What is Nalmefene (Zurnai)?

Nalmefene, available under the brand name Zurnai, is an opioid receptor antagonist that is used for the emergency treatment of a known or suspected opioid overdose in adult patients and children 12 years of age and older.

Zurnai (nalmefene) autoinjector is a rescue medication for an acute overdose of natural or synthetic opioids. Nalmefene can reverse the life-threatening effects of an opioid overdose, including drug-induced respiratory depression (slowed or stopped breathing), sedation (excessive sleepiness/drowsiness), and hypotension (low blood pressure).

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Nalmefene Dosage Forms

Nalmefene is currently available in the U.S. under the brand names Zurnai (available 2025) and Opvee.

Zurnai (nalmefene hydrochloride injection) - 1.5 milligrams (mg)/0.5 milliliters (mL) auto-injector for subcutaneous or intramuscular administration (available 2025). Zurnai is a single-dose, pre-filled autoinjector that delivers 1.5 mg of nalmefene subcutaneously (under the skin) or intramuscularly (into the muscle).
Opvee (nalmefene hydrochloride nasal spray) - 2.7 mg of nalmefene per spray. Each nasal spray device contains one dose, delivering 2.7 mg of nalmefene into one nostril. Each package includes two nasal spray devices to provide two doses to be repeated after 2 minutes if needed.

Other brand names:

Revex: Nalmefene hydrochloride injection solution for intravenous, subcutaneous, and intramuscular administration — discontinued in 2008 due to low sales.
Selincro: Nalmefene oral tablets — not available in the U.S.

Is Nalmefene Available in the U.S.?

Yes, nalmefene is available in the U.S. The U.S. Food and Drug Administration (FDA) approved the first nalmefene hydrochloride nasal spray (brand name: Opvee) in May 2023 for use in health care and community settings. This medication is available by prescription to treat acute opioid overdose.

Zurnai is the newest nalmefene product approved by the FDA in August 2024 and will be available in 2025. Zurnai is a single-dose, pre-filled autoinjector that delivers 1.5 mg of nalmefene subcutaneously (under the skin) or intramuscularly (into muscle).

Why Was Nalmefene Discontinued?

The injectable form of nalmefene, sold under the brand name Revex, was discontinued in 2008 for commercial reasons. The injection of nalmefene needed to be given via intravenously (IV, into the vein), intramuscular (IM, into the muscle), or subcutaneous (SC, under the skin) routes. Doctors did not find a role for the nalmefene injection due to it being challenging to use and its duration of action.

However, a new nalmefene injectable product is due to come on the market in 2025 under the brand name Zurnai. This will be a nalmefene injection for intramuscular and subcutaneous administration and will be available in the form of an auto-injector that will deliver 1.5 mg/0.5 mL of nalmefene. Being a single-dose, pre-filled autoinjector, Zurnai is designed for convenient and accurate administration.

Medical Uses: What is Nalmefene an Antidote For?

Opioid Overdose in People with Opioid Dependence

Nalmefene acts on the opioid system in the body by binding to brain opioid receptors. It works by affecting the three main opioid receptors (mu-opioid, delta-opioid, and kappa opioid) in a way that reverses the effects of opioids. Nalmefene also blocks these opioid receptors in various brain signaling pathways, including the mesolimbic pathway, a part of the brain involved in mediating addictive behaviors to opioids and other drugs of abuse.

High doses of opioid drugs produce respiratory depression (slowed or stopped breathing) and other serious opioid drug effects, including low blood pressure and extreme sedation. By readily crossing the blood-brain barrier and binding to opioid receptors, nalmefene occupies these brain receptors. In other words, it prevents opioid drugs from binding to these brain opioid receptors, thereby reversing the life-threatening effects of synthetic and natural opioids.

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Alcohol Use Disorders

Nalmefene reduces alcohol consumption in people with alcohol use disorders. However, the opiate receptor antagonist nalmefene is not FDA-approved in the United States for use in patients with alcohol dependence or addiction. Experts have concluded that nalmefene treatment shows no benefit over naltrexone, which is an established medication to treat alcohol dependence.

The European Medicines Agency has approved nalmefene to help people reduce their alcohol consumption by reducing cravings for alcohol. It is approved for the treatment of alcohol dependence in adults who consume more than 60 grams (men) or 40 grams (women) of alcohol per day (a can of beer contains 16 grams of alcohol, and a small glass of wine contains about 12 g of alcohol).

Nalmefene vs Naltrexone vs Naloxone

What Is The Difference Between Nalmefene and Naltrexone?

Nalmefene and naltrexone are structurally similar opioid receptor antagonists. Similar to naltrexone, nalmefene is an antagonist at the μ- and δ-opioid receptors (mu-opioid and delta-opioid receptors), but it additionally has a unique mechanism of action as a κ-opioid (kappa-opioid) partial agonist.

