Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose

Kerr, Debra; Kelly, Anne‐Maree; Dietze, Paul; Jolley, Damien; Barger, Bill

doi:10.1111/j.1360-0443.2009.02724.x

Cited by 143 publications

(130 citation statements)

References 37 publications

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“…In first in-human trials, nasal naloxone was found to elicit withdrawal symptoms in opioid-dependent volunteers (Loimer et al, 1992(Loimer et al, , 1994. Since the early 2000s, nasal naloxone has been used off-label by ambulance personnel (Barton et al, 2005(Barton et al, , 2002Belz et al, 2006;Kelly et al, 2005;Kerr et al, 2009;Merlin et al, 2010;Robertson et al, 2009;Weber et al, 2012) and in the emergency department (Sabzghabaee et al, 2014). More recently, improvised nasal kits (consisting of a prefilled naloxone syringe and an atomizer which fits onto the syringe to generate a nasal spray) have been provided to opioid users, peers, and families in take-home naloxone trials (Doe-Simkins et al, 2009;Dwyer et al, 2015;Walley et al, 2013aWalley et al, , 2013b, and succesful overdose reversals using improvised nasal kits have also been reported for police first responders (Rando et al, 2015).…”

Section: Sublingualmentioning

confidence: 99%

“…In two ambulance-based clinical trials, intranasal naloxone had a substantial non-response rate: among opioid overdose victims, 26% (using 2mg/5mL nasal formulation; Kelly et al, 2005) and 18% (using 2mg/mL nasal formulation; Kerr et al, 2009) required a second rescue dose of naloxone (the second dose given IM).…”

Section: Intranasal Clinical Reports Describe Use Of Improvised Nasamentioning

confidence: 99%

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Naloxone without the needle − systematic review of candidate routes for non-injectable naloxone for opioid overdose reversal

Strang

McDonald

Alqurshi

et al. 2016

Drug and Alcohol Dependence

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. (2016). Naloxone without the needle systematic review of candidate routes for non-injectable naloxone for opioid overdose reversal. Drug and Alcohol Dependence. DOI: 10.1016DOI: 10. /j.drugalcdep.2016 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. After 40 years of injection-based naloxone treatment, non-injectable routes are finally being developed. Nasal naloxone has recently been approved and will soon be fieldtested, buccal naloxone holds promise, and it is unclear what sublingual naloxone will contribute. Development and approval of reliable non-injectable formulations will facilitate wider naloxone provision across the community internationally.

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Section: Sublingualmentioning

confidence: 99%

Section: Intranasal Clinical Reports Describe Use Of Improvised Nasamentioning

confidence: 99%

Naloxone without the needle − systematic review of candidate routes for non-injectable naloxone for opioid overdose reversal

Strang

McDonald

Alqurshi

et al. 2016

Drug and Alcohol Dependence

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“…Intranasal naloxone was explored in ambulance-based trials (Kelly et al, 2005;Kerr et al, 2009), but THN was halted by medico-legal concerns.…”

Section: Australiamentioning

confidence: 99%

Twenty years of take-home naloxone for the prevention of overdose deaths from heroin and other opioids—Conception and maturation

McDonald

Campbell

Strang

2017

Drug and Alcohol Dependence

113

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Highlights Deaths from opioid overdose can be prevented by prompt administration of naloxone  It has been 20 years since take-home naloxone provision was first proposed  Take-home naloxone programs have recently overcome legal barriers in many countries  Take-home naloxone provision remains low compared to evident growing clinical need  The 'opt-out' model of required pre-provision may achieve wider naloxone coverage Abstract Background: Opioid overdose is a major cause of mortality, but injury and fatal outcomes can be prevented by timely administration of the opioid antagonist naloxone. Pre-provision of naloxone to opioid users and family members (take-home naloxone, THN) was first proposed in 1996, and WHO Guidelines were issued in 2014. While widespread in some countries, THN is minimally available or absent elsewhere. This review traces the development of THN over twenty years, from speculative harm reduction proposal to public health strategy.Method: Medline and PsycINFO were searched for peer-reviewed literature using Boolean queries: 1) "naloxone OR Narcan"; 2) "(opioid OR opiate) AND overdose AND prevention". Grey literature and specialist websites were also searched. Data were extracted and synthesized as narrative review, with key events presented as chronological timeline. Results Conclusions:Framed as a public health tool for harm reduction, THN has overcome social, clinical, and legal barriers in many jurisdictions. Nonetheless, the rising death toll of opioid overdose illustrates that current THN coverage is insufficient, and greater public investment in overdose prevention will be required if THN is to achieve its full potential impact.

