FDA Approves Second Generic OTC Naloxone Nasal Spray to Reverse Opioid Overdose

The FDA has approved a second generic equivalent to over-the-counter (OTC) nonprescription Narcan HCl Nasal Spray 4 mg following its review of an abbreviated new drug application (ANDA) from Amneal Pharmaceuticals for the company’s OTC naloxone hydrochloride nasal spray, USP, 4 mg for the emergency treatment of opioid overdose.¹

Naloxone hydrochloride binds to opioid receptors, blocking activation and can restore breathing within 2 to 3 minutes, even if breathing has stopped. _{^{(©Hanson/stock.adobe.com)}}

Amneal announced the approval in an April 24, 2024, news release that also said the product is now available in the US.¹

Narcan HCI Nasal Spray 4 mg was approved in March 2023 for nonprescription, over-the-counter use.² In July, the FDA approved a second branded naloxone HCl nasal spray at a dose of 3 mg, RiVive, awarding the indication to Harm Reduction Therapeutics.³ FDA also approved the first generic OTC naloxone nasal spray in July based on the agency’s review of the supplemental ANDA submitted by Padagis US LLC.⁴

Naloxone HCl nasal spray is in wide use to help reverse drug overdose from prescription opioids, such as oxycodone and hydrocodone, and illicit versions including heroin and fentanyl. In 2023, the death rate from opioid overdose rose above 112 000 over a 12-month period for the first time, according to the Centers for Disease Control and Prevention.⁵ In 2022 more than two-thirds of drug overdose fatalities involved synthetic opioids like fentanyl, the drug responsible for more deaths of individuals younger than age 50 years than heart disease, cancer, homicide, suicide, or other accidents.⁶ In nearly half (46%) of overdose deaths there is another person present who has the potential to intervene.⁷

Naloxone HCI nasal spray, an opioid antagonist, rapidly reverses the effects of an opioid emergency by binding to opioid receptors and reversing or blocking the effects of the drug. Normal breathing is typically restored within 2 to 3 minutes, whether respiration has slowed or even stopped, according to the Amneal statement.¹

Amneal presents the OTC generic as an “affordable” alternative to Narcan and cites Iqvia data showing that commercial sales for the year ending in February 2024 were $266 million.¹ “Amneal is proud to help address this public health emergency by providing naloxone nasal spray at an affordable price and without a prescription,” Chirag and Chintu Patel, co-chief executive officers of Amneal said in the press announcement. “By enhancing access to naloxone nasal spray, we hope to get this affordable emergency treatment into the hands of even more people who could potentially save countless families and communities from further heartache and loss.”¹

"Through the FDA Overdose Prevention Framework, the agency remains focused on responding to all facets of substance use, misuse, substance use disorders, overdose and death in the US The framework’s priorities include: 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."

References

1. Amneal announces US FDA approval of over-the-counter naloxone hydrochloride nasal spray for emergency treatment of opioid overdose. News release. Amneal Pharmaceuticals. April 24, 2024. Accessed April 26, 2024. https://investors.amneal.com/news/press-releases/press-release-details/2024/Amneal-Announces-U.S.-FDA-Approval-of-Over-the-Counter-Naloxone-Hydrochloride-Nasal-Spray-for-Emergency-Treatment-of-an-Opioid-Overdose/default.aspx
2. Jennings S. FDA approves first OTC naloxone nasal spray for treatment of opioid overdoses. Patient Care. March 29, 2023. https://www.patientcareonline.com/view/fda-approves-naloxone-hydrochloride-nasal-spray-for-otc-nonprescription-use
3. Jennings S. FDA approves naloxone hydrochloride nasal spray for OTC, nonprescription use. Patient Care. July 31, 2023. https://www.patientcareonline.com/view/fda-approves-naloxone-hydrochloride-nasal-spray-for-otc-nonprescription-use
4. FDA approved second over-the counter naloxone nasal spray product. News release. US Food and Drug Administration. July 28, 2023. Accessed April 25, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-second-over-counter-naloxone-nasal-spray-product
5. Provisional drug overdose death counts. National Center for Health Statistics. Last reviewed April 17, 2024. Accessed April 25, 2024. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
6. Kariisa M, O’Donnell J, Kumar S, Mattson CL, Goldberger BA. Illicitly manufactured fentanyl-involved overdose deaths with detected xylazine - United States, January 2019–June 2022. MMWR Morb Mortal Wkly Rep. 2023; 72(26);721–727. https://www.cdc.gov/mmwr/volumes/72/wr/mm7226a4.htm#:~:text=In%202022%2C%20provisional%20data%20indicated,(IMFs)%20(1)
7. SUDORS dashboard: fatal overdose data. Drug overdose. Centers for Disease Control and Prevention. Updated February 26, 2024. https://www.cdc.gov/drugoverdose/fatal/dashboard/index.html