Pharmacokinetic Properties of Intranasal and Injectable Formulations of Naloxone for Community use: a Systematic Review

The US FDA has approved two naloxone products for use by laypersons in community settings for emergency treatment of known or suspected opioid overdose: an intranasal spray with a concentrated naloxone dose of 2 or 4 mg in 0.1 ml and an auto-injector for intramuscular (im.) or subcutaneous (sc.) use with a naloxone dose of 0.4 or 2 mg. In the absence of head-to-head, comparative efficacy studies, which are not feasible for ethical and logistical reasons, pharmacokinetic data provide important information about effective doses and routes of administration of naloxone for opioid overdose reversal. In pharmacokinetic studies, both the approved intranasal spray and the im./sc. auto-injector demonstrated bioequivalence with a previously approved formulation, indicating that naloxone exposure was adequate to reverse an opioid overdose. Both the approved intranasal spray and the im./sc. auto-injector demonstrated sufficient plasma exposure within the first 15-20 min after administration. Usability studies with laypersons in simulated overdose conditions have found that more than 90% of participants were able to successfully administer naloxone using the approved intranasal spray or im./sc. auto-injector without prior training; however, these studies have identified critical errors with the proper assembly and use of unapproved intranasal kits, even when training had been provided. Approved intranasal naloxone is appropriate for most patients, with the exception of those with known nasal pathology (e.g., polyps and chronic intranasal drug use).