By binding to opioid receptors in the body, both nalmefene and naltrexone prevent the endorphin response that is responsible for the pleasurable effects of alcohol. These drugs, therefore, reduce alcohol cravings and help people with alcohol dependence reduce alcohol consumption.

Nalmefene is not yet approved for use by alcohol-dependent patients in the US, although it has been approved for this indication in Australia and some European countries.

What Is The Difference Between Naloxone and Nalmefene?

Naloxone is the standard antidote for an opioid overdose. Nalmefene is a newer opioid antidote and has some unique characteristics compared to naloxone, including:

A higher affinity for opioid receptors
A longer half-life — nalmefene lasts over 5 times longer than naloxone; specifically, nalmefene’s half-life is 11 hours vs naloxone’s 60-90 minutes
A longer duration of action than naloxone and the potential to reverse opioid intoxication for up to 8 hours, reducing the need for repeated dosing and continuous monitoring

However, evidence suggests that nalmefene may result in more prolonged and severe opioid withdrawal compared to naloxone, which could be harmful.

Nalmefene vs Naloxone Therapeutic Efficacy: Clinical Trial Results

A study that was sponsored by Indivior, the manufacturer of Opvee nasal spray, compared the effects of intranasal naloxone hydrochloride (4 mg) and intranasal nalmefene (2.7 mg) in reversing respiratory depression induced by remifentanil (an opioid) in healthy adult male subjects. The results showed that nalmefene-treated subjects had a greater increase in minute respiration and that nalmefene had a more rapid onset of action than naloxone.

Nonetheless, experts say there is not enough comparative data on the safety and effectiveness of naloxone vs nalmefene. Additionally, scientists are not yet sure if nalmefene is beneficial in an opioid overdose outside of clinical studies. On the other hand, there are decades of experience in the use of naloxone as an antidote for known or suspected opioid overdose, including synthetic opioids such as fentanyl and fentanyl analogs.

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Guidelines for Nalmefene Use

Nalmefene (Opvee Nasal Spray) is for intranasal use only. It is to be used for the emergency treatment of a known or suspected overdose of natural or synthetic opioids in adults and children 12 years and older who have symptoms of central nervous system (CNS) depression, such as slowed or stopped breathing, excessive sleepiness, or low blood pressure.

Nalmefene should be used immediately when an opioid overdose is known or suspected. The single-use device is ready to use. Each use of the Opvee nasal spray delivers a single dose of nalmefene, and the device cannot be reused.

A person experiencing an opioid overdose is unable to use the rescue medication themselves. People around them should, therefore, know how to use nalmefene nasal spray.

Caregivers should follow these instructions to administer nalmefene intranasally:

Administer the medication as soon as possible. Prolonged CNS and respiratory depression can result in permanent brain damage or death.
Seek emergency medical care after administering the first dose of nalmefene. This medication is not a substitute for emergency medical care.
Stay with the person and monitor them continuously until emergency personnel arrive.
Additional nalmefene may be necessary and should be administered with a new nasal spray in the opposite nostril. A dose can be repeated every 2 to 5 minutes if there is no response or relapse to respiratory depression after the first dose.

If nalmefene is used in someone not experiencing an opioid overdose and there are no opioid drugs in their system, the drug has no effect or side effects.

How to Use Nalmefene Nasal Spray (Opvee)?

Place the person in a supine position (lay them flat on their back).
Insert the nozzle of the device into the person’s nostril.
Support the back of their neck and tilt their head back.
There is no need to test or prime the device before using it.
Press the plunger firmly to deliver the nalmefene dose.
Remove the nasal spray device from the person’s nose after use.

If the person wakes up, starts responding to voice or touch, and starts breathing normally, place them in the recovery position (on one side). Call emergency medical services immediately after giving the first dose of nalmefene nasal spray.

Nalmefene Dosing

A single dose of nalmefene nasal spray (Opvee) delivers 2.7 mg of the medicine. Keep in mind that each nasal spray contains only one dose. However, Opvee is packaged to include two nasal spray devices to provide two doses since one dose may not be enough to treat an overdose. Repeat dosing may be necessary depending on the type, amount, and method of use of the opioid drug on which the person has overdosed.

You need to use a new nasal spray to deliver each additional dose. If the patient does not respond, you can give them additional nalmefene nasal spray with a dose every 2 to 5 minutes until emergency medical services arrive.

