A patient safety alert highlighted the risks of giving inappropriate doses of naloxone. We guide on using appropriate intravenous doses in the medical setting.

Dealing with an opioid overdose

An opioid overdose is a medical emergency.

For advice on managing an opioid overdose:

NICE provides general advice on assessing people who have a suspected overdose.

Safety risk from an inappropriate naloxone regimen

The 2014 Patient Safety Alert highlights the risk of rapid opioid reversal with administering naloxone when it is not indicated or used in larger than recommended doses.

Giving too much naloxone can cause acute opioid withdrawal symptoms and a return of pain. Other potentially life-threatening effects such as cardiac arrhythmias, pulmonary oedema and cardiac arrest can occur.

People at risk

People at a higher risk of adverse events from inappropriate naloxone regimens include chronic opioid users, palliative care, and opioid misusers (especially if physically dependent).

Aim of naloxone treatment

The 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.

Respiratory depression is diagnosed as:

  • respiratory rate is 8 breaths per minute or less, and
  • person is barely rousable/unconscious and/or
  • person is cyanosed

The severity of the respiratory depression defines the acuteness of the toxicity, subsequent management, and whether naloxone is indicated.

Selecting a naloxone regimen

Refer to your local opioid overdose policy for advice on naloxone regimens and administration in case they differ to the BNF and/or manufacturers advice.

Prescribe a high-dose or low-dose intravenous naloxone regimen.

High-dose intravenous naloxone regimens

High-dose intravenous naloxone regimens aim to produce an instant reversal of respiratory depression.

Clinical scenarios for use include:

  • risk of death from acute opioid overdose
  • caution in people with opioid dependence since abrupt cessation of the opioid effect can cause acute opioid withdrawal symptoms which may be life-threatening, e.g. tachycardia

Low-dose intravenous naloxone regimens

Low-dose intravenous naloxone regimens aim to produce a controlled reversal of respiratory depression in less life- threatening situations. It is useful when a tailored reversal of opioid adverse effects is required.

Clinical scenarios for use include:

  • long-term opioid analgesia where respiratory depression requires reversal alongside pain management and the avoidance of opioid withdrawal symptoms, e.g. palliative care, prescribed opioids (for acute or chronic pain), post-operative care

Prescribing considerations

Intravenous naloxone is the preferred route.

Take into consideration the following factors when prescribing intravenous naloxone.

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.

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.

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.

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.

Unknown cause of 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. 

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

How to administer naloxone

Several preparations and strengths of naloxone are available. Check the specific product and strength carefully.

Naloxone can be given by rapid intravenous injection or as a continuous intravenous infusion using an infusion pump.

After the initial intravenous naloxone dose, naloxone doses may need to be repeated at 2 to 3 minute intervals until satisfactory respiration is obtained.

Using continuous infusion

People who have taken long-acting  (e.g. buprenorphine), potent opioids (e.g. oxycodone) or particularly large overdoses may require an infusion of naloxone to maintain spontaneous normal breathing due to its short half-life of 1 to 1.5 hours.

Other routes of administration


Intramuscular naloxone is an alternative if intravenous access is not possible, or in a non-medical setting.

Intramuscular naloxone is only available as a 400micrograms dose so doses are given in subsequent resuscitation cycles (every 2 to 3 minutes). It has a slower onset of action than intravenous naloxone and a prolonged duration of effect.


Intranasal naloxone is intended for immediate administration in an emergency in both non-medical and healthcare settings. It was developed for administration by non-medical persons.

Intranasal naloxone is available as  Nyxoid 18mg naloxone per spray and is as effective as intramuscular naloxone in the pre-hospital management of opioid overdose.


Once breathing is restored:

  • monitor blood gases
  • oxygen saturation
  • respiratory rate

Refer to the Poisons Information Database (Toxbase, registration required) for specific advice.

All patients should be monitored for recurrence of signs and symptoms of opioid toxicity, such as relapse in respiratory symptoms, for at least 4 hours from the last dose of naloxone or discontinuation of the naloxone infusion.

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