FDA Approves Second Over the Counter Naloxone Nasal Spray

The FDA has approved Harm Reduction Therapeutics’ nonprescription RiVive (naloxone) 3.0 mg nasal spray for the emergency treatment of opioid overdose. RiVive will be made available for free or low cost, and company executives said in a press release that no company will profit from the product.

Harm Reduction Therapeutics said it will supply RiVive to communities that need it most and will make at least 200,000 doses available for free. ReVive, which is delivered as an atomized spray (0.1 ml) using a standard unit dose system for single administration, is expected to be available in early 2024.

Michael Hufford, Ph.D.

Michael Hufford, Ph.D., co-founder & CEO, said it costs $36 to manufacture and package each twin pack of RiVive. "That price also allows us to give 10% of our inventory away free (approximately 100,000 twin packs in year 1)," he told Formulary Watch. "As partners step forward with charitable donations, that will enable us to reduce the cost of RiVive, and/or give more of it away for free."

He said they are working with partners to help ensure that the free doses go to those in greatest need, especially those harm reduction organizations that have been paying premium prices for years for intranasal naloxone products.

Drug overdose continues to be a major public health issue in the United States. In the 12-month period ending in February 2023, more than 105,000 reported fatal overdoses occurred which were primarily driven by synthetic opioids like illicit fentanyl, according to the FDA. And since 2017, more than 290,000 people across the United States have died of an opioid overdose, according to the National Institute on Drug Abuse.

Robert M. Califf, M.D.

“We know naloxone is a powerful tool to help quickly reverse the effects of opioids during an overdose. Ensuring naloxone is widely available, especially as an approved OTC product, makes a critical tool available to help protect public health,” FDA Commissioner Robert M. Califf, M.D., said in a separate press release.

The approval of RiVive was supported by data from a study that showed similar levels of RiVive reach the bloodstream as an approved prescription naloxone product. The drug has been demonstrated to be safe and effective for use as directed in its labeling. The use of RiVive nasal spray in those who are dependent on opioids may result in severe opioid withdrawal, including shaking, sweating and nausea.

RiVive is currently being produced under a commercial supply agreement with Catalent, a contract manufacturing organization, at its facility in Morrisville, N.C.

Harm Reduction Therapeutics will receive up to $9 million in additional financial support from Purdue Pharma’s bankruptcy settlement for ReVive’s commercial readiness, Harm Reduction said earlier this year.

In March 2023, the FDA approved the first nonprescription naloxone to Emergent BioSolutions’ Narcan 4 mg (naloxone hydrochloride) nasal spray. The application to approve Narcan nasal spray for OTC use was granted priority review status and was the subject of an advisory committee meeting in February 2023, where committee members voted unanimously to recommend it be approved for marketing without a prescription.

FDA officials said they would work with any sponsor seeking to market a nonprescription naloxone product, including through an Rx to OTC switch. Last year, the FDA issued an assessment that aims to encourage the development of OTC naloxone products. The agency indicated that up to 4 mg nasal spray and up to 2 mg autoinjector for intramuscular or subcutaneous use may be approvable as safe and effective for nonprescription use.