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Dr. Roach: Welcome to another episode of our podcast series, “Q&A with FDA”, from the FDA’s Division of Drug Information, where we answer some of the most frequently asked questions that we’ve received. In a previous episode, we discussed FDA’s Overdose Prevention Framework with Dr. Marta Sokolowska, Deputy Center Director for Substance Use and Behavioral Health in FDA’s Center for Drug Evaluation and Research. Today we are taking a deeper dive into one of the four key priorities of this framework: Encouraging Harm Reduction.

My name is Dr. Sara Roach. Today we are rejoined by Dr. Marta Sokolowska to discuss the Agency’s vision as it relates to encouraging harm reduction, including expanding availability and access to lifesaving overdose reversal products. We’re joined by Marta again to discuss the impacts of the recent approvals of nonprescription naloxone nasal spray as well as prescription nalmefene nasal spray, another medication for opioid overdose. Marta, thank you for joining us today, we are happy to have you back.

Dr. Sokolowska: Glad to be here!

Dr. Roach: I first want to discuss naloxone, since expanding access to naloxone has been one of FDA’s top priorities for years. There have been many activities to expand the availability of this lifesaving drug, the most recent being the approval of the first nonprescription naloxone nasal spray product in March of this year. We know that substance use disorders and overdoses are one of the most devastating public health crises affecting our country. Can you tell us how this approval will help those who are at risk for opioid overdose?

Dr. Sokolowska:

• As you said, we’ve prioritized widening access to opioid overdose treatments with focus on naloxone for many years.
• And when I spoke with your team last October, I mentioned that we were continuing to encourage and advise industry in the development of nonprescription naloxone, as well as working with industry regarding their efforts to bring novel and generic naloxone products to market.
• We had heard the calls from harm reduction programs and many other stakeholders to broaden naloxone access through availability of nonprescription naloxone.
• We’re proud to say that approval of nonprescription naloxone is now a reality.
• This approval of nonprescription Narcan 4 mg nasal spray paves the way for this life-saving medication to be sold directly to consumers in places like drug stores, convenience stores, grocery stores and gas stations, as well as online, without a prescription. This action should make it easier for harm reduction programs to distribute naloxone directly to persons who might use it.
• Dr. Roach: This is a huge step for making naloxone available in a variety of ways. When can consumers anticipate seeing naloxone on the over-the-counter shelves?

Dr. Sokolowska:

• It will take some time for nonprescription Narcan to be available on retail shelves. Timing for when nonprescription Narcan will be available for purchase will be determined based largely on operational logistics of the manufacturer and retailers. In the interim, remaining stocks of prescription-labeled Narcan, 4 milligram (mg) naloxone hydrochloride nasal spray, and other forms of naloxone, can still be obtained by a prescription or through state naloxone access laws, such as standing orders that enable individuals access to prescription forms of naloxone without a patient-specific prescription.
• In the immediate future, when discussing nonprescription naloxone, you will likely hear the term “transition” or “transition period.”
• While this is not a formal term or designated time period, the term “transition” or “transition period” typically refers to the time needed to implement an over-the-counter switch, or OTC switch.
• I want to be very clear: The approval of nonprescription naloxone does NOT mean that you will see prescription Narcan nasal spray being removed from the market immediately.
• Once the nonprescription version of Narcan nasal spray is available, remaining stocks of the prescription version will be phased out.

Dr. Roach: I want to circle back to when you specified Narcan 4 mg nasal spray. I understand naloxone comes in different formulation and dosages but at this time, only Narcan 4mg nasal spray is approved for nonprescription use. When can consumers expect other naloxone products will become nonprescription?

Dr. Sokolowska:

• Yes, your understanding is correct. Of brand name naloxone products, only Narcan 4mg nasal spray is available as nonprescription.
• Now that brand name Narcan is approved, any generic products relying on Narcan nasal spray as their reference drug must submit their own application supplements to switch their products to nonprescription status, in order to continue marketing.
• At this time, we cannot provide insight into the possibility of or timing of approval of other potential nonprescription naloxone products, including a switch of other prescription naloxone products to nonprescription status.
• However, FDA will work with any sponsor seeking nonprescription status for new naloxone products or a switch of its prescription naloxone product and encourages sponsors to contact FDA as early as possible to initiate discussions.

Dr. Roach: While this approval will certainly eliminate some barriers to naloxone, what about concerns of insurance coverage for nonprescription naloxone? Is FDA working with other agencies to develop solutions to address the new cost-burdens that this approval and the ensuing switch to nonprescription status naloxone may produce for those who may need it but may now have to pay out-of-pocket to receive?

