FDA Panel Gives Unanimous Thumbs Up to OTC Naloxone

Pauline Anderson

February 16, 2023

In the wake of an escalating opioid crisis, members of a joint Food and Drug Administration (FDA) advisory committee gave the green light to an over-the- counter (OTC) version of prescription naloxone nasal spray, an opioid overdose reversal agent.

Every member of the Nonprescription Drugs Advisory Committee (NDAC) and the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) agreed that the evidence of benefits from switching the drug to OTC status far outweighs the minimal risks.

"The unanimity of the committee is a profound statement about how important this is," voting member Jeffrey Brent, MD, PhD, distinguished clinical professor of medicine and emergency medicine, University of Colorado, Aurora, said during the meeting.

The "overwhelming positive support" for an OTC naloxone "underscores the importance of moving this drug to greater access and highlights the terrible risks of not acting in terms of making the drug more accessible," added meeting chair Maria C. Coyle, PharmD, associate clinical professor at the Ohio State University College of Pharmacy, Columbus.

Urgent Need

During the NDAC and AADPAC meeting to discuss the New Drug Application submitted by Emergent BioSolutions, Inc., delegates heard details of a growing opioid crisis. Drug overdoses are now the leading cause of accidental deaths in the United States, with almost 1 million overdose deaths occurring since 1999 — and most of them opioid-related.

Naloxone (NARCAN) is an opioid antagonist for the emergency treatment of an opioid overdose. It is available as a prescription in several doses, strengths, dosage forms, and routes of administration. The NARCAN spray delivers a single 4 mg dose intranasally.

The prescription spray is the most commonly sold emergency treatment for opioid overdose in the US. It was approved in 2015 to treat a known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, in all ages. Since then, post-marketing data have supported the product's safety and efficacy.

Representatives from Emergent emphasized the urgent need for a naloxone product that nonhealthcare professionals can use in the community setting, where most opioid overdoses occur. Their proposed OTC naloxone is identical to the prescription version with respect to intranasal delivery, dose, formulation, product quality, and active pharmaceutical ingredient.

They stressed the product is easy to administer and does not require inhalation, assembly, or specialized training. They added that it's also easy to carry, store, and is needle-free — so there is no risk of needle-stick injury.

Meeting attendees also heard that the risks of naloxone nasal spray, which include withdrawal and vomiting, are manageable and the potential for misuse is minimal.

Having naloxone spray available OTC — for example from vending machines, convenience stores, supermarkets, and big box stores — would help overcome current barriers to accessing the drug, the representatives noted.

For example, some pharmacies choose not to stock naloxone, prescriptions require access to practitioners familiar with the drug, and current community distribution programs for naloxone are limited.

Labeling Issues

Easier access to naloxone could also reduce the shame and stigma experienced by people who use drugs, experts note.  

"A key component of our addressing the ongoing opioid crisis will be broadening access to this medicine and decreasing the stigma associated with the purchase of naloxone," committee member Brian T. Bateman, professor and chair in the Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Palo Alto, California, said during the meeting.

The drug company conducted a simulated human factors validation (HFV) study with untrained users from various backgrounds, including some with limited literacy and adolescents. The study, which used a simulated emergency to assess how well consumers could follow the five steps on the package label, showed the product could be used safely and effectively.

However, some steps that appeared on the back of the package and on the side panel confused some study participants who started with step three (call 911) instead of first administering a dose after checking that there had been an overdose.

Some delegates noted the HFV study did not include adolescents younger than 15 years who might be called upon to aid a family member experiencing an overdose. There was also some question surrounding the number of study participants with low literacy and the labelling.

But committee members felt such issues should not get in the way of moving quickly to allow the drug to be accessed OTC.

Some noted label improvements, such as having the five steps on a single panel and in a font that facilitates easy reading, can be discussed later — as could the possible need for another HFV study, they said.

Supportive Evidence

FDA officials reiterated the goal of the agency to increase access to opioid overdose reversal agents, and to encourage acceleration of the development of nonprescription naloxone.

Meeting delegates also stressed the urgency of expanding access to a life-saving drug.

"All the evidence and data presented today is supportive of approving this drug to get to OTC, and hopefully we can leave today knowing that we are saving lives," said voting member Diane B. Ginsburg, PhD, clinical professor in the Pharmacy Practice Division and associate dean for healthcare partnerships at The University of Texas at Austin College of Pharmacy.

However, there was some concern about follow-up. "There's a moral imperative for the FDA to develop a program similar to its [Risk Evaluation and Mitigation Strategies] (REMS)," said Timothy J. Ness, MD, PhD, professor emeritus, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham.

Even though there is no regulatory requirement for such follow-up for nonprescription products, "I would encourage them to do a similar process to help with connection to care," Ness said.

At the end of the meeting, all 19 voting delegates agreed the benefit-risk profile of naloxone nasal spray supports its use as a nonprescription opioid overdose reversal agent.

FDA Advisory Committee Meeting. February 15, 2023.

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