FDA Approves the First Over-the-Counter Naloxone Nasal Spray (2023)

Table of Contents

1. What the FDA Did
2. What Naloxone Is
3. What “Over the Counter” Means: the Rx-to-OTC Switch
4. The Steps Before the Approval
5. The Evidence the FDA Relied On
6. What Changed for Other Naloxone Products
7. The Risk the FDA Described
8. Why the FDA Acted: the Overdose Figures
9. What the Approval Does Not Do
10. Dates and Legal Status as of 18 October 2026
11. How the Approval Fits Other FDA Actions
12. Primary Documents
13. Key Research Papers
14. Connections
15. Featured Videos

1. What the FDA Did

The FDA news release of 29 March 2023, “FDA Approves First Over-the-Counter Naloxone Nasal Spray,” carries the subtitle “Agency Continues to Take Critical Steps to Reduce Drug Overdose Deaths Being Driven Primarily by Illicit Opioids.” It states that the agency approved a 4 mg naloxone hydrochloride nasal spray “for over-the-counter (OTC), nonprescription, use.”

The action changed the status of one already-approved product: a spray first approved by the FDA in 2015 as a prescription drug could now be sold without a prescription. The release says the action “paves the way for the life-saving medication to reverse an opioid overdose to be sold directly to consumers.”

The FDA Commissioner said in the release that the agency “has used its regulatory authority to facilitate greater access to naloxone by encouraging the development of and approving an over-the-counter naloxone product to address the dire public health need,” and that the approval “will help improve access to naloxone, increase the number of locations where it’s available and help reduce opioid overdose deaths throughout the country.” The Commissioner also said the agency encouraged the manufacturer to make the product available “as soon as possible and at an affordable price.”

The Director of the FDA’s Center for Drug Evaluation and Research (CDER) called naloxone “a critical tool in addressing opioid overdoses” and said the agency was “working with our federal partners to help ensure continued access to all forms of naloxone during the transition of this product from prescription status to nonprescription/OTC status.”

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2. What Naloxone Is

The release describes naloxone as “a medication that rapidly reverses the effects of opioid overdose and is the standard treatment for opioid overdose.”

The FDA’s information page on overdose-reversal drugs, which the release lists under “Related Information,” adds three points. Naloxone is “a lifesaving emergency treatment that reverses opioid overdose.” It is “a medicine with no abuse potential, and it is not a controlled substance” — and it it “can also be administered by individuals with or without medical training.”

The FDA’s April 2023 safety communication on opioid pain medicines describes naloxone as “an opioid reversal medicine used to treat an opioid overdose or possible overdose” that “can help prevent death.”

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3. What “Over the Counter” Means: the Rx-to-OTC Switch

The FDA’s page on prescription-to-nonprescription switches explains that the company holding a prescription drug’s approval (its “sponsor”) may ask to change its marketing status through the new drug application (NDA) process — a change “commonly referred to as a Prescription-to-Nonprescription (RX-to-OTC) switch.”

• What the sponsor has to show. According to the FDA page, a switch application contains efficacy and safety data showing the drug is safe to use in the nonprescription setting, and “the applicant must provide data that demonstrate consumers can understand how to use the drug safely and effectively without the supervision of a healthcare professional.” Post-marketing safety surveillance data are also required.
• The legal test. The FDA approves a switch when it determines that the prescription requirement is “not necessary for the protection of the public health by reason of the drug’s toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use,” and that “the drug is safe and effective for use in self-medication as directed in proposed labeling” (21 CFR 310.200(b)).

The March 2023 release says the manufacturer of the spray followed this process: it “provided data demonstrating that the drug is safe and effective for use as directed in its proposed labeling” and “also showed that consumers can understand how to use the drug safely and effectively without the supervision of a healthcare professional.”

