Naloxone

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Naloxone, sold under the brand name Narcan among others, is an opioid antagonist, a medication used to reverse or reduce the effects of opioids.<ref name="AHFS2015" /> For example, it is used to restore breathing after an opioid overdose.<ref name="AHFS2015" /> Effects begin within two minutes when given intravenously, five minutes when injected into a muscle,<ref name="AHFS2015" /> and ten minutes as a nasal spray.<ref>Template:Cite journal</ref> Naloxone blocks the effects of opioids for 30 to 90 minutes.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Administration to opioid-dependent individuals may cause symptoms of opioid withdrawal, including restlessness, agitation, nausea, vomiting, a 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It appears to be safe in pregnancy, after having been given to a limited number of women.<ref name=TGA2014>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Naloxone is a non-selective and competitive opioid receptor antagonist.<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/>

Naloxone was patented in 1961 and approved for opioid overdose in the United States in 1971.<ref name="nyti_Jack">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite patent Template:Webarchive</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref>

Medical uses

Opioid overdose

File:NaloxoneKit.jpg

A naloxone kit as distributed in British Columbia, Canada

Naloxone is useful in treating both acute opioid overdose and 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">Template:Cite journal</ref>

It is included as a part of emergency overdose response kits distributed to heroin, fentanyl, and other opioid drug users, and to emergency responders. This has been shown to reduce rates of deaths due to overdose.<ref name="pmid16956873">Template:Cite journal</ref> A prescription for naloxone is recommended if a person is on a high dose of opioid (>100Template:Nbspmg of morphine equivalence/day), is prescribed any dose of opioid accompanied by a benzodiazepine, or is suspected or known to use opioids nonmedically.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}Template:Page neededTemplate:Verify source</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">Template:Cite journal</ref>

Distribution of naloxone to individuals likely to encounter people who overdose is one aspect of harm reduction strategies.<ref>Template:Cite book</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>Template:Cite journal</ref>

Clonidine overdose

Naloxone can also be used as an antidote in an overdose of clonidine, a medication that lowers blood pressure.<ref>Template:Cite journal</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">Template:Cite journal</ref> However, there is controversy regarding naloxone's efficacy in treating the symptoms of clonidine overdose, namely slow heart rate, low blood pressure, and confusion/somnolence.<ref name="Ahmad et al 2015 Review"/> Case reports that used doses of 0.1Template:Nbspmg/kg (maximum of 2Template:Nbspmg/dose) repeated every 1–2 minutes (10Template:Nbspmg 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">Template:Cite journal</ref> The mechanism for naloxone's proposed benefit in clonidine overdose is unclear. Still, it has been suggested that endogenous opioid receptors mediate the sympathetic nervous system 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 buprenorphine and pentazocine, so that when swallowed or taken sublingually, only the non-naloxone opioid has an effect.<ref name="AHFS2015"/><ref name="Orman2009">Template:Cite journal</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, SAMHSA'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">Template:Cite book</ref>

Other uses

A 2003 meta-analysis of existing research showed naloxone to improve blood flow in patients with shock, including septic, cardiogenic, hemorrhagic, or spinal shock, but could not determine if this reduced patient deaths.<ref>Template:Cite journal</ref>

Oral naloxone has been used for opioid-induced constipation (OIC). A 2018 meta-analysis cites 5 studies that tests it for this purpose. It found that medical treatment for OIC can be more efficacious than placebo, but did not look into the effect of individual treatments such as naloxone. As a result, no conclusion can be drawn from the study on naloxone's effectiveness for OIC.<ref>Template:Cite journal</ref>

Special populations

Pregnancy and breastfeeding

Whether naloxone is excreted in breast milk is unknown, however, it is not orally bioavailable and therefore is unlikely to affect a breastfeeding infant.<ref>Template:Cite news</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">Template:Cite journal</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>Template:Cite journal</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 American Academy of Pediatrics 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 septic shock, naloxone safety and effectiveness are not established.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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 intravenously, with an onset of 1–2 minutes and a duration of up to 45 minutes.<ref name="Lexicomp. 2013">Template:Cite book</ref>

Intramuscular or subcutaneous

Naloxone can also be administered via intramuscular or subcutaneous injection. The onset of naloxone provided through this route is 2 to 5 minutes with a duration of around 30–120min.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite press release</ref> According to the FDA's National Drug Code Directory, a generic version of the auto-injector began to be marketed at the end of 2019.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite press release</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It was developed in a partnership between LightLake Therapeutics and the National Institute on Drug Abuse.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The approval process was fast-tracked.<ref>Template:Cite news</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 8Template:Nbspmg dose of intranasal naloxone developed by Hikma Pharmaceuticals.<ref>Template:Cite press release</ref> Citing the frequent need for multiple 4Template:Nbspmg doses of Narcan to successfully reverse overdose, packs of Kloxxado Nasal Spray contain two pre-packaged nasal spray devices, each containing 8Template:Nbspmg of naloxone.<ref>Template:Cite journal</ref><ref name="Kloxxado FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</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 nasalTemplate:Nbspmucosa.<ref name="pmid15039670">Template:Cite journal</ref> This is useful near facilities where many overdoses occur that already stock injectors.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

File:NARCAN teardown.jpg

Internal components of a naloxone nasal spray.

Side effects

Administration of naloxone to somebody who has used opioids may cause rapid-onset opioid withdrawal.<ref name=britch>Template:Cite journal</ref>

Naloxone has little to no effect if opioids are not present.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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, seizures, and pulmonary edema.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid3662194">Template:Cite journal</ref>

Naloxone has been shown to block the action of pain-lowering endorphins 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">Template:Cite journal</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>Template:Cite news</ref><ref>Template:Cite journal</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 low blood pressure, fluid accumulation in the lungs (pulmonary edema), and abnormal heart rhythms. There have been reports of abrupt reversals with opioid antagonists leading to pulmonary edema and ventricular fibrillation.<ref name="uptodate_naloxone_contra">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Use of naloxone to treat people who have been using opioids recreationally may cause acute opioid withdrawal with distressing physiological symptoms such as shivering, tachycardia, and nausea; these in turn may lead to aggression and reluctance to receive further treatment.<ref name=ukpg>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Pharmacology

Pharmacodynamics

Naloxone at opioid receptors

Compound	Affinities (Template:Abbrlink)			Ratios	Refs
	Template:Abbrlink	Template:Abbrlink	Template:Abbrlink	MOR:DOR:KOR
Naloxone	1.1 nM 1.4 nM	16 nM 67.5 nM	12 nM 2.5 nM	1:15:11 1:48:1.8	<ref name="pmid2986989">Template:Cite journal</ref> <ref name="pmid9686407">Template:Cite journal</ref><ref name="pmid31376930">Template:Cite journal</ref>
(−)-Naloxone	0.559 nM 0.93 nM	36.5 nM 17 nM	4.91 nM 2.3 nM	1:65:9 1:18:2	<ref name="pmid7562497">Template:Cite journal</ref> <ref name="pmid8114680">Template:Cite journal</ref>
(+)-Naloxone	3,550 nM >1,000 nM	122,000 nM >1,000 nM	8,950 nM >1,000 nM	1:34:3 Template:Abbr	<ref name="pmid7562497"/> <ref name="pmid8114680"/>

Naloxone is a lipophilic compound that acts as a non-selective and competitive opioid receptor antagonist.<ref name="NHM-Naloxone pharmacology">Template:Cite book</ref><ref name="Narcan FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The pharmacologically active isomer of naloxone is (−)-naloxone.<ref name="pmid7562497"/><ref name="Naloxone IUPHAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Naloxone's binding affinity is highest for the μ-opioid receptor (MOR), then the δ-opioid receptor (DOR), and lowest for the κ-opioid receptor (KOR);<ref name="NHM-Naloxone pharmacology"/> naloxone has negligible affinity for the nociceptin receptor.<ref name="Opioid receptor family – IUPHAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</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;<ref name="Naloxone effects on natural analgesia">Template:Cite journal</ref> since pure mu-opioid antagonists like naloxone and naltrexone block the effects of endorphins.<ref name="Opioid antagonists effects on endorphins">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Naloxone Drug Facts">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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 endogenous and xenobiotic opioids on these receptors without directly producing any effects itself.<ref name="DailyMed">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

A single administration of naloxone at a relatively high dose of 2Template:Nbspmg by intravenous injection has been found to produce brain MOR blockade of 80% at 5Template:Nbspminutes, 47% at 2Template:Nbsphours, 44% at 4Template:Nbsphours, and 8% at 8Template:Nbsphours.<ref name="ColasantiLingford-HughesNutt2013">Template:Cite book</ref> A low dose (2Template:Nbspμg/kg) produced brain MOR blockade of 42% at 5Template:Nbspminutes, 36% at 2Template:Nbsphours, 33% at 4Template:Nbsphours, and 10% at 8Template:Nbsphours.<ref name="ColasantiLingford-HughesNutt2013" /> Intranasal administration of naloxone via nasal spray has likewise been found to rapidly occupy brain MORs, with peak occupancy occurring at 20Template:Nbspminutes, peak occupancies of 67% at a dose of 2Template:Nbspmg and 85% with 4Template:Nbspmg, and an estimated half-life of occupancy disappearance of approximately 100Template:Nbspminutes (1.67Template:Nbsphours).<ref name="van WaardeAbsalomVisser2020">Template:Cite book</ref><ref name="pmid30867551">Template:Cite journal</ref>

Pharmacokinetics

When administered parenterally (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 alcoholic liver disease or hepatitis, naloxone usage has not been shown to increase serum liver enzyme levels.<ref>Template:Citation</ref>

Naloxone has low systemic bioavailability when taken by mouth due to hepatic first-pass metabolism, but it does block opioid receptors that are located in the intestine.<ref name="pmid10601678">Template:Cite journal</ref>

