No Survival Benefit to Higher Intranasal Naloxone Dose

There was no difference in survival between recipients of 4-mg or 8-mg intranasal naloxone (Narcan) administered by law enforcement, according to data from New York state.

A review of 354 naloxone administration reports from New York State Police from March 2022 to August 2023 showed that 99% of people who received the 8-mg dose and 99.2% of those who received the 4-mg dose survived (relative risk [RR] 0.81, 95% CI 0.07-8.99, P=0.86), reported Sharon Stancliff, MD, of the AIDS Institute at the New York State Department of Health, and colleagues.

There were also no significant differences in number of doses received, prevalence of most post-naloxone signs and symptoms, combativeness, or hospital transport refusal, they noted in the Morbidity and Mortality Weekly Report.

“This study suggests that there are no benefits to law enforcement administration of higher-dose naloxone,” Stancliff and co-authors wrote. “Additional data are needed to guide public health agencies in considering whether the 8-mg intranasal naloxone product provides benefits compared with the usual 4-mg intranasal naloxone product among community organizations, including law enforcement.”

Notably, opioid withdrawal signs and symptoms, including vomiting, were significantly more prevalent among 8-mg naloxone recipients (37.6%) versus 4-mg recipients (19.4%; RR 2.51, P<0.001). Vomiting specifically was noted in 20.8% and 13.8% of 8-mg and 4-mg recipients, respectively, but this was not significantly different by formulation (RR 1.64, 95% CI 0.90-2.98).

“However, the high prevalence of vomiting as an isolated sign in both groups is concerning because of the risk of aspiration in sedated persons,” Stancliff and team wrote.

Furthermore, opioid withdrawal symptoms are “very uncomfortable and could potentially lead to things like rapid reuse of opioids, or people being less likely to use or carry naloxone in the future,” co-author Emily Payne, MSPH, also of the AIDS Institute at the New York State Department of Health, told MedPage Today.

Recipients of the 8-mg intranasal naloxone product received an average of 1.58 doses (95% CI 1.45-1.72), for a mean of 12.6 mg of naloxone, while recipients of the 4-mg product received an average of 1.67 doses (95% CI 1.59-1.75), for a mean of 6.7 mg of naloxone.

Anger or combativeness as perceived by the responding law enforcement officer was reported in 10.9% of 8-mg recipients and 7.9% of 4-mg recipients (P=0.37), and hospital transport refusal did not differ significantly by formulation (19% vs 26.6%, P=0.14).

In 2021, the FDA approved an 8-mg intranasal naloxone product. That approval relied in part on data from the original FDA approval of naloxone, which leveraged reports from an FDA advisory committee and the NIH, “which both suggested that higher-dose initial opioid reversal agents were needed to effectively respond to overdoses from synthetic opioids, including fentanyl,” Stancliff and colleagues noted.

From March 26, 2022 to Aug. 16, 2023, the New York State Department of Health in collaboration with the New York State Police field-tested an 8-mg intranasal naloxone product across three of its 11 troops to be administered in instances of suspected opioid overdose. The three troops using the 8-mg dose products were all located in eastern New York.

In total, 436 naloxone administration reports were submitted, and 354 met inclusion criteria, resulting in 101 reports of 8-mg dose forms, and 253 4-mg dose forms. Exclusion criteria included absence of opioid toxidrome (i.e., respiratory depression or decreased consciousness), more than one naloxone formulation (i.e., both 4-mg and 8-mg products) used by law enforcement responders, and likely death before naloxone administration.

Naloxone administration reports were reviewed by two physicians at regular team meetings.

The main limitation of the study was its size, said Payne.

“With a larger sample size, we might have been able to detect other differences,” she noted. “Vomiting, lethargy, and disorientation were all higher in the 8-mg group, but those differences were small, and they didn’t reach statistical significance, which could partially be based on the fact that our group size was small.”

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