Nalmefene

Mechanism-of-action class: Opioid Antagonists.

• Nalmefene hydrochloride injection is indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. Nalmefene hydrochloride injection is indicated in the management of known or suspected opioid overdose.

• Nalmefene hydrochloride injection is contraindicated in patients with a known hypersensitivity to the product.contraindicated

Important Information - Dosage Form Nalmefene hydrochloride injection is supplied in a 2 mL vial as a 1 mg/mL concentration suitable for the management of overdose. Proper steps should be taken to prevent use of the incorrect concentration. General Principles Nalmefene hydrochloride injection should be titrated to reverse the undesired effects of opioids. Once adequate reversal has been established, additional administration is not required and may actually be harmful due to unwanted reversal of analgesia or precipitated withdrawal. Duration of Action The duration of action of nalmefene hydrochloride injection is as long as most opioid analgesics. The apparent duration of action of nalmefene hydrochloride injection will vary, however, depending on the half-life and plasma concentration of the narcotic being reversed, the presence or absence of other drugs affecting the brain or muscles of respiration, and the dose of nalmefene hydrochloride injection administered. Partially reversing doses of nalmefene hydrochloride injection (1 mcg/kg) lose their effect as the drug is redistributed through the body, and the effects of these low doses may not last more than 30 to 60 minutes in the presence of persistent opioid effects. Fully reversing doses (1 mg/70 kg) have been shown to last many hours in both experimental and clinical studies, but may complicate the management of patients who are in pain, at high cardiovascular risk, or who are physically dependent on opioids.

Use of Nalmefene Hydrochloride Injection in Emergencies Nalmefene hydrochloride injection, like all drugs in this class, is not the primary treatment for ventilatory failure. In most emergency settings, treatment with nalmefene hydrochloride injection should follow, not precede, the establishment of a patent airway, ventilatory assistance, administration of oxygen, and establishment of circulatory access. Risk of Recurrent Respiratory Depression Accidental overdose with long acting opioids [such as methadone and levo -alpha-acetylmethadol (LAAM)] may result in prolonged respiratory depression. Respiratory depression in both the postoperative and overdose setting may be complex and involve the effects of anesthetic agents, neuromuscular blockers, and other drugs. While nalmefene hydrochloride injection has a longer duration of action than naloxone in fully reversing doses, the physician should be aware that a recurrence of respiratory depression is possible, even after an apparently adequate initial response to nalmefene hydrochloride injection treatment. Patients treated with nalmefene hydrochloride injection should be observed until, in the opinion of the physician, there is no reasonable risk of recurrent respiratory depression.

Adverse event information was obtained following administration of nalmefene hydrochloride injection to 152 normal volunteers and in controlled clinical trials to 1127 patients for the treatment of opioid overdose or for postoperative opioid reversal. Nalmefene was well tolerated and showed no serious toxicity during experimental administration to healthy individuals, even when given at 15 times the highest recommended dose. In a small number of subjects, at doses exceeding the recommended nalmefene hydrochloride injection dose, nalmefene produced symptoms suggestive of reversal of endogenous opioids, such as have been reported for other narcotic antagonist drugs. These symptoms (nausea, chills, myalgia, dysphoria, abdominal cramps, and joint pain) were usually transient and occurred at very low frequency. Such symptoms of precipitated opioid withdrawal at the recommended clinical doses were seen in both postoperative and overdose patients who were later found to have had histories of covert opioid use. Symptoms of precipitated withdrawal were similar to those seen with other opioid antagonists, were transient following the lower doses used in the postoperative setting, and more prolonged following the administration of the larger doses used in the treatment of overdose. Tachycardia and nausea following the use of nalmefene in the postoperative setting were reported at the same frequencies as for naloxone at equivalent doses. The risk of both these adverse events was low at doses giving partial opioid reversal and increased with increases in dose.

Use in Pregnancy Reproduction studies have been performed in rats (up to 1200 mg/m 2 /day) and rabbits (up to 2400 mg/m 2 /day) by oral administration of nalmefene and in rabbits by intravenous administration up to 96 mg/m 2 /day (114 times the human dose). There was no evidence of impaired fertility or harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Metabolism

Nalmefene exhibited dose proportional pharmacokinetics following intravenous administration of 0.5 mg to 2 mg. Pharmacokinetic parameters for nalmefene after a 1 mg intravenous administration in adult male volunteers are listed in Table 1.

