Administers of Naloxone – the rapidly acting antidote that reverses the effects of overdose with opioids – have important gaps in knowledge about the safety and effectiveness of the drug, which is widely administered off-label among patients, families, friends and emergency responders, says a study published in the Annals of Internal Medicine.
“Naloxone is effective, but we really need to know the best way to administer it,” said senior author Roger Chou, M.D., director of the Pacific Northwest Evidence-based Practice Center at OHSU. “This has both cost and clinical implications.”
In 2015, the FDA approved two prescription versions of naloxone – an auto-injector and a nasal spray formulation. Many first responders have been using the less-concentrated injectable formulations of naloxone to reverse the effects of opioid overdose. In those emergency situations, they administer it through the nose.
This off-label use has been effectively used by law enforcement treating unconscious overdose victims, but it is researchers say they are uncertain how much naloxone is absorbed and how reliably it is administered. Both factors could impact the effectiveness of off-label use of naloxone compared with the more recent FDA-approved versions.
“The majority of naloxone being administered nasally is probably the non-approved formulation,” said co-author Mohamud Daya, M.D., professor of emergency medicine in the OHSU School of Medicine. “The sad thing is, we don’t know much about the new formulations. They’ve not actually been well studied in the way that you’d want them to be in a large population of patients.”
One thing clinicians and first responders do know is that the new FDA-approved formulations are expensive – costing as much as $4,000 for the auto-injector.
Researchers reviewed 13 published studies to determine how the route of administration and dosing outside the hospital affects mortality, reversal of overdose symptoms and harm. The evidence appeared to show similar effectiveness between the intramuscular and intranasal delivery for heroin or prescription opioid overdose, but the intranasal naloxone studied was at a concentration different than the FDA-approved nasal formulation.
Researchers also noted that little is known about the efficacy and safety of off-label use of naloxone for treating overdoses related to newly emerging illicit uses of more powerful opioids such as fentanyl and fentanyl derivatives.
“The off label may be fine for most overdoses related to standard heroin or prescription opioids, but may not be strong enough for these other drugs,” Chou said.
It’s important for new research to examine the effect of these off-label uses, he said.
“These jury-rigged intranasal devices have not been tested the same way,” Chou said. “The fact that we have no evidence on the off-label uses for these devices is concerning, especially because many first responders feel compelled to use them because of the cost differences.”