FDA Taking Steps to Approve OTC Naloxone for Opioid Overdose

FDA Taking Steps to Approve OTC Naloxone for Opioid Overdose
Connie Khong, PharmD
Pharmaceutical Care First-Year Leadership Resident - Smiley’s Clinic

In November 2022, the United States Food and Drug Administration (FDA) issued a Federal Register notice. The notice included an assessment revealing specific naloxone drug products (naloxone 4 mg nasal spray and naloxone 2 mg auto-injector for intramuscular or subcutaneous use) may be safe and effective for use without a prescription. This announcement was another support measure taken by the FDA to combat the ongoing opioid epidemic, with hopes to increase the accessibility of naloxone with the development and approval of over-the-counter (OTC) naloxone. 

As the assessment is preliminary, the next step in the process of OTC naloxone approval is for the FDA to collect data demonstrating the safety and efficacy of additional naloxone products not included in the original assessment. This would encompass products supplied as naloxone vials, ampules, and syringes, and the recently approved higher-dosed naloxone products (KLOXXADO, an 8 mg, prefilled, single-dose nasal spray, and ZIMHI, a 5 mg single-dose, prefilled syringe with an integrated needle for intramuscular or subcutaneous administration). In addition, the FDA asked for comments from the public discussing the impact of switching naloxone from prescription to non-prescription status. Comments were submitted electronically (Safety and Effectiveness of Certain Naloxone Hydrochloride Drug Products for Nonprescription Use) or written and mailed. The comment period ended January 17, 2023, 11:59 PM Eastern Time, with mailed comments being considered on time if received on or before January 17, 2023.

Other actions taken by the FDA include providing guidance to harm-reduction programs on distributing naloxone, exempting some of the requirements of the Drug Supply Chain Security Act, increasing the shelf-life of naloxone, and developing a Drug Facts Label for naloxone. Drug Facts labels are required for OTC products, and the development of such a label specific to naloxone was created in hopes of encouraging manufacturers to pursue OTC approval of naloxone. The FDA has also required that manufacturers of opioid analgesics and medications used to treat opioid use disorder include recommendations related to naloxone use in their prescribing information. In the future, the FDA intends to implement the FDA Overdose Prevention Framework. Its vision is aimed at preventing opioid overdoses and reducing deaths through four priorities to address this public health emergency. More about the framework can be found here.


  1. Brooks, M. FDA Takes New Steps to Support OTC Naloxone for Opioid Overdose. Medscape. Published November 15, 2022. Accessed November 16, 2022. https://www.medscape.com/viewarticle/984088 
  2. United States Food and Drug Administration. FDA Announces Preliminary Assessment that Certain Naloxone Products Have the Potential to be Safe and Effective for Over-the-Counter Use. Published November 15, 2022. Accessed December 13, 2022. https://www.fda.gov/news-events/press-announcements/fda-announces-preliminary-assessment-certain-naloxone-products-have-potential-be-safe-and-effective 
  3. United States Food and Drug Administration. Safety and Effectiveness of Certain Naloxone Hydrochloride Drug Products for Nonprescription Use; Request for Comments. Federal Register. Published November 16, 2022. Accessed December 13, 2022. https://www.federalregister.gov/documents/2022/11/16/2022-24874/safety-and-effectiveness-of-certain-naloxone-hydrochloride-drug-products-for-nonprescription-use