archive-url=https://web.archive.org/web/20220107035410/https://www.opensocietyfoundations.org/publications/stopping-overdose|url-status=live}}</ref>

In 2018, a maker of naloxone announced it would provide a free kit including two doses of the nasal spray, as well as educational materials, to each of the 16,568 public libraries and 2,700 YMCAs in the U.S.<ref>{{cite magazine |title=Every U.S. Public Library and YMCA Will Soon Get Narcan for Free |url=https://time.com/5432950/narcan-libraries-ymca/ |magazine=Time |access-date=2 April 2019 |archive-date=1 April 2019 |archive-url=https://web.archive.org/web/20190401224345/http://time.com/5432950/narcan-libraries-ymca/ |url-status=live }}</ref>

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite book | title=Naloxone, Flumazenil and Dantrolene as Antidotes | publisher=Cambridge University Press | year=1993 | url=http://www.inchem.org/documents/antidote/antidote/ant01.htm | volume=1 | id=EUR 14797 EN | isbn=0-521-45459-X | series=IPCS/CEC Evaluation of Antidotes Series | access-date=15 February 2004 | archive-date=15 December 2003 | archive-url=https://web.archive.org/web/20031215213521/http://inchem.org/documents/antidote/antidote/ant01.htm | url-status=live }}
{{refend}}

== External links ==
* {{cite web | title=Naloxone Nasal Spray | publisher=] | url=https://medlineplus.gov/druginfo/meds/a616003.html }}
* {{cite web | title= Opioid Overdose Reversal Medications (OORM) | website=U.S. ] (SAMHSA | date=26 March 2024 | url=https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/opioid-overdose-reversal-medications }}


{{Antidotes}} {{Antidotes}}
{{Opioid receptor modulators}}
{{Sigma receptor modulators}}
{{Emergency medicine}}
{{Portal bar | Medicine}}
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