Drug in focus: naloxone

11 September, 2025

What is Naloxone?

Naloxone is a life-saving medication used to rapidly reverse the effects of an opioid overdose. It is an opioid antagonist, which means it works by attaching to the same receptors in the brain as opioids (such as heroin, morphine, fentanyl, and codeine), but instead of activating them, it blocks them. This action displaces the opioids from the receptors reversing the life-threatening central nervous system and respiratory depression that can lead to death.

Naloxone is an emergency treatment. Its effects are temporary, typically lasting for 30 to 90 minutes. Because many opioids can remain in a person’s system for a longer period, there is a risk of the overdose effects returning after the naloxone wears off. For this reason, it is crucial to call emergency services (999) immediately after administering naloxone, even if the person’s condition appears to have improved.

Naloxone formulations available in the UK

In the UK, naloxone is available in two main formulations for use in the community:

Intramuscular (IM) Injection: This is a pre-filled syringe that is injected into a large muscle, such as the thigh or upper arm. The most common brand name for this formulation in the UK is Prenoxad®. The kit is designed for easy use by anyone and contains multiple doses.
Prenoxad user guide:
https://www.medicines.org.uk/emc/rmm/2141/Document

For videos on how Prenoxad® should be used:
https://www.prenoxadinjection.com/hcp/how-to.html

Intranasal (IN) Spray: This is a pre-packaged, needle-free device that is sprayed directly into one nostril. This formulation is often preferred by family and friends of people who use opioids, as it is easier to use in an emergency situation. The most common brand name in the UK is Nyxoid®, which provides a single dose per device of 1.8mg. Another brand is Accord’s Naloxone Nasal Spray (the Pebble), which contains the lower dose of 1.26mg per spray.

Do not prime these nasal sprays, as the dose will be lost if this happens.

Naloxone use in Substance Misuse in the UK

In the UK, the use of naloxone has been a cornerstone of public health strategies to combat the high rates of opioid-related overdose deaths. The approach is primarily harm reduction, aiming to save lives and provide a window for professional medical help to arrive.

Take-home Naloxone (THN) programmes: This is the key initiative in the UK’s response to opioid overdose. These programmes distribute naloxone kits to people who use opioids, their friends, and family members. This empowers bystanders to administer the life-saving drug, as many overdoses occur when others are present.
Wider access: The legal framework has been amended to allow a wider range of people to supply naloxone without a prescription, including those working in drug treatment services, homeless services, and community pharmacies. Scotland has been a pioneer in this, with a national naloxone program that makes kits widely available.
Routes of administration: Naloxone is available in the UK in both injectable (intramuscular) and intranasal spray forms. The nasal spray, in particular, has made administration simpler for laypeople in an emergency.
Police and prison services: In a further move to increase availability, some police forces in the UK have trained officers to carry and administer intranasal naloxone. Similarly, there are efforts to ensure that people at risk of overdose, particularly upon release from prison, are provided with a take-home naloxone kit.
Training and education: Take-home naloxone programmes are not just about distributing the kits; they also involve training on how to recognise an overdose, administer naloxone, and the crucial step of calling emergency services. This is vital because the effects of naloxone are temporary, and the individual can return to an overdose state after it wears off.

Key takeaways

Know the signs: unconsciousness, slow/shallow breathing, pinpoint pupils, blue lips/fingers.
Time-critical: short-acting (30–90 mins); opioids may last longer → monitor and repeat if needed.
Opioid-specific: ineffective for non-opioids, but safe to give if in doubt.
Anyone can administer: legal for emergency use by trained or untrained staff.
Never delay: naloxone won’t harm someone who is not on opioids but not giving it to someone with an overdose can be fatal.
Manage opioid-induced respiratory depression carefully in palliative care: use low-dose naloxone unless immediately life-threatening, maintaining airway and oxygenation, and closely monitor post-administration due to naloxone’s short half-life.
Formulations: Naloxone saves lives: reverses opioid overdose quickly and safely.
– Prenoxad: IM injection (5 x 0.4ml doses)
– Nyxoid and Pebble: Nasal spray (2 single-use sprays)
– Injection ampoules: 400mcg/ml.
Post-administration: monitor for at least 2 hours; effects can wear off before opioids do.