Chemistry

Naloxone, also known as N-allylnoroxymorphone or as 17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one, is a synthetic morphinan derivative and was derived from oxymorphone (14-hydroxydihydromorphinone), an opioid analgesic.<ref name="DeanBilsky2009">Template:Cite book</ref><ref name="Nagase2011">Template:Cite book</ref><ref name="NIST">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Oxymorphone, in turn, was derived from morphine, an opioid analgesic and naturally occurring constituent of the opium poppy.<ref name="SeppalaRose2011">Template:Cite book</ref> Naloxone is a racemic mixture of two enantiomers, (–)-naloxone (levonaloxone) and (+)-naloxone (dextronaloxone), only the former of which is active at opioid receptors.<ref name="Bennett2006">Template:Cite book</ref><ref name="Wang2003">Template:Cite book</ref> The drug is 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">Template:Cite book</ref>

History

Naloxone was patented in 1961 by Mozes J. Lewenstein, Jack Fishman, and the company Sankyo.<ref name="nyti_Jack"/> It was approved for opioid use disorder treatment in the United States in 1971.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Society and culture

Misinformation

Naloxone has been subject to much inaccurate media reporting and many urban legends about it have become prevalent.<ref name=legends>Template:Cite journal</ref>

One such myth is that naloxone makes the recipient violent.<ref name=debunked>{{#invoke:citation/CS1|citation |CitationClass=web }}</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/>

Names

Naloxone is its international nonproprietary name, British Approved Name, Dénomination Commune Française, Denominazione Comune Italiana, and Japanese Accepted Name, while naloxone hydrochloride is its United States Adopted Name and British Approved Name (Modified).<ref name="Elks2014">Template:Cite book</ref><ref name="IndexNominum2000">Template:Cite book</ref><ref name="MortonHall2012">Template:Cite book</ref><ref name="Drugs.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The patent has expired and it is available as a generic medication. 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Teva announced entry of the first generic nasal spray formulation in December 2021.<ref name="Teva Pharmaceuticals_2021">Template:Cite press release</ref> Brand names of naloxone include Narcan, Kloxxado, Nalone, Evzio, Prenoxad Injection, Narcanti, Narcotan, and Zimhi, among others.

Legal status and availability to law enforcement and emergency personnel

{{ safesubst:#invoke:Unsubst||date=__DATE__ |$B= Template:Ambox }} Naloxone (Nyxoid) was approved for use in the European Union in September 2017.<ref name="Nyxoid EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In the United States, some nasal naloxone are legally available without a prescription.<ref>Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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, AB1535).<ref name="Beletsky 2009">Template:Cite report</ref><ref>Template:Cite SSRN</ref>

Laws and policies in many US jurisdictions have been changed to allow wider distribution of naloxone.<ref>Template:Cite journal</ref><ref>Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</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 US overdose crisis.<ref name="Beletsky_2012">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="pmid19602236">Template:Cite journal</ref><ref>Template:Cite report</ref>

Following the use of the nasal spray device by police officers on Staten Island in New York, an additional 20,000 police officers began carrying naloxone in mid-2014. The state's Office of the Attorney General provided 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>Template:Cite news</ref> Emergency Medical Service Providers (EMS) routinely administer naloxone, except where basic Emergency Medical Technicians are prohibited by policy or by state law.<ref>Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

States including Vermont and Virginia have developed programs that mandate the prescription of naloxone when a prescription has exceeded a certain level of morphine milliequivalents per day as preventative measures against overdose.<ref>Template:Cite journal</ref> 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" /><ref name="pmid21668761">Template:Cite journal</ref>

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. 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. As of February 2016, pharmacies across Alberta 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" />

Following Alberta Health Services, Health Canada reviewed the prescription-only status of naloxone, resulting in plans to remove it in 2016, making naloxone more accessible.<ref>Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>Template:Cite press release</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Community access

File:Mendocino Pride 2023 - Sarah Stierch - 12.jpg

Free Narcan and test strips at a community event in Hopland, California.

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>Template:Cite journal</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 1Template:Nbspml ampoule of naloxone in the US is estimated to be significantly higher than in most other countries.<ref name="Beletsky 2009" />

Take-home naloxone programs for people who use opioids are underway in many North American cities.<ref name="cdc.gov">Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref><ref>Template:Cite news</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In the European Union, take home naloxone pilots were launched in the Channel Islands and in Berlin in the late 1990s.<ref>Template:Cite journal</ref> In 2008, the Welsh Assembly government announced its intention to establish demonstration sites for take-home naloxone,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and in 2010, Scotland instituted a national naloxone program.<ref>Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In 2018, a makerTemplate:Which 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>Template:Cite magazine</ref>

In 2025, an American start-up released a keychain case to make naloxone more immediately accessible in emergencies.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In April 2025, the city of Nashville, Tennessee introduced its first naloxone vending machine at a Twice Daily gas station on West End Avenue. This initiative, a collaboration between the Metro Nashville Health Department, Fund Recovery, and Twice Daily, aims to provide free access to naloxone, an opioid overdose-reversing medication. Within five weeks of installation, the machine dispensed over 2,200 doses, significantly surpassing initial expectations. Encouraged by this success, the health department plans to install three additional machines across Davidson County within 90 days, targeting areas with the highest overdose rates. The program is funded by opioid settlement money and underscores the importance of community partnerships in expanding access to life-saving interventions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Further reading

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