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“…naloxone was adjusted to be less than 1 ml per nostril [10]. Even though the pre-clinical studies may not have determined accurately the bioavailability of i.n.…”

Section: Commentariesmentioning

confidence: 99%

“…and i.m. administration (see Table 1); however, both studies found that adequate respiration occurred within 10 minutes of administration [9,10]. Table 1 Results of randomized studies comparing intranasal (i.n.)…”

mentioning

confidence: 99%

Tangled‐up and blue: releasing the regulatory chokehold on take‐home naloxone

Winstanley

2016

Addiction

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Naloxone is the most proximal intervention that we have to reduce premature mortality associated with unintentional opioid overdoses and it has been demonstrated to be highly efficacious, safe and cost-effective. The effectiveness of naloxone formulations may vary depending on the setting and the person responding to the overdose.Naloxone is the most proximal intervention that we have to reduce premature mortality associated with unintentional opioid overdoses. Opioid dependence causes a significant amount of disease burden globally [1], and an Australian study estimated that 86% of deaths among patients receiving opioid substitution therapy were potentially preventable [2]. It is important to contextualize the discussion of unlicensed drug formulations so that we can weigh the risks versus the benefits in response to this timely question raised by Strang and colleagues, as well as keep in mind that it is the formulation and not the drug itself that is the focus of debate.We have a health state that causes significant premature mortality globally and a reversal agent that is not only efficacious, but also has an excellent safety profile [3] and is highly cost-effective [4]. Intranasal (i.n.) naloxone is advantageous because it reduces the risk of needle-stick injuries and allows naloxone administration by emergency medical services (EMS) that are not certified for intramuscular (i.m.) or intravenous (i.v.) medication administration. While it would be ideal if regulations could be modified to allow all EMS to administer parenteral (i.m./i.v.) naloxone, this has proved to be a difficult front on which to make progress. To this point, a recent study in the United States found that only 38% of states allow basic level EMS to administer i.m. naloxone and there are no states that allow basic-level EMS to administer i.v. naloxone [5]. Another advantage of i.n. naloxone is that time to administration may be accomplished more quickly than i.v. administration among injection drug users (IDUs), whose chronic drug use can result in inaccessible, scarred veins [6]. Parenteral naloxone is believed to be superior to i.n. naloxone [7] however, there are important differences in outcomes based on whether the research was conducted in the pre-clinical or pre-hospital setting.A pre-clinical animal study found that i.n. naloxone, when maintained in the nasopharynx, was equivalent to i.v. naloxone in terms of bioavailability and duration of action [8]. A study in healthy volunteers found that i.n. naloxone had a faster onset (time to peak concentration) compared to i.m., but i.n. had poor bioavailability and a shorter duration of action [7]. This study found that i.m. naloxone had 36% bioavailability, reached peak concentration in 12 minutes and maintained measureable concentrations for nearly 4 hours; i.n. naloxone had 4% bioavailability, peak concentration within 6-9 minutes and measurable concentrations for nearly 3 hours [7]. Dowling and colleagues (2008) noted that this study was conducted with conscious healthy volunteers and...

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Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose

Abstract: Concentrated intranasal naloxone reversed heroin overdose successfully in 82% of patients. Time to adequate response was the same for both routes, suggesting that the i.n. route of administration is of similar effectiveness to the i.m. route as a first-line treatment for heroin overdose.

Cited by 143 publications

References 37 publications

Naloxone without the needle − systematic review of candidate routes for non-injectable naloxone for opioid overdose reversal

Naloxone without the needle − systematic review of candidate routes for non-injectable naloxone for opioid overdose reversal

Twenty years of take-home naloxone for the prevention of overdose deaths from heroin and other opioids—Conception and maturation

Tangled‐up and blue: releasing the regulatory chokehold on take‐home naloxone

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