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The administration of the opioid antagonist naloxone in the community is a measure to prevent death from opioid overdose. Approved nasal naloxone sprays deliver initial doses of 0.9 to 8 mg. The level of the initial community dose is controversial, as the scientific base is weak. In this review knowledge of the pharmacokinetics of nasal, both approved and improvised nasal sprays, and intramuscular naloxone will be utilized to evaluate dose-effect relationships in previous studies of opioid overdose outcomes. The aim was to present scientifically based considerations on the initial nasal naloxone doses currently available, which reasonably balances the effect and adverse outcomes, given that at least two doses are at hand. Also included in these considerations is the challenge by illicitly manufactured fentanyl and analogs. This paper is based on both peer-reviewed and grey literature identified by several searches, of such as naloxone pharmacokinetics/formulations/outcomes/emergency medical services, in PubMed and Embase. There is little scientific evidence that supports the use of initial systemic dosing that exceeds 0.8 mg in the community. Higher doses increase the risk of withdrawal symptoms feared in people who use opioids. Many obstacles may reduce the potential of community-administered naloxone.

Pharmacokinetic considerations for community-based dosing of nasal naloxone in opioid overdose in adults