Improvised Nasal Naloxone Devices Might Deliver Insufficient Medication

By Will Boggs MD

April 01, 2019

NEW YORK (Reuters Health) - Improvised nasal naloxone devices (INND) commonly used by first responders and the general public deliver significantly less naloxone than regulator-approved devices, according to a study from the National Institute on Drug Abuse (NIDA).

"We definitely know that between the two nasal delivery systems, the improvised device is not as efficient at delivering naloxone to the bloodstream compared to the FDA-approved nasal Narcan spray," Dr. Philip A. Krieter from NIDA, in Bethesda, Maryland, told Reuters Health by email.

"Using the improvised device twice, 2 minutes apart, does not come close to reaching the naloxone blood level that is seen after one spray of nasal Narcan. It is important to note that the improvised device is not approved by the FDA," he said.

The improvised device, consisting of a prefilled naloxone syringe attached to a mucosal atomization device, has been used since 1994 by patients and first responders. In recent years, the U.S. Food and Drug Administration (FDA) has approved Narcan devices for nasal administration of naloxone as well as an autoinjector for intramuscular injection of naloxone, all of which can be used by nonmedical personnel for administering naloxone.

Dr. Krieter's team compared the pharmacokinetics of the FDA-approved devices and the INND in their study of 30 healthy volunteers of both sexes, 27 of which completed the study.

The peak plasma concentration (Cmax) was highest after intranasal administration of 4 mg of naloxone using the 4-mg FDA-approved Narcan spray device, similar when 2 mg of naloxone were administered using the autoinjector or the 2-mg FDA-approved Narcan spray device, and lowest when 2 and 4 mg were given by one or two intranasal doses using the INND.

The median time to reach Cmax (Tmax) was 20 minutes for all of the intranasal doses and slightly longer after the intramuscular dose, the researchers report in The Journal of Clinical Pharmacology, online March 12.

The total absorption (area under the concentration-time curve (AUC)) was approximately the same when 2 mg of naloxone were given by the autoinjector and 4 mg of naloxone were administered by the 4-mg Narcan spray device, while AUC values were lowest after 2 or 4 mg of naloxone were delivered by the INND.

The relative bioavailability of the intranasal naloxone compared with the intramuscular device was 54%-62% for the Narcan spray devices versus only 19%-23% using the INND.

Exposure during the critical first five, 10, and 20 minutes was approximately two- to three-fold higher using either Narcan spray device or the autoinjector compared with exposure following use of the INND.

"Using the FDA-approved nasal Narcan spray is a great choice for average consumers, who will likely keep only one or two devices on hand," Dr. Krieter said. "It is smaller, easier to use, and doesn't require much if any training to use properly. The Narcan spray is a ready-to-use device; the improvised device needs assembly, and lay persons may not able to use it correctly in a panic situation."

"Consumers can also consider the FDA-approved autoinjector, Ezvio, which also delivers the naloxone efficiently," he said. "A generic version will be available later this year for some purchasers. It is important to check with your pharmacist about cost options and potential insurance coverage before making these purchases."

Dr. Krieter added, "Physicians and pharmacists should caution patients - and their friends and family members - that the FDA-approved nasal spray device delivers more naloxone to the bloodstream than the improvised nasal spray device."

Dr. Jermaine Jones from Columbia University Medical Center and New York State Psychiatric Institute, in New York City, recently showed that patients who use opioids can be trained to respond appropriately to opioid overdoses. He told Reuters Health by email, "Although there are statically significant differences in pharmacokinetics, whether these translate to clinically significant differences in the ability of each product to reverse an overdose is unknown. A clinical research study among opioid-dependent samples is needed to gather this information."

"Physicians should note the increased range of products available to their patients to mitigate the risk of opioid overdose," said Dr. Jones, who was not involved in the new work. "The FDA-approved formulations work best and almost equivalently well. For those treating substance use disorder populations, providing the (Narcan spray) product should be standard clinical practice."

Dr. Jones doesn't think it's time to abandon the INND, though. He said, "We know that the INND is effective at reversing opioid overdoses, because, for years, it was the only game in town for peer-based naloxone programs."

Dr. William Eggleston from Binghamton University School of Pharmacy and Pharmaceutical Sciences, in Binghamton, and SUNY Upstate Medical University, in Syracuse, New York, told Reuters Health by email, "The results of this study further support that nasal naloxone is a reasonable alternative for individuals with limited or no medical training. In addition to these findings, our own research has shown that community members are able to successfully administer nasal naloxone more rapidly than INNDs. These devices should be considered first-line options for community based programs."

"INNDs may still have a place in overdose reversal, but their potential limitations must be considered," he said. "These results showed a lower blood naloxone level after INND use, but the clinical significance of this difference is unknown."

"It is worth adding that there are many unpredictable factors that can cause these antidotes to fail, and emergency services should also be contacted for a suspected overdose even if naloxone is successfully used," Dr. Eggleston said.

SOURCE: https://bit.ly/2uAG64t

J Clin Pharmacol 2019.

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