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

Abstract

. (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.

International patent applications for non‐injectable naloxone for opioid overdose reversal: Exploratory search and retrieve analysis of the PatentScope database

“…To supplement and cross‐check the data obtained in Stages 1 and 2, we also searched PubMed for human PK data for non‐injectable naloxone using the Boolean search query ‘(nasal OR intranasal OR nose OR buccal OR sublingual) AND naloxone AND pharmacokinetics’ (see Table S1 for search protocol). These three routes of administration were chosen based on the systematic review .…”

“…A recent systematic review applied the FDA criteria to the peer‐reviewed literature and identified three candidate routes of administration for injection‐free naloxone delivery: IN, sublingual and buccal. However, at the time of the FDA approval of the first nasal spray, no results from clinical trials on the new nasal spray were published, and human PK data were only reported in one peer‐reviewed publication for an improvised IN naloxone spray formulation (2 mg 5 mL −1 ), with extremely low bioavailability (F = 4%) .…”

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

“…A systematic review identified nasal, buccal and sublingual naloxone delivery as the three viable routes for naloxone administration in an overdose emergency, of which study of the nasal route was most advanced (Strang et al, 2016a).…”

Letters toAddictionfrom Coffinet al.and Doe-Simpkinset al.re: ‘For Debate’ on clinical use of improvised nasal naloxone sprays: authors’ response

“…point to a potential nose‐to‐brain direct absorption and suggest that ‘blood bioavailability and pharmacokinetics may be the wrong yardstick by which to model nasal drug effects’. We have considered this briefly elsewhere where we have noted that Ehrick et al . do not consider it as a significant route of nasal absorption in man , and that Djupesland et al .…”

“…We have indeed sought to encourage the pharmaceutical industry to become involved in developing and delivering new forms of naloxone which would be better suited to this new application (mainly with very little success)—this includes better forms of injectable naloxone [e.g. pre‐filled syringes of naloxone (preferably with stake needle), more portable formulations of naloxone, better demonstrated and authorized shelf‐life], possible new non‐injectable naloxone formulations, such as concentrated nasal naloxone spray , and also potentially buccal naloxone (see for a recent review). We believe this collaboration is important, and we wish we had been able to be more influential and to stimulate earlier better developments.…”