Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?

Abstract

Context: Take-home naloxone is increasingly provided to prevent heroin overdose deaths. Naloxone 0.4-2.0 mg is licensed for use by injection. Some clinicians supply improvised nasal naloxone kits (outside licensed approval). Is this acceptable?

Aims: (1) To consider provision of improvised nasal naloxone in clinical practice and (2) to search for evidence for pharmacokinetics and effectiveness (versus injection).

Methods: (1) To document existing nasal naloxone schemes and published evidence of pharmacokinetics (systematic search of the CINAHL, Cochrane, EMBASE and MEDLINE databases and 18 records included in narrative synthesis). (2) To analyse ongoing studies investigating nasal naloxone (WHO International Clinical Trials Registry Platform and US NIH RePORT databases).

Findings: (1) Multiple studies report overdose reversals following administration of improvised intranasal naloxone. (2) Overdose reversal after nasal naloxone is frequent but may not always occur. (3) Until late 2015, the only commercially available naloxone concentrations were 0.4 mg/ml and 2 mg/2 ml. Nasal medications are typically 0.05-0.25 ml of fluid per nostril. The only published study of pharmacokinetics and bioavailability finds that nasal naloxone has poor bioavailability. QUESTIONS FOR DEBATE: (1) Why are pharmacokinetics and bioavailability data for nasal naloxone not available before incorporation into standard clinical practice? (2) Does nasal naloxone have the potential to become a reliable clinical formulation? (3) What pre-clinical and clinical studies should precede utilization of novel naloxone formulations as standard emergency medications?

Conclusions: The addictions treatment field has rushed prematurely into the use of improvised nasal naloxone kits. Evidence of adequate bioavailability and acceptable pharmacokinetic curves are vital preliminary steps, especially when effective approved formulations exist.

Keywords: Death; emergency; heroin; naloxone; nasal; opioid; overdose; unlicensed.