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4. The Steps Before the Approval

The FDA documents give this sequence:

• 2015. The nasal spray is first approved by the FDA as a prescription drug.
• 2019. The FDA announces that it has “designed, tested, and validated a model naloxone Drug Facts Label (DFL) with easy-to-understand pictograms on how to use the drug,” to encourage manufacturers to pursue nonprescription naloxone.
• 16 November 2022. In a Federal Register notice (87 FR 68702, Docket No. FDA-2022-N-2673) the FDA announces its “preliminary assessment that certain types of naloxone hydrochloride (‘naloxone’) drug products may be approvable as safe and effective for nonprescription use.” Its preliminary opinion covered naloxone nasal spray up to 4 mg and naloxone autoinjector for injection into a muscle or under the skin up to 2 mg. The notice says the prescription requirement for these products “might not be necessary for the protection of the public health,” but that the agency needed more data, “such as product-specific data on the nonprescription user interface design, including packaging and labeling,” to decide. Comments were accepted until 17 January 2023.
• 9 January 2023. A Federal Register notice (88 FR 1235, Docket No. FDA-2022-N-3245) announces a joint meeting of two expert panels, the Nonprescription Drugs Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee, and opens a public docket for comments. A Federal Register docket is the public file that holds such comments and meeting materials.
• 15 February 2023. The joint meeting is held virtually. According to the March release, committee members “voted unanimously to recommend it be approved for marketing without a prescription.”
• 29 March 2023. The FDA approves the spray for nonprescription use.

The release also notes that the application “was granted priority review status.”

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5. The Evidence the FDA Relied On

The release names two pieces of evidence beyond the drug’s existing record of safety and effectiveness as a prescription product:

• The model Drug Facts Label. The pictogram-based label that the FDA itself had designed, tested and validated in 2019 “was used to support the approved application.”
• A simulated-use human factors validation study. The release describes this as a study “designed to assess whether all the components of the product with which a user would interact could be used safely and effectively as intended.”

These match the gap the November 2022 notice had identified: the agency had said it needed product-specific data on the nonprescription “user interface design, including packaging and labeling.”

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6. What Changed for Other Naloxone Products

• Generic 4 mg nasal sprays. The release says the approval “will require a change in the labeling for the currently approved 4 mg generic naloxone nasal spray products that rely on [this product] as their reference listed drug.” Makers of those generics “will be required to submit a supplement to their applications to effectively switch their products to OTC status.”
• Other brand-name sprays of 4 mg or less. The approval “may also affect the status of other brand-name naloxone nasal spray products of 4 mg or less,” but the release says such determinations “will be made on a case-by-case basis.”
• Why one product’s switch affects others. The November 2022 notice explains that the Federal Food, Drug, and Cosmetic Act “does not permit the simultaneous marketing of the same drug with the same active ingredient as both a prescription and nonprescription product, absent a clinically meaningful difference between them.” It stated that once a nonprescription naloxone product was approved, currently marketed naloxone products labeled “Rx only” with no clinically meaningful difference from it “will be considered misbranded.”
• Everything else stays prescription. “Other formulations and dosages of naloxone will remain available by prescription only,” according to the release.

The CDER Director added that the agency “will work with any sponsor seeking to market a nonprescription naloxone product, including through an Rx to OTC switch.”

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7. The Risk the FDA Described

The release states one specific risk. In people who are opioid dependent — whose bodies have adapted to regular opioid use — use of the spray “may result in severe opioid withdrawal.” The FDA lists the signs as:

• body aches, shivering or trembling, and weakness;
• diarrhea, nausea or vomiting, and abdominal cramps;
• increased heart rate (tachycardia) and increased blood pressure;
• fever, runny nose, sneezing, goose bumps, sweating and yawning;
• nervousness, restlessness or irritability.

The release does not describe any other safety finding for the nonprescription product.

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8. Why the FDA Acted: the Overdose Figures

The release frames the approval within what it calls “a major public health issue in the United States,” stating that there were “more than 101,750 reported fatal overdoses occurring in the 12-month period ending in October 2022, primarily driven by synthetic opioids like illicit fentanyl.”

