High-dose opioid reversal spray no better than lower dose in field, US study finds

By Thomson Reuters Feb 8, 2024 | 12:47 PM

(Reuters) – A high-dose version of the opioid reversal spray naloxone, made by Hikma Pharmaceuticals, did not result in an increased survival rate compared with lower-dose versions of the drug when administered in emergency situations by New York law enforcement, according to a U.S. study.

The analysis also suggests that those given the higher 8 milligram strength spray were more than twice as likely to experience opioid withdrawal symptoms compared to other sprays such as Narcan that use a 4 mg dose.

Naloxone rapidly reverses or blocks the effects of opioids, restoring normal respiration, especially when given within minutes of the first signs of an overdose.

The Hikma version, sold under the brand name Kloxxado, was approved in 2021 after U.S. Food and Drug Administration advisers and National Institutes of Health reports suggested that a high-dose version was needed to respond to overdoses by more potent opioids such as fentanyl.

The U.S. opioid epidemic has caused more than a half million overdose deaths over more than two decades, with fentanyl and synthetic versions a major culprit in recent years, according to government data.

According to the field study, 99.0% of those who received 8 mg of intranasal naloxone survived, as did 99.2% of those who received 4 mg.

The study, conducted by New York employees and published on Thursday by the U.S. Centers for Disease Control and Prevention, analyzed 436 detailed reports from New York State Police troopers from March 26, 2022 through Aug. 16, 2023. The reports included body-worn camera footage.

This was the first real-world data comparing the two doses and aligns with an earlier systemic review of reports from emergency departments, the study authors said.

Among those who received 8 mg naloxone, 37.6% showed signs of opioid withdrawal including vomiting, compared with 19.4% for those who got the 4 mg dose, the data showed.

Opioid withdrawal symptoms associated with the use of naloxone include vomiting, disorientation, lethargy, shivering, diarrhea and increased heart rate.

“Those on the frontlines of this public health epidemic need all FDA-approved treatment options available to them, which is why Hikma provides 8 mg nasal Kloxxado and generic injectable naloxone options to help meet the urgent needs of patients and communities,” the company said in a statement.

The study authors said their findings were limited by the fact that police personnel were not medical providers and that there may have been inconsistencies in the classification of post-naloxone administration symptoms.

Emergent Biosolutions’ Narcan, the first nasal spray emergency treatment for opioid overdose, was approved by the FDA in 2015 as a prescription drug at a 4 mg dose.

Apart from Emergent, Israel-based Teva Pharmaceutical Industries, Padagis Israel Pharmaceuticals and Amphastar Pharmaceuticals also manufacture 4 mg versions of naloxone nasal spray.

(Reporting by Mariam Sunny in Bengaluru; editing by Caroline Humer and Bill Berkrot)