Administration of naloxone to prevent opioid overdose (intranasal/intramuscular)

Summary of the evidence

  • Beneficial

Naloxone administration (intranasal/intramuscular) was assessed in a systematic review (Chou et al., 2017, 13 studies) and results showed that:

  • at the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone,
  • 1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation 

Intranasal administration of naloxone was found in a review with meta-analysis (Yousefifard et al., 2020) to be as effective as intramuscular/intravenous administration in the pre-hospital management of opioid overdose:

  • the success rate (defined as the recovery of patients’ consciousness and spontaneous respiration) of the intranasal and intramuscular/intravenous administration of naloxone was 82.54% (95% CI: 57.97 to 97.89%) and 80.39% (95% CI: 57.38 to 96.04%) respectively with no difference between the two routes (OR=1.01; 95% CI: 0.42 to 2.43; P=0.98)
  • the prevalence of major side-effects was non-significant for both intranasal (0.00%) and intramuscular/intravenous (0.05%) routes and there was no difference in the prevalence of major (OR=1.18; 95% CI: 0.38 to 3.69; P=0.777) and minor (OR=0.64; 95% CI: 0.17 to 2.34; P=0.497) side-effects between the two routes.

The odds of needing a rescue dose were 2.17 times higher for intranasal naloxone than intramuscular/intravenous naloxone (OR=2.17; 95% CI: 1.53 to 3.09; P<0.0001), however since it does not require intravenous access and its re-administration does not cause serious complications, this limitation does not seem major enough to prevent its use.

Naloxone distribution was found in an umbrella review of systematic reviews (Razaghizad et al., 2021, 6 SR containing 87 unique studies) effective in:

  • reducing opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective.