FDA Advisors Endorse Moving Naloxone Over the Counter

Advisors to the FDA unanimously recommended the agency approve the first over-the-counter (OTC) naloxone (Narcan) product, though many committee members expressed continued concern about user instructions for the opioid overdose reversal drug.

By a vote of 19-0 on Wednesday, members of both the Nonprescription Drug Advisory Committee and Anesthetic and Analgesic Drug Products Advisory Committee said the impressive safety and risk-benefit profile support approval of the nonprescription naloxone spray, which would allow for an unprecedented expansion of access.

"I think the unanimity of the committee is a very profound statement about how important this is," said Jeffrey Brent, MD, PhD, of the University of Colorado School of Medicine in Aurora.

"This is a very important step from a public health perspective," said Brian Bateman, MD, MSc, of Stanford University School of Medicine in California. "A key component of our addressing the ongoing opioid crisis will be broadening community access to this medication and decreasing the stigma associated with the purchase of naloxone."

"We know from long experience that this is a safe and effective medication," he added. "So there's very little reason not to move it to an over-the-counter status."

Emergent BioSolutions presented data on the safety profile of the product as well as newly developed labeling for an OTC form of its nasal naloxone spray, a product the FDA approved in 2015 via prescription for emergency situations involving suspected opioid overdose. The single-dose nasal spray device contains 4 mg of naloxone hydrochloride in a 0.1 mL aqueous solution.

Advisors determined that the risk-benefit profile supported nonprescription use of the single-dose product. They did express some concerns about the clarity of the instruction labels present by the company and the FDA, however.

Data shared from two studies that accessed the efficacy of the labeling -- a label comprehension study and a human factors validation study -- showed that the instructions did not lead to optimal outcomes in all endpoints. Primary endpoints in the label comprehension study included properly conducting various steps in a certain order: checking for a suspected overdose, giving the initial dose of naloxone, calling 911 immediately, repeating doses every few minutes until the person is fully awake or until emergency personnel arrive, staying with the person until emergency personnel arrive.

In particular, participants in both studies found the instruction label to be confusing to follow and failed to complete each step in the proper order. For example, some people said they would call 911 before administering a dose, or would wait to see if the person woke up after the first dose before calling 911.

The company and the FDA presented multiple versions of possible drug fact labels for the advisors' consideration, but the advisors did not believe the need for better data and design on the labeling outweighed the need for making OTC naloxone available as soon as possible.

While committee members suggested several potential labeling changes, they ultimately decided to leave the final design to the FDA's discretion. Many advisors called for a postmarketing follow-up human factor validation study to help determine potential changes to the labeling in the future.

"There's room for iterative work on improving the label, and additional human factor studies might be conducted in the future," Bateman said, but added that "perfect shouldn't be the enemy of the good."

In a pre-meeting briefing document for the advisors, FDA reviewers highlighted that more than a million people have died from drug overdoses in the past two decades, and noted that deaths are on the rise, with a 17% increase from 2020 to 2021 based on recent CDC data.

Several commenters and advisors shared personal stories that reflected the widespread impact of drug overdose deaths. Committee member Michael Sprintz, DO, founder of Sprintz Center for Pain in Shenandoah, Texas, shared his own personal story.

"In addition to being a pain doctor and an addiction doctor, I've also been in sobriety from opioid use disorder for 22 years," Sprintz said. "The evidence is compelling that the benefits clearly outweigh the risks and the urgency is definitely paramount right now."

"I actually had a friend who lost her 19-year-old son about 4 days ago," he added. "So I think it's a wonderful thing that we did today."

Jordan Marie Ballou, PharmD, of the University of South Carolina College of Pharmacy in Columbia, shared in that sentiment about the importance of the panels' recommendation for individuals all around the country.

"My vote is a 'yes' for persons with opioid use disorder," Ballou said. "And it is a 'yes' for people who love those people and their ability to care for them should the need ever arise."

While the FDA is not required to follow the recommendations of its advisory committees, it typically does.

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