Naloxone use in palliative care in the UK

The use of naloxone in palliative care is distinctly different from its use in substance misuse. While it’s still about reversing the effects of opioids, the goal is not to achieve full reversal, but to manage and alleviate unwanted side effects while maintaining pain relief.

Targeted use: In palliative care, opioids are used for long-term pain and symptom management. The inappropriate use of naloxone can cause a rapid and distressing reversal of pain relief and precipitate acute withdrawal symptoms. Therefore, naloxone is used cautiously and in low, titrated doses.
Low-dose regimen: The primary use of naloxone in palliative care is to reverse life-threatening opioid-induced respiratory depression without causing an abrupt and complete reversal of analgesia. Low-dose regimens are used, typically with small, repeated intravenous or intramuscular injections until the patient’s breathing improves. See current BNF/PCF9.
Not for drowsiness or delirium: Naloxone is not indicated for opioid-induced drowsiness or delirium that are not immediately life-threatening.
Monitoring is key: After administration, the patient is closely monitored because the short duration of action of naloxone means the depressant effects of the opioid may return, requiring further doses or a continuous intravenous infusion.
Clinical guidelines: UK palliative care guidelines provide specific protocols for naloxone use in this setting, emphasising the importance of slow, titrated administration and careful patient monitoring to balance the need for respiratory support with the need for pain control. Naloxone is an essential part of the resuscitation kit in clinical areas where opioids are used.

Points to consider

Is the respiratory depression immediately life-threatening? If so give the standard naloxone regimen.

Immediately life-threatening respiratory depression

Use traditional doses over 30 seconds, assess over 1 minute,

If no response, move on to the next dose.

Start with Naloxone 400 micrograms IV
800 micrograms IV
800 micrograms IV
2-4mg IV

If no response to 2-4mg consider an alternate diagnosis, including the possibility of ‘wooden chest’ syndrome.

Is the patient on regular opioids?
Is the patient easily rousable or only responding to painful stimuli?
Is the patient on Buprenorphine?

Review the opioid regimen/consider possible cause or the toxicity.
Pupil size is not a reliable indicator of opioid overdose/toxicity in patients on regular opioids.

Most episodes are preceded by a progressive reduction in consciousness.
In general: when the respiratory rate is <8 breaths per min and patient is:
Unresponsive or only responsive to painful stimuli:

Give naloxone at a lower dose unless episode is immediately life-threatening

Alert/easily rousable:

Watchful waiting, consider omitting or reducing next regular dose

Severe but not immediately life-threatening respiratory depression

Initial treatment

Maintain airway
Administer oxygen to maintain SpO2 >95% (88-92% if pre-existing
hypercapnic respiratory failure)
Discontinue opioid (e.g. stop CSCI/CIVI, remove patch)
Obtain IV access
Administer IV Naloxone (if not practical IM or SC).

If Naloxone is indicated:

Dilute a 1ml ampoule of naloxone 400 micrograms to 4ml with 0.9% sodium chloride

Administer 1ml (100 mcg) IV every 2 mins until respirations are satisfactory

Even lower doses may be used

Administer 20 micrograms IV every 2 mins until respirations are satisfactory

(Dilute 1ml of naloxone 400micrograms per ml to 10ml and administer 0.5ml)

Ongoing treatment (after the last dose of Naloxone)
Monitor level of consciousness and respiratory rate:

Every 15 mins for 2 hours,

then hourly for 6 hours after an immediate release opioid,
longer for an M/R opioid or Methadone

As Naloxone has a short half life compared to most opioids repeat bolus doses may be needed.

If more than 3 bolus doses are needed; consider Naloxone IVI for 24hrs or sometimes longer.

Reversal of buprenorphine-induced respiratory depression

Buprenorphine has both high receptor affinity and prolonged receptor binding. Higher Doses of Naloxone are needed.

Discontinue buprenorphine (stop CSCI/CIVI, remove TD patch)
Give Oxygen by mask
Give IV naloxone 2mg stat over 90 seconds
Commence naloxone 4mg/hr by IVI
Continue CIVI until the patient’s condition is satisfactory (probably <90 mins)
Monitor patient frequently for next 24hrs, restart IVI if respiratory depression recurs
If the patient’s condition remