Intranasal and Intramuscular Naloxone for Opioid Overdose in the Pre-Hospital Setting: A Review of Comparative Clinical and Cost-Effectiveness, and Guidelines

Key Message

One economic evaluation using a decision-analytic model with inputs from the medical literature and sources specific to Toronto showed that a school-based naloxone program to reduce opioid overdose mortality is likely to be cost-effective if there are at least two overdoses every year. A major limitation of the cost-effectiveness analysis was that, in the absence of data on incidence of overdoses on Canadian schools, the authors assumed between one overdose and 50 overdoses every 10 years across the entire 112 schools in the Toronto District School Board system¬, the subject of the study, without providing an adequate rationale for the assumption.

Based on evidence of very low quality, one guideline makes a weak recommendation that favors intranasal naloxone over intramuscular naloxone for patients with confirmed or suspected opioid overdose in out-of-hospital settings. Considerations for the recommendation were comparable efficacy across the two routes of administration, as well as ease of use and reduced adverse events associated with the intranasal formulation, which promotes increased safety of emergency medical service practitioners and patients. The guideline suggests that the initial dose should be enough to achieve adequate respiratory function without triggering withdrawal symptoms, considering factors such as the opioids in use in the local area. 

The literature search did not identify any evidence regarding the comparative effectiveness of Naloxone Hydrochloride Nasal Spray versus intramuscular naloxone or the intranasal administration of naloxone solution using a mucosal atomizer device. Also, no new evidence was identified comparing the clinical effectiveness of intranasal naloxone delivered by mucosal atomizer versus intramuscular naloxone other than that reported in a previously published CADTH Rapid Response report.