New Study Examines Nalmefene Auto-Injector and Intranasal Naloxone for Reversal of Respiratory Depression Induced by Fentanyl in a Controlled Clinical Study

News > Health News

Audio By Carbonatix

9:00 AM on Monday, September 29

The Associated Press

STAMFORD, Conn.--(BUSINESS WIRE)--Sep 29, 2025--

A pharmacodynamic study sponsored by Purdue Pharma L.P. (“Purdue”), conducted in healthy moderately experienced opioid users (n = 24) using an opioid induced respiratory depression (OIRD) model, found that ZURNAI™ (nalmefene injection) reversed fentanyl-induced respiratory depression with a shorter time to onset and a longer duration of action than an existing standard-of-care treatment, intranasal (IN) naloxone. ZURNAI, an auto-injector delivering 1.5 mg of nalmefene intramuscularly (IM), has the same pharmacological mechanism of action as naloxone. 2,3,4,5 The findings, recently published in the peer-reviewed Journal of Clinical Pharmacology,1 help support ZURNAI as an important addition to existing opioid overdose reversal options in the community setting.

ZURNAI is indicated for the emergency treatment of known or suspected opioid overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression. 5 ZURNAI is intended for immediate administration as emergency therapy in settings where opioids may be present. ZURNAI is not a substitute for emergency medical care. ZURNAI is contraindicated in patients with a known hypersensitivity to nalmefene hydrochloride or any ingredient in the product. 5 Please see additional Important Safety Information below and Full Prescribing Information.

This single-center, randomized, crossover study was conducted to evaluate whether ZURNAI could reverse fentanyl-induced respiratory depression in an OIRD model with an onset and magnitude comparable to, or better than, the current standard-of-care treatment, IN naloxone. Meeting this standard was required to obtain FDA approval of ZURNAI. 3

"The ability of the ZURNAI auto-injector to work quickly and for an extended period of time makes it an important addition to current opioid overdose reversal treatments in community settings," said Julie Ducharme, BPharm, MSc, PhD, Vice President and Chief Scientific Officer. "Our team remains committed to advancing research that deepens scientific understanding of opioid antagonists and represents Purdue’s efforts to combat the opioid crisis and help save lives. This study supports the importance of having multiple evidence-based treatment options for delivery of naloxone and nalmefene to better address the evolving dynamics of the opioid crisis.”

While ZURNAI provides an additional option for the treatment of opioid overdose, including overdoses resulting from high doses of potent, long-acting synthetic opioids, caution should be used in patients who are known to be opioid-dependent. While precipitated withdrawal can occur with both naloxone and nalmefene, given its greater potency as an opioid receptor antagonist, nalmefene may carry a risk of prolonged precipitated withdrawal in individuals who are frequent users of opioids and are physically dependent on or tolerant to their effects. Health care providers should also be aware that a recurrence of respiratory depression is possible.

The study involved 24 participants with moderate (≥10 times within the previous year and ≥3 times within the previous 12 weeks) experience using opioids for nontherapeutic purposes. All participants received intravenous fentanyl infusions, carefully administered in a controlled clinical setting. The fentanyl infusion reduced their breathing rates by approximately 50 percent from baseline, safely simulating the respiratory depression that accompanies an opioid overdose. Under careful monitoring, each participant received either ZURNAI (nalmefene injection) or IN naloxone twice each in separate sessions under standardized conditions. Researchers closely tracked and analyzed minute volume (MV), which is the volume of air in liters breathed per minute, to evaluate how quickly and to what extent ZURNAI could reverse fentanyl-induced respiratory depression compared to naloxone. Other factors that were tracked included participants’ oxygen levels and vital signs.

Following administration of ZURNAI, the onset of reversal of respiratory depression was observed between 2.5 to 5 minutes. At five minutes post dose, participants showed an increase in breathing (MV) of 4.59 liters per minute, compared to an increase of 1.99 liters with standard IN naloxone. The effect of ZURNAI remained consistent at critical early timepoints, including at 10, 15, 20, and 30 minutes after administration. Nalmefene was absorbed into the bloodstream with a median time to peak concentration of 12.5 minutes versus a median of 40 minutes for IN naloxone.

In this pharmacodynamic study, ZURNAI showed higher mean plasma concentrations and an extended duration compared to IN naloxone 1. The study found the half-life for nalmefene to be 7.98 hours and the half life for naloxone to be 1.64 hours. Both nalmefene and naloxone treatments were tolerated with no serious treatment-emergent adverse events (TEAEs). The most commonly reported TEAEs were feeling hot, nausea, headache, taste distortion, and sensitivity to touch.

Limitations of the present pharmacodynamic study include that the reversal sessions were not of sufficient duration to reliably document the full time-course of reversal effects. Further, for safety and ethical considerations, this study was conducted in an experimental setting, where fentanyl was infused over an extended period and titrated to maintain consistent plasma concentrations. For these reasons, the study results may not reflect real-world outcomes related to opioid overdose.

While the most recent national outcome data available show a significant decline in overdose deaths, fentanyl and other synthetics continue to be the main driver of drug overdose deaths. 6 To address it, the National Institutes of Health supports the development of more potent and longer-acting opioid antagonists. 7

“We are encouraged by the results of this study and the opportunity to report these important data in peer-reviewed fashion,” said Craig Landau, MD, President and CEO of Purdue. “We look forward to introducing ZURNAI for use as appropriate in the community setting by health care professionals and lay-persons alike. Given the autoinjector format, we believe ZURNAI to be a valuable, lifesaving option for use in environments ranging from a hospital or clinic, schools, homes and other public places. Through our Public Health Initiatives, we remain committed to supporting individuals and communities in need by offering this additional opioid overdose reversal option.”