The release places the approval within the FDA Overdose Prevention Framework, whose priorities, as listed there, are “supporting primary prevention by eliminating unnecessary initial prescription drug exposure and inappropriate prolonged prescribing; encouraging harm reduction through innovation and education; advancing development of evidence-based treatments for substance use disorders; and protecting the public from unapproved, diverted or counterfeit drugs presenting overdose risks.”

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9. What the Approval Does Not Do

• It does not make every naloxone product nonprescription. Only the 4 mg nasal spray was approved for OTC use; “Other formulations and dosages of naloxone will remain available by prescription only.” Generic 4 mg sprays needed their own labeling supplements, and other brand-name sprays were left to case-by-case decisions.
• It does not set the price or the date of sale. “The timeline for availability and price of this OTC product is determined by the manufacturer,” the release says, and the switch “may take months.”
• It does not end prescription access. The FDA’s April 2023 safety communication on opioid pain medicines states that “Prescription and non-prescription forms of naloxone are FDA approved.”
• It does not reverse non-opioid drugs. Naloxone works on opioids. The FDA’s November 2022 alert on xylazine, a veterinary sedative found in the illicit drug supply, warned that naloxone may not reverse xylazine’s effects; that alert is reported on the site’s xylazine import page. The March 2023 release itself does not discuss xylazine.

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10. Dates and Legal Status as of 18 October 2026

• First approved as a prescription drug: 2015.
• Model naloxone Drug Facts Label announced: 2019.
• Preliminary assessment published: 16 November 2022 (87 FR 68702); comments closed 17 January 2023.
• Advisory committee meeting notice: 9 January 2023 (88 FR 1235).
• Joint advisory committee meeting: 15 February 2023 (unanimous vote for nonprescription marketing).
• Nonprescription approval: 29 March 2023.

Status as of 18 October 2026: final and in effect. Later FDA documents treat the approval as standing. The FDA’s 13 April 2023 safety communication on opioid pain medicines refers to the March 2023 approval of a naloxone nasal spray “to be sold over-the-counter without a prescription,” and the FDA’s information page on overdose-reversal drugs (content current as of 8 August 2024) states that the FDA “approved the first over-the-counter naloxone nasal spray in March 2023.” The FDA’s 2025 opioid safety communication, reported on the site’s 2025 opioid labeling page, states that naloxone is available over the counter and by prescription. A check of the Federal Register through 18 October 2026 found no FDA document withdrawing or limiting this nonprescription approval.

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11. How the Approval Fits Other FDA Actions

The release presents the approval as one of “a series of measures to help facilitate access to naloxone products,” following the 2019 model label and the November 2022 preliminary assessment. The FDA’s information page lists related agency activity, including a November 2022 stakeholder call on naloxone access and harm reduction programs, and a March 2023 stakeholder call “to discuss next steps for nonprescription naloxone following the first nonprescription naloxone approval.” The same page reports that the FDA approved the first nalmefene hydrochloride nasal spray to reverse opioid overdose in May 2023; the page describes nalmefene as “an opioid receptor antagonist” and says that product “is available by prescription.”

On 13 April 2023, the FDA announced required safety labeling changes for all opioid pain medicines. That communication tells health care professionals to “discuss the availability of naloxone” with all patients prescribed opioid pain medicines and to consider prescribing it to those at increased risk of overdose. That action is reported on the site’s 2023 opioid labeling page, and its 2025 follow-up on the 2025 opioid labeling page. Other 2023 drug actions on the site include the xylazine import restriction and the boxed warning on prescription stimulant misuse. In July 2023 the FDA also approved the first nonprescription daily birth control pill, another prescription-to-nonprescription switch.

