NEW YORK (Reuters Health) – Although higher-concentration intranasal naloxone seems to be as effective as intramuscular naloxone for out-of-hospital reversal of opioid overdose, there is limited evidence to determine how best to use naloxone in this setting.
“I think the most important message is that naloxone is effective for reversing opioid overdoses,” Dr. Roger Chou from Oregon Health and Science University, in Portland, told Reuters Health by email. “It is much better for patients to get FDA-approved naloxone formulations or off-label intranasal naloxone than no naloxone at all. We did not find any data to indicate that off-label intranasal naloxone should not be given – but it is important that, if it is used, patients be monitored carefully and be prepared to perform repeat dosing if needed.”
Naloxone is commonly used by emergency responders and laypersons in out-of-hospital settings to treat opioid overdose, but uncertainty remains about its optimal dosing and route of administration, as well as the best management after successful reversal of opioid overdose.
Dr. Chou and colleagues synthesized the pertinent evidence in their systematic review of 13 studies, published online November 28 in Annals of Internal Medicine.
In one trial, efficacy of a higher-concentration intranasal formulation (2 mg/mL) was similar to that of 2-mg intramuscular naloxone. In another trial, however, a lower-concentration intranasal formulation (2 mg per 5 mL) was less effective than intramuscular naloxone, according to measures of overdose symptoms.
There was insufficient evidence to evaluate other comparisons of naloxone’s route of administration, different doses via a given route of administration, alternative dose titration strategies, or variations in timing of repeated dosing.
Evidence to determine the effects of hospital transport versus non-transport after successful treatment of opioid overdose also was insufficient.
“I think the most surprising result was the lack of comparative studies on FDA-approved formulations of naloxone (the highly concentrated nasal spray and the auto-injector),” Dr. Chou said. “This makes it very difficult to know how the FDA-approved formulations perform compared to off-label, lower-concentration naloxone intranasally, which is commonly used because it is much less expensive than the FDA-approved formulations.”
“This is important because only a small volume can actually be absorbed intranasally (the rest just drips down the throat and is not bioavailable), so that people might be getting a lower effective dose of naloxone than administered,” he said. “Although lower doses may still be effective for many or most opioid overdoses, there are concerns that it may not be enough for overdoses due to highly potent fentanyl and fentanyl-like opioids, which are becoming more common and widespread.”
“Also, the auto-injector and the FDA-approved nasal formulation are designed to deliver a consistent dose even by untrained laypersons – the consistency of off-label intranasal dosing is not certain,” he said. “We also don’t know the optimal dose to administer (both the FDA-approved nasal formulation and the auto-injector come in different doses).”
“Other unanswered questions are whether patients need to be dosed until they are fully conscious or until they are spontaneously breathing but not necessarily fully conscious, with a potential trade-off of causing more withdrawal symptoms,” Dr. Chou said. “We found limited evidence that patients who refuse transport to a hospital after successful administration of naloxone seem to have a low risk of a serious adverse outcome, but we need more data to understand which patients require transport and whether there are other benefits of transport, such as linking patients to treatment for opioid-use disorder and preventing future overdose events.”
“Naloxone should be administered in a timely manner to maximize benefits and prevent opioid overdose death,” write Dr. Elizabeth M. Oliva from the Office of Mental Health and Suicide Prevention, VA Center for Innovation to Implementation, Menlo Park, California, and Dr. Mark Bounthavong from VHA Pharmacy Benefits Management Services, Academic Detailing Service, in Seattle, in an accompanying editorial. “Given increased distribution of naloxone to other first responders and layperson bystanders who may be present before EMS personnel, future investigations should examine whether naloxone delivery by these groups may have outcomes that are similar to, if not better than, waiting for EMS to arrive ‘in the nick of time.’”
SOURCES: http://bit.ly/2iVYQpp and http://bit.ly/2Ae9guE
Ann Intern Med 2017.
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