Standard Dose Naloxone Effective

"Studies in two states in the US have found that there is no association between the introduction of fentanyl into the drug supply and naloxone dosing required to reverse opioid overdoses. This conclusion emerged from data collected over four years at a SSP in Pittsburgh, PA, that distributed primarily 0.4 mg IM naloxone to people who use drugs (Bell et al., 2019; Bell & Dasgupta, 2024). Although the proportion of opioid overdose deaths attributed to fentanyl grew from 3.5% in 2013 to 68.7% in 2016, the average number of doses of naloxone administered by SSP participants to reverse overdoses did not change significantly, 1.62 doses in 2013 and 1.52 doses in 2016. An additional study of the naloxone doses used in opioid reversals reported to this Pittsburgh SSP, from August 2005 to January 2023, found that from 2010 to 2023, the average dose per reversal was below two administered doses (Bell & Dasgupta, 2024). In Kentucky, Rock et al. evaluated emergency services personnel-administered intranasal-equivalent naloxone doses and observed a clinically insignificant increase from 4.5 mg to 4.7 mg over four years to reverse overdoses during which fentanyl became ubiqui­ tous in the drug supply (Rock et al., 2024). In both studies, the rate of successful overdose reversal was 99%.

"Administration of additional doses of naloxone or increasing the dose or half-life of a single product do not reverse an opioid overdose more quickly (Hill et al., 2022; Klebacher et al., 2017). In a 2018 literature review of naloxone dosing, administration, and timing, Lynn and Gal­ ankin conclude, “the interactions between the opioid agonist and the mu-opioid receptor may be the greatest determinant of the speed of recovery from the respiratory effects of many opioids, which may not markedly accelerate with increasing doses of naloxone, but rather respond to a minimum effective dose” (Rzasa Lynn & Galinkin, 2018)."