FDA Approves Second OTC Naloxone for Opioid Overdose Management

Four months after approving the first over-the-counter (OTC) naloxone, the FDA has made another harm reduction tool available by supporting a second OTC Naloxone nasal spray, RiVive. The nasal spray delivers a single 3 mg dose of naloxone hydrochloride as a 0.1 mL atomized spray for known or suspected opioid overdose.

Overdose prevention and management has become a vital goal across the United States healthcare system, which the opioid epidemic has disproportionately impacted. The National Institute on Drug Abuse (NIDA), a subset of the NIH, notes that opioids have contributed to over 106,000 deaths between 1999 and 2021. Additionally, the CDC estimates that 75% of drug overdoses in 2022 involved an opioid.

Considering the potential harms of these drugs — and the high over-prescription rates perpetuated by pharmaceutical companies’ misinformation — many healthcare organizations have prioritized harm reduction. For example, the FDA has launched the Overdose Prevention Framework, which aims to reduce overdose rates. As part of the framework, the agency has made an effort to make overdose reversal medications more widely available.

“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,” said FDA Commissioner Robert M. Califf, MD, in the FDA release. “The agency has long prioritized access to naloxone products, and we welcome manufacturers of other naloxone products to discuss potential nonprescription development programs with the FDA.” 

According to a press release by Harm Reduction Therapeutics, the nonprofit pharmaceutical company that manufactures ReVive, the drug has been known to have a three-fold higher systemic exposure than injectable naloxone.

Additionally, the FDA notes that the company has submitted data proving the safety and efficacy of the medication when used as directed by the label. Harm Reduction Therapeutics also conducted evaluations to ensure that consumers could use the drug without the help of a licensed healthcare professional.

Despite the drug's safety and efficacy, potential side effects include body aches, diarrhea, tachycardia, fever, runny nose, anxiety, nausea, vomiting, irritability, hypertension, and abdominal cramps. However, these symptoms are more common in opioid-dependent patients who experience withdrawal when the opioid receptor antagonist is delivered.

Harm Reduction Pharmaceuticals anticipates that the drug will be available in the US starting in early 2024 as twin packs of two single-use sprays to be administered every 2–3 minutes until the recipient is awake. Beyond availability, through a commercial supply agreement with Catalent, the company hopes to make at least 200,000 doses available at no cost. 

“We are grateful that FDA granted RiVive approval so we can now achieve what most thought impossible and no other company has: broad delivery of a lower-cost nasal naloxone product without a prescription to save lives that could otherwise be lost to opioid overdose,” said Michael Hufford, PhD, co-founder, and chief executive officer of Harm Reduction Therapeutics, Inc., in the company’s press release.