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

Key Findings

No clinical studies on Naloxone Hydrochloride Nasal Spray (device pre-filled with naloxone) were identified.
The literature search identified two studies comparing intramuscular naloxone with naloxone administered intranasally using an atomization device. The two unblinded randomized controlled trials reported that treatment with intramuscular naloxone resulted in a higher proportion of patients who achieved adequate response, and, at least, a nominally faster mean time to achieve adequate response compared with naloxone administered intranasally using a mucosal atomizer. Both studies found that the proportion of patients who required rescue naloxone after the initial dose was significantly lower with intramuscular naloxone than with naloxone administered intranasally using a mucosal atomizer. In both studies, the incidence of adverse events was similar for naloxone administered intranasally using a mucosal atomizer and intramuscular naloxone. Common adverse events were mild agitation and/or violence; nausea and/or vomiting; and headache.

The 2015 American Heart Association Guidelines Update recommends intramuscular or intranasal naloxone as first aid treatment of patients with known or suspected opioid overdose. It also recommends that persons at risk for opioid overdose or those living with or in frequent contact with such persons be given opioid overdose response education, either alone or in combination with naloxone distribution and training.

The literature search did not identify any studies which evaluated the cost-effectiveness of Naloxone Hydrochloride Nasal Spray, naloxone administered intranasally using a mucosal atomizer, or intramuscular naloxone.


Intranasal and intramuscular naloxone for opioid overdose in the pre-hospital setting: a review of comparative clinical and cost-effectiveness, and guidelines. Ottawa: CADTH; 2017 Mar. (CADTH rapid response report: summary with critical appraisal).