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Naloxone is an opiate antagonist used in the treatment of opiate overdose.

Naloxone overall is a safe medication, and is not known to cause harm when administered in typical doses to opioid-naïve patients (1)

  • is concern about the precipitation of opioid-withdrawal syndrome following its administration in the setting of prior opioid exposure
  • despite the long-standing use of naloxone to reverse the symptoms of opioid overdose or toxicity, appropriate dosing remains controversial, with varying doses recommended over time and by medical specialty

For advice on managing an opioid overdose:

Aim of naloxone treatment

  • primary aim of treatment is to reverse the toxic effects of opioids so that people are no longer at risk of respiratory arrest, airway loss, or other opioid-related complications

  • urgent or emergency use of naloxone should only ever be considered where there is an immediate threat to life or a diagnosis of respiratory depression (2)

  • respiratory depression is diagnosed as:
    • respiratory rate is 8 breaths per minute or less, and
    • person is barely rousable/unconscious and/or
    • person is cynosed
  • severity of the respiratory depression defines the acuteness of the toxicity, subsequent management, and whether naloxone is indicated.

Take into consideration the following factors when prescribing intravenous naloxone (2):

  • half-life of opioid
    • repeated doses of naloxone may be required in people exposed to an overdose of a long-acting opioid, e.g. buprenorphine, due to incomplete recovery of respiratory function following a single dose of naloxone
    • if the duration of action of the opioid is longer than that of naloxone, then consider a continuous intravenous naloxone infusion
  • extent of respiratory depression
    • higher doses of naloxone may be required in people exposed to an overdose of an opioid with a higher opioid receptor affinity, such as morphine and fentanyl, due to a greater extent of respiratory depression.
  • Type of opioid
    • mechanical ventilation may be required, in addition to naloxone, in people exposed to an overdose of a partial opioid antagonist (e.g. buprenorphine) due to incomplete reversal of opioid induced respiratory depression.
  • physical dependence on opioids
    • withdrawal symptoms such as tachycardia may occur within a few minutes of administering naloxone in people who are physically dependent on opioids.
  • risk of adverse effects from naloxone
    • there is a greater risk of sudden adverse effects (e.g. nausea, vomiting, sweating or tachycardia) from opioid reversal with intravenous naloxone use
    • the dose and administration rate of naloxone may increase the risk of adverse effects
    • post-surgery, high doses of naloxone can cause excitement, hypertension, and reversal of the required opioid analgesia
  • Unknown cause of severe respiratory depression
    • naloxone has no reversal effect on people who do not have opioids in their system
    • naloxone treatment should still be considered to reverse severe respiratory depression in people presenting with signs and symptoms of an opioid overdose where the cause is unknown

Current evidence suggests that in the hands of trained medical personnel in an environment replete with additional life-support equipment, favoring the avoidance of withdrawal by utilizing a small initial dose of naloxone is safe (1) - most expeditious route of administration (i.e. IM) may at times be necessary, but in general IV dosing is most reliably efficacious, titratable and predictable

  • however, in the hands of laypeople without adequate training or equipment to provide prolonged respiratory support, the risk of under-dosing naloxone far outweighs the potential risks of precipitating opioid withdrawal (1)
    • in these cases
      • risk of inadequate reversal of opioid toxicity is far greater than the risk posed by over-antagonizing respiratory depression to the point of precipitating opioid withdrawal, as the latter is unpleasant but rarely life-threatening, while untreated opioid overdose is frequently fatal, particularly as the incidence of overdose due to potent synthetic opioids rises

Nasal spray formulations of naloxone, are currently used for the treatment of opioid overdose in the United States (US) (3).


  • Rzasa Lynn R, Galinkin JL. Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf. 2018 Jan;9(1):63-88.
  • NHS Specialist Pharmacy Service (October 2022). Reversing an adult opioid overdose with naloxone in the medical setting
  • Taylor JL, Lasser KE. Intranasal Naloxone for Opioid Overdose. JAMA. 2024;331(3):250–251. doi:10.1001/jama.2023.23248


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