Side Effects of Nalmefene

The most common adverse effects of nalmefene nasal spray include:

Nasal discomfort
Nasal congestion
Throat irritation
Rhinalgia (pain in the nose)
Headache
Dizziness
Flushing
Nausea
Vomiting
Fatigue
Anxiety
Decreased appetite
Erythema (skin redness)
Hyperhidrosis (excessive sweating)

In addition, the use of nalmefene hydrochloride in opioid-dependent patients can result in physical withdrawal symptoms such as:

Body aches
Fast heartbeat
Fever
Diarrhea
Abdominal cramps
Runny nose and sneezing
Goosebumps
Yawning
Sweating
Nausea or vomiting
Restlessness, irritability, nervousness
Shivering or trembling
Weakness or fatigue
Increased blood pressure

Warnings

Recurrent Respiratory and CNS Depression

In the community setting, an opioid overdose may be complicated by the use of multiple or unknown drugs, including long-acting opioids. This can result in a recurrence of respiratory depression following an initial response to nalmefene nasal spray. For this reason, it is important to stay with the patient until emergency assistance arrives and to give them additional nalmefene, if needed.

Limited Effectiveness Against Partial Agonists or Mixed Agonists/Antagonists

The ability of nalmefene to reverse an opioid overdose with partial agonists or mixed agonists/antagonists such as buprenorphine and pentazocine may be incomplete, and repeat doses may be required.

Severe Opioid Withdrawal Symptoms

The use of nalmefene in opioid-dependent patients can produce acute withdrawal symptoms. Sudden opioid overdose reversal can result in tachycardia (fast heartbeat), hypotension (low blood pressure), hypertension (high blood pressure), seizures (convulsions), cardiac arrhythmias, pulmonary edema (fluid in the lungs), cardiac arrest, coma, brain damage, and death. Patients with pre-existing cardiovascular disorders are at a higher risk of these adverse events. It is, therefore, important to get emergency medical assistance as soon as possible after the first dose of nalmefene.

Risk of Opioid Overdose from Attempts to Overcome the Blockade

As mentioned, the use of nalmefene nasal spray can cause withdrawal effects in opioid-dependent patients. Such individuals are at risk of an opioid overdose if they attempt to overcome the withdrawal effects caused by opioid antagonists such as nalmefene by consuming high or repeated doses of opioids.

Safety and Efficacy

Nalmefene for Opioid Overdose

Nalmefene is a potent opioid antagonist that has recently been reintroduced in the United States for the treatment of known or suspected opioid overdose. The injection formulation of nalmefene was withdrawn in 2008 and reintroduced in 2022. In 2023, the FDA approved Opvee, a new nasal spray formulation of nalmefene, under the Abbreviated New Drug Application since only the route of administration was different.

As a result of this abbreviated approval process, the intranasal formulation of nalmefene has not been studied for effectiveness in patients experiencing an opioid overdose. In other words, intranasal nalmefene is untested in the clinical environment for synthetic opioid overdoses. It may potentially cause harm due to prolonged opioid withdrawal.

The American College of Medical Toxicology and the American Academy of Clinical Toxicology have recommended that until additional clinical studies are done to evaluate the safety and effectiveness of nalmefene, it should not replace naloxone as the main antidote in patients receiving opioid antagonists.

Nalmefene for Alcohol Use Disorder

Animal studies have shown that alcohol intake is suppressed to a greater extent with nalmefene compared to naltrexone. In humans, randomized, placebo-controlled trials have found that people with alcohol dependence in the nalmefene group taking it as needed had significantly reduced heavy drinking days and improvement in liver enzymes, indicating a possible reversal of liver injury caused by an alcohol use disorder.

Meta-analysis of double-blind, placebo-controlled, randomized controlled trials have shown nalmefene use has a significant benefit in reducing heavy drinking days and overall alcohol consumption. There are no head-to-head trials comparing the benefits of nalmefene vs. naltrexone. Keep in mind that nalmefene is not approved for use as the treatment of alcohol use disorder in the U.S. at this time.

Check out our blog, “Alcohol Withdrawal Symptoms: A Complete Guide for Recovery.”

Drug Interactions

Give your doctor and pharmacist a complete list of your prescription drugs, over-the-counter medications, dietary supplements, and herbal products to avoid drug interactions between nalmefene and your other medications.

Research and Emerging Applications: Recent Studies and Clinical Trials

Oral nalmefene (Selincro) 18 mg tablet is being evaluated in a clinical trial that has enrolled alcohol-dependent patients with alcoholic cirrhosis who have a high drinking risk level. Nalmefene could be a useful treatment to reduce heavy drinking in patients with alcoholic cirrhosis because of its potential to improve liver function. There is no comparison drug available, however, because other medications for patients with alcohol dependence, such as acamprosate, disulfiram, and naltrexone, require abstinence from alcohol prior to starting treatment.

Find out: How Does Acamprosate Reduce Alcohol Cravings?

Naloxone

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