FDA Approves Rx Nalmefene Nasal Spray to Reverse Opioid Overdose

The US Food and Drug Administration (FDA) on May 22 approved nalmefene (Opvee; Indivior PLC) nasal spray for the emergency treatment of opioid overdose, either known or suspected, caused by natural or synthetic opioids, in adults and pediatric patients aged ≥12 years.

This is the first FDA approval of nalmefene hydrochloride nasal spray. The prescription product delivers 2.7 mg of the drug into the nasal cavity and is intended for use in health care and community settings. In its public announcement,¹ Indivior said it expects the nasal spray to be available in the fourth quarter of this year.

The FDA’s approval is based on a unique pharmacodynamic study, according to the statement, a clinical model of opioid-induced respiratory depression that evaluated the effect of 2.7 mg nalmefene on remifentanil-induced respiratory depression in 61 opioid-experienced, non-opioid-dependent participants.

The study demonstrated that following nalmefene administration time to onset of reversal of respiratory depression was between 2.5 and 5 minutes and full recovery of respiratory drive was observed as early as 5 minutes following administration. The terminal plasma half-life of the opioid receptor antagonist has been determined as approximately 11 hours, comparable to that of most opioids, including fentanyl, the company said.

“In the 12-month period ending in December 2022, over 79,000 people in the US were reported to have died of an opioid overdose, of which 90% – approximately 72,000 – were linked to illicit synthetic opioids, mainly fentanyl.”

The rapid onset of effect and duration of action are “attributes well-suited to address the challenges of today’s opioid overdose crisis,” the company said, emphasizing that the speed of onset of action, long duration, and high potency of accessible synthetic opioids including fentanyl have combined to drive unprecedented numbers of overdose deaths across a broader range of ages. Opioid overdose is now a leading cause of death for people aged 18 to 45 years, according to the group Families Against Fentanyl. Moreover, estimates are that for each opioid-induced fatality, there are an additional 6.4-8.4 overdoses that are not fatal but that may lead to long-term physician and mental impairment.

The most common adverse reactions included headache, nausea, nasal discomfort, nasal congestion, fatigue, anxiety, hot flush, erythema, decreased appetite, and vomiting. Invidior also emphasizes that while the duration of action of nalmefene matches that of most opioids, respiratory depression may recur, requiring continued surveillance of the affected patient and possible repeat administration of nalmefene, using a new nasal spray cannister.

“The agency continues to advance the FDA Overdose Prevention Framework and take actionable steps that encourage harm reduction by supporting the development of novel overdose reversal products,” said FDA Commissioner Robert M. Califf, MD. “On the heels of the FDA’s recent approval of the first over-the-counter opioid reversal agent, the availability of nalmefene nasal spray places a new prescription opioid reversal option in the hands of communities, harm reduction groups and emergency responders.”

Reference: Indivior announces U.S. Food and Drug Administration approval of OPVEE® (NALMEFENE) nasal spray, an opioid overdose rescue medicine for natural and synthetic opioids like fentanyl. Invidior PLC. May 22, 2023. Accessed May 23, 2023.