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12. Primary Documents

1. U.S. Food and Drug Administration (2023). FDA Approves First Over-the-Counter Naloxone Nasal Spray. FDA News Release, 29 March 2023 — fda.gov news release
2. Food and Drug Administration, HHS (2022). Safety and Effectiveness of Certain Naloxone Hydrochloride Drug Products for Nonprescription Use; Request for Comments. Federal Register 87:68702–68713, 16 November 2022. Docket No. FDA-2022-N-2673 — FR Doc. 2022-24874
3. Food and Drug Administration, HHS (2023). Joint Meeting of the Nonprescription Drugs Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments. Federal Register 88:1235–1237, 9 January 2023. Docket No. FDA-2022-N-3245 — FR Doc. 2023-00110
4. U.S. Food and Drug Administration. Prescription-to-Nonprescription (Rx-to-OTC) Switches. Drug Application Process for Nonprescription Drugs, content current as of 21 May 2026 — fda.gov Rx-to-OTC switches page
5. U.S. Food and Drug Administration. Information about Naloxone and Nalmefene. Postmarket Drug Safety Information for Patients and Providers, content current as of 8 August 2024 — fda.gov naloxone and nalmefene page
6. U.S. Food and Drug Administration (2023). FDA updates prescribing information for all opioid pain medicines to provide additional guidance for safe use. Drug Safety Communication, 13 April 2023 — fda.gov drug safety communication
7. U.S. Food and Drug Administration. Food and Drug Administration Overdose Prevention Framework — fda.gov Overdose Prevention Framework

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Key Research Papers

1. Walley AY, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A (2013). Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ 346:f174 — PubMed PMID: 23372174
2. Krieter P, Chiang N, Gyaw S, Skolnick P, Crystal R, Keegan F, Aker J, Beck M, Harris J (2016). Pharmacokinetic properties and human use characteristics of an FDA-approved intranasal naloxone product for the treatment of opioid overdose. Journal of Clinical Pharmacology 56(10):1243-1253 — PubMed PMID: 27145977
3. Saari TI, Strang J, Dale O (2024). Clinical pharmacokinetics and pharmacodynamics of naloxone. Clinical Pharmacokinetics 63(4):397-422 — PubMed PMID: 38485851
4. Evoy KE, Hill LG, Davis CS (2021). Considering the potential benefits of over-the-counter naloxone. Integrated Pharmacy Research & Practice 10:13-21 — PubMed PMID: 33623754
5. Carpenter DM, Marley GT, Annis IE, Delamater P, Egan KL (2025). Over-the-counter naloxone availability at North Carolina community pharmacies: a secret shopper study. Drug and Alcohol Dependence 267:112545 — PubMed PMID: 39756348
6. Loera LJ, Lines JE, Mayberry SR, Hilzendager SA, Ferguson AP, Hill LG (2025). Over-the-counter naloxone and nonprescription syringe availability in community pharmacies. JAMA Network Open 8(2):e2458095 — PubMed PMID: 39899298
7. Eldridge LA, Kline D, Fields K, Lewis B, McMillian J 3rd, Graves RL, Egan KL (2026). Availability of naloxone in retail pharmacies following introduction of over-the-counter status. JAMA Network Open 9(7):e2623617 — PubMed PMID: 42467434

The first paper studies community overdose education and nasal naloxone distribution in Massachusetts communities; the second describes how a 4 mg intranasal naloxone product is absorbed and how people used it; the third is a review of how naloxone acts in the body; the fourth discusses the case for nonprescription naloxone before the switch; the last three examine whether pharmacies actually stocked naloxone after it became available over the counter.

PubMed Topic Searches

1. PubMed: over-the-counter naloxone
2. PubMed: intranasal naloxone and opioid overdose
3. PubMed: naloxone pharmacy access

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Connections

• FDA Actions of 2023
• FDA and Regulation
• Opioid Overdose
• Addiction and Substance Use Disorders
• Respiratory Failure
• Opioid Pain Medicine Label Updates (2023)
• Xylazine Import Restriction (2023)
• Stimulant Misuse Boxed Warning (2023)
• Over-the-Counter Daily Birth Control Pill (2023)
• Nasal Epinephrine for Anaphylaxis (2024)
• Tianeptine Retailer Warning (2024)
• Opioid Long-Term Use Label Changes (2025)
• Concentrated 7-OH Kratom Products (2025)

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