Intravenous doses of up to 24 mg of nalmefene, administered to healthy volunteers in the absence of opioid agonists, produced no serious adverse reactions, severe signs or symptoms, or clinically significant laboratory abnormalities. As with all opioid antagonists, use in patients physically dependent on opioids can result in precipitated withdrawal reactions that may result in symptoms that require medical attention. Treatment of such cases should be symptomatic and supportive. Administration of large amounts of opioids to patients receiving opioid antagonists in an attempt to overcome a full blockade has resulted in adverse respiratory and circulatory reactions.

• Feb 8, 2022ANDAANDA212955Knoa Pharma
• May 22, 2023NDANDA217470Indivior
• Nov 15, 2023ANDAANDA216007Chengdu Shuode
• Aug 7, 2024NDANDA218590Knoa Pharma

1. 1Therapy Non-responder513%
2. 2Bradycardia410%
3. 3Bradypnoea410%
4. 4Coma410%
5. 5Electrocardiogram Qt Prolonged410%
6. 6Hypothermia410%
7. 7Intentional Overdose410%
8. 8Miosis410%
9. 9Pneumonia Aspiration410%
10. 10Diabetic Ketoacidosis37.7%
11. 11Drug Withdrawal Syndrome37.7%
12. 12Nausea37.7%
13. 13Pulmonary Oedema37.7%
14. 14Aggression25.1%
15. 15Agitation25.1%

The 10 most recently updated of 39 ClinicalTrials.gov registrations naming Nalmefene as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Pharmacokinetic (PK) Evaluation of Nalmefene Formulations
  Completed · Phase 1 · Interventional · 13 enrolled · Knoa Pharma LLC
  NCT07543276updated 2026-06-05
• Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation
  Completed · Phase 1 · Interventional · 13 enrolled · National Institute on Alcohol Abuse and Alcoholism (NIAAA)
  NCT02639273updated 2026-06-05
• Nalmefene Implant in Healthy Subjects
  Recruiting · Phase 1 · Interventional · 24 enrolled · ReacX Pharmaceuticals, Inc.
  NCT07325279updated 2026-04-06
• Effect of Nalmefene on the Quality of Resuscitation in Patients Under General Anesthesia
  Completed · Phase 4 · Interventional · 542 enrolled · RenJi Hospital
  NCT04713358updated 2026-02-25
• TH104 for the Treatment of Pruritus in Primary Biliary Cholangitis
  Not yet recruiting · Phase 2 · Interventional · 40 enrolled · Tharimmune Inc
  NCT06733519updated 2025-09-09
• Pharmacodynamic Evaluation of Intranasal Nalmefene
  Completed · Phase 1 · Interventional · 84 enrolled · Opiant Pharmaceuticals Inc
  NCT04828005updated 2025-07-14
• Pharmacodynamic Evaluation of Intramuscular Nalmefene Autoinjector 1.5 mg Compared to Intranasal Narcan 4 mg
  Completed · Phase 1 · Interventional · 24 enrolled · Purdue Pharma LP
  NCT06719986updated 2025-07-03
• An Evaluation of The Absolute Bioavailability of TH104
  Completed · Phase 1 · Interventional · 20 enrolled · Tharimmune Inc
  NCT06198686updated 2025-04-08
• Post-Marketing Surveillance Study of Nalmefene Hydrochloride Hydrate in Patients with Alcohol Dependence
  Completed · Observational · 533 enrolled · Otsuka Pharmaceutical Co., Ltd.
  NCT04107051updated 2025-03-21
• NAlmefene Versus Placebo in Addition to Treatment as Usual on Craving in Behavioural Addictions
  Recruiting · Phase 3 · Interventional · 266 enrolled · Nantes University Hospital
  NCT05540288updated 2025-02-12

Frequently asked questions

How does Nalmefene work?

Mechanism-of-action class: Opioid Antagonists.

What is Nalmefene used for?

According to FDA labeling, Nalmefene carries indications including: Nalmefene hydrochloride injection is indicated for the complete or partial reversal of opioid drug effects, including respiratory depression, induced by either natural or synthetic opioids. Nalmefene hydrochloride injection is indicated in the management of known or suspected opioid overdose.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Nalmefene?

Nalmefene is classified as Drugs used in alcohol dependence, Opioid Antagonist, Opioid Antagonists, Central Nervous System Stimulation, Increased Blood Pressure, Increased Medullary Respiratory Drive.

What are the brand names for Nalmefene?

Nalmefene is marketed under brand names including Opvee, Zurnai.

What are the contraindications for Nalmefene?

Nalmefene labeling lists contraindications including: Nalmefene hydrochloride injection is contraindicated in patients with a known hypersensitivity to the product.. Always consult the full prescribing information and a clinician.