ZURNAI will be available in late 2025. Purdue will distribute the product for no profit as part of the Company’s commitment to help abate the opioid crisis.

Further research is needed to expand the understanding of ZURNAI in diverse real-world community settings.

INDICATIONS AND USAGE

ZURNAI is intended for immediate administration as emergency therapy in settings where opioids may be present.

ZURNAI is not a substitute for emergency medical care.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ZURNAI is contraindicated in patients known to be hypersensitive to nalmefene hydrochloride or to any other ingredients in the product.

WARNINGS AND PRECAUTIONS

Risk of Recurrent Respiratory and Central Nervous System Depression
A recurrence of respiratory depression is possible, therefore, keep the patient under continued surveillance and administer repeat doses of ZURNAI if necessary, using a new auto-injector with each dose while awaiting emergency medical assistance.

Risk of Limited Efficacy with Partial Agonists or Mixed Agonist/Antagonists
Reversal of respiratory depression by partial agonists or mixed agonists/antagonists such as buprenorphine and pentazocine, may be incomplete. Repeat doses of ZURNAI may be required.

Precipitation of Severe Opioid Withdrawal
The use of ZURNAI in patients who are opioid dependent may precipitate opioid withdrawal.

Abrupt postoperative reversal of opioid depression may result in adverse cardiovascular (CV) effects. These events have primarily occurred in patients who had preexisting CV disorders or received other drugs that may have similar adverse CV effects. Monitor these patients closely in an appropriate healthcare setting after use of ZURNAI.

In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying, and hyperactive reflexes. Monitor the patient for the development of the signs and symptoms of opioid withdrawal.

Risk of Opioid Overdose from Attempts to Overcome the Blockade
Attempts to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids may lead to opioid intoxication and death.

ADVERSE REACTIONS

Most common adverse reactions (>5%) are feeling hot, nausea, headache, dizziness, chills, vomiting, allodynia, palpitations, tinnitus, ear discomfort, feeling abnormal, burning sensation, hot flush, and irritability.

USE IN SPECIFIC POPULATIONS

Pregnancy
An opioid overdose is a medical emergency and can be fatal for the pregnant woman and fetus if left untreated. Treatment with ZURNAI for opioid overdose should not be withheld because of potential concerns regarding the effects of ZURNAI in the fetus.

Pediatric Use
The safety and effectiveness of ZURNAI for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, have not been established in pediatric patients younger than 12 years of age.

Geriatric Use
Clinical studies of nalmefene hydrochloride injection did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Please readFull Prescribing Information
To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1 888⁠-⁠726⁠-⁠7535, option 2, or FDA at 1⁠-⁠800⁠-⁠FDA⁠-⁠1088 or www.fda.gov/safety/medwatch.

Intended for healthcare professionals of the United States of America only.

About Purdue Pharma L.P.

Purdue Pharma and its subsidiaries develop, manufacture and market medications to meet the evolving needs of healthcare professionals, patients, and caregivers. Purdue and its subsidiaries focus on balancing innovative science with clinically effective, compassionate care. The Company’s goals are to serve patients who rely on its medicines, pursue public health initiatives intended to help abate the opioid crisis, advance its pipeline of branded and generic medications, and introduce medicines that will help save and improve lives.

For more information, visit www.purduepharma.com.

References:

Cipriano A, He E, Shet M, Apseloff G, Harris SC. Reversal of fentanyl-induced respiratory depression in healthy subjects by intramuscular nalmefene administered by auto-injector versus intranasal naloxone. J Clin Pharmacol. 2025. https://doi.org/10.1002/jcph.70088
Edinoff AN, Nix CA, Reed TD, et al. Pharmacologic and clinical considerations of nalmefene, a long duration opioid antagonist, in opioid overdose. Psychiatry Int 2021;2(4):365-378.
FDA approval of Zurnai™ (nalmefene injection) auto-injector press release. Purdue Pharma L.P. Accessed August 5, 2025. FDA Approves Zurnai™ (nalmefene injection) Auto-Injector for the Emergency Treatment of Known or Suspected Opioid Overdose Induced by Natural or Synthetic Opioids in Adults and Pediatric Patients 12 Years and Older - Purdue Pharma
Nalmefene Hydrochloride Injection 2mg/2mL (1mg/1mL) [Full Prescribing Information]. Stamford, CT: Purdue Pharma L.P., 02/08/2022. https://www.accessdata.fda.gov/spl/data/d4bb0797-a4ed-4ed4-9904-604433eea4ff/d4bb0797-a4ed-4ed4-9904-604433eea4ff.xml. Accessed August 5, 2025.
Zurnai [Full Prescribing Information]. Stamford, CT: Purdue Pharma L.P., https://www.zurnai.com/pdf/zurnai_FPI.pdf. Accessed August 18, 2025.
Centers for Disease Control and Prevention. Provisional drug overdose data. CDC https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm. Published August 14,2024. Accessed May 30, 2025.
Volkow ND, Collins FS. The role of science in addressing the opioid crisis. N Engl J Med. Jul 27 2017;377(4):391-394. doi:10.1056/NEJMsr1706626