Take-home naloxone treatment for opioid emergencies: a comparison of routes of administration and associated delivery systems

ABSTRACT

Introduction: Naloxone reversal of opioid-induced respiratory depression outside of medical facilities has become more prevalent because of the escalating opioid epidemic in the USA. Take-home naloxone for treatment of opioid emergencies is now being recommended by numerous federal, state, and professional organizations.

Areas covered: The scope of the opioid overdose epidemic is reviewed along with practical, clinical, regulatory, and usability considerations for take-home naloxone routes of administration currently available and associated delivery systems. Specific opioid-related factors are discussed in detail with emphasis placed on life-threatening respiratory depression and naloxone antagonism. A clinical overview, including pharmacokinetic and FDA approval information for each take-home naloxone product is discussed in detail as well as the impact of take-home naloxone in the community. Finally, given these products are to be used in a panic-stricken, life-threatening opioid emergency, an analysis of available usability data is provided with proposed directions for further study.

Expert opinion: Based on the available clinical evidence, auto-injectable naloxone should be the preferred administration route for take-home naloxone treatment until additional safety, efficacy, and comparative outcomes data are available for unconventional routes of administration that unequivocally provide equal or superior results.

KEYWORDS:

• Auto-injector
• intranasal kit
• naloxone
• nasal spray
• opioid emergency
• opioid overdose
• opioid-induced respiratory depression

Article highlights

• Opioid-related factors including the duration of action, formulation, lipophilicity, dose, route of administration, initiation, titration, rotation or polyopioid use should be considered when managing a patient’s risk of life-threatening opioid-induced respiratory depression.

• The bioavailability of intranasal naloxone is lower than naloxone administered intramuscularly, requiring a higher dose to reach comparable systemic levels.

• Improvised intranasal naloxone (IN) kits have demonstrated take-home naloxone to be potentially beneficial in reducing opioid-related mortality rates.

• The take-home naloxone auto-injector and pre-assembled nasal spray provided substantial and adequate evidence of safety, efficacy and product quality, respectively, to obtain FDA approval with a new naloxone indication.

• Intramuscular (IM) naloxone has been shown to be significantly faster at improving the respiratory rate and to require a decreased amount of rescue naloxone as compared to the improvised IN naloxone kits.

• Rates of adverse events are similar after intranasal and intramuscular administration of naloxone.

• In simulated use testing, laypersons demonstrated a significant amount of difficulty in their ability to successfully administer a naloxone dose with the improvised IN kits, particularly when untrained (0% success untrained, 50% success one week after completing 1:1 training)

• In contrast, almost all laypersons are able to demonstrate successful administration of naloxone when using an auto-injector (94% without training and 100% one week after completing 1:1 training).

This box summarizes key points contained in the article.

Declaration of interest

E Edwards and M Elzey are employees of kaleo, Inc. J Fudin declares the following: AstraZeneca (speakers bureau, advisory board), Clarity (consultant), DepoMed (advisory board), Endo (speakers bureau, consultant), kaleo, Inc (speakers bureau, advisory board), Kashiv Pharma (consultant), KemPharm (consultant), Millennium Health, LLC (speakers bureau), Remitigate, LLC (founder, owner), Scilex Pharmaceuticals (consultant). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the preparation of this manuscript, it was funded by kaleo, Inc. and carried out by Laurie Orloski, PharmD (Pharmite), Complete Healthcare Communications, LLC.

Additional information

Funding

This paper was not funded.