Dr. Sokolowska:

• That’s an important concern to address, so thank you for bringing it up.
• While FDA does not have authority regarding insurance coverage or naloxone pricing, we have been supporting the efforts of our federal partners and other stakeholders to help minimize any negative impacts on patient access during the transition.
• We are committed to helping ensure continued access to other approved forms of naloxone.

Dr. Roach: Thank you, Marta, for the overview of naloxone. I now want to pivot to the approval of nalmefene nasal spray, another recent approval for opioid overdose reversal. What is important to know about this product?

Dr. Sokolowska:

• Nalmefene nasal spray is indicated for opioid overdose in patients 12 years of age and older and was approved last month.
• Nalmefene was previously approved as an injection. However, this is the first FDA approval of nalmefene hydrochloride nasal spray for health care and community use.
• The approval of nalmefene nasal spray is an important step in supporting the development of overdose reversal agents and providing patients another option in addition to naloxone.

Dr. Roach: As I stated earlier, encouraging harm reduction is one of the four priorities in FDA’s Overdose Prevention Framework. What is the next step for expanding availability and access to lifesaving overdose reversal products?

Dr. Sokolowska:

• Approving nonprescription naloxone and prescription nalmefene are important steps forward for overdose prevention, but we know there is more to be done. We understand there are many outstanding questions regarding the implementation of the nonprescription switch of naloxone and availability of nonprescription naloxone.
• And as I mentioned before, we are supporting the efforts of our federal partners and other stakeholders to help minimize any negative impacts of naloxone nonprescription status on patient cost.
• In addition, we continue to gather information and engage with key stakeholders to inform our evolving response to an evolving overdose crisis.
• For example, in March of this year, we partnered with the Reagan-Udall Foundation to host a two-day public workshop to better understand fatal overdoses, with the goal of informing product development and overdose management.
• We heard the voices and perspectives of people who use drugs, their families, harm reduction groups, clinicians, academic researchers, and federal partners.
• Questions have emerged as to whether current naloxone dosing is adequate in the era of illicitly manufactured fentanyl or would higher initial doses be more effective in reversing respiratory depression.
• At the same time, we heard support for more titratable and selective overdose reversal agents for a milder or more gradual reversal as opposed to additional higher-dose naloxone options.
• We also heard support for devices for automated overdose detection and alerts, as well as for better ways to provide respiratory support outside of hospital setting.
• It was inspiring to hear an overview of treatments other than naloxone that are under development for opioid overdose reversal – both pharmacological and non-pharmacological.
• And we heard interest in both pre-use agents to prevent respiratory depression as well as post-use respiratory stimulants.
• A final theme was the potential difference in ideal naloxone dosing strategy in community settings versus in hospital setting.

Dr. Roach: Thank you, Marta, for providing your insights today. Is there anything else you would like to share with our audience?

Dr. Sokolowska:

• It was my pleasure to be here with you today. I hope listeners can agree when I say that every person who needs an overdose reversal medication should have access to it. Whether it is an opioid overdose caused by a prescription medicine or an illicit drug, anyone can help save the life of someone in need.
• We believe making naloxone available without a prescription will help expand access to naloxone in a significant way.
• I want to emphasize again that FDA continues to support increased access to approved prescription overdose reversal products.
• We hope that our naloxone-related Drug Supply Chain Security Act guidance, issued last September, helps to facilitate and expedite the distribution of prescription naloxone products to harm reduction programs. We will consider updating the guidance to clarify the exclusions and exemption requirements for nalmefene in an effort to expand access to overdose reversal medications.
• Further, we are discussing with states the potential impact of the OTC switch on state naloxone access laws that authorize dispensing of prescription naloxone via standing orders, without a patient-specific prescription, for individuals to continue broad access to prescription naloxone.
• We will continue to foster research and development of other overdose reversal agents in addition to naloxone and nalmefene.

Dr. Roach: FDA will continue to use science and data to inform our policies, initiatives, and activities, and will adapt our approaches as our understanding of this crisis evolves. For additional information, visit the Food and Drug Administration Overdose Prevention Framework webpage. Thanks for tuning in to “Q&A with FDA” podcast series. The full podcast and transcript of this recording is available at fda.gov/QAwithFDA. And if you have drug-related questions, reach out to us at [email protected].

Resources:

• Information about Naloxone and Nalmefene
• FDA Overdose Prevention Framework