Opioid overdose

Last reviewed: 25 Aug 2023
Last updated: 04 Aug 2023
04 Aug 2023

US FDA approves nalmefene nasal spray, a fast-onset and long-duration opioid overdose reversal agent

The US Food and Drug Administration (FDA) has approved prescription nalmefene, an opioid receptor antagonist, for the emergency treatment of known or suspected opioid overdose.

If administered quickly, nalmefene can reverse or prevent the effects of opioid overdose, including respiratory depression, sedation and hypotension. Nalmefene has a longer duration of action than naloxone (the only other FDA-approved opioid overdose reversal drug) at fully reversing doses and has no opioid agonist activity.

Opioid overdose remains a major public health issue globally, and particularly in the US. Data from the CDC’s National Center for Health Statistics indicate that reported overdose deaths involving opioids in the US increased from 72,081 in the 12-month period ending February 2021 to 79,644 in the 12 months ending February 2023.

The approval of nalmefene nasal spray comes a couple of months after the FDA approved the first naloxone nasal spray for nonprescription use. Together, these approvals represent another vital step in ongoing efforts to prevent opioid-driven deaths.

See Management: emerging

Original source of update



History and exam

Key diagnostic factors

  • history of opioid use disorder and dependence
  • miosis
  • bradypnea
  • altered mental status
  • dramatic response to naloxone
More key diagnostic factors

Other diagnostic factors

  • fresh needle marks
  • drug paraphernalia nearby
  • decreased gastrointestinal motility
  • old track marks on arms and legs
  • pulmonary rales
  • frothy pink sputum
  • seizures
  • dysrhythmias
Other diagnostic factors

Risk factors

  • opioid use disorder and dependence
  • recent abstinence in chronic users
  • chronic pain
More risk factors

Diagnostic investigations

1st investigations to order

  • therapeutic trial of naloxone
  • Electrocardiogram (ECG)
More 1st investigations to order

Investigations to consider

  • chest x-ray
  • abdominal x-ray
  • abdominal CT scan
  • opioid urine screen
  • gas chromatography/ mass spectrometry
More investigations to consider

Treatment algorithm


patients with signs of opioid overdose or toxicity: in cardiac arrest

patients with signs of opioid overdose or toxicity: not in cardiac arrest



Ruben Thanacoody, MD, FRCP

Consultant Physician and Clinical Toxicologist

Director, National Poisons Information Service (Newcastle)




RT declares that he has no competing interests.


Dr Ruben Thanacoody would like to gratefully acknowledge Dr Dean Olsen, a previous contributor to this topic.


DO declares that he has no competing interests.

Peer reviewers

William Winter, MD


Gynecologic Oncologist

Northwest Cancer Specialists

Rose Quarter Cancer Center




WW declares that he has no competing interests.

Anne-Maree Kelley, MD, MClinEd, FACEM


Joseph Epstein Centre for Emergency Medicine Research

Western Health Sunshine Hospital

St Albans



AMK has received grant funding for research into intranasal delivery of naloxone in heroin overdose.

Andrew Stolbach, MD

Assistant Professor

Johns Hopkins University




AS declares that he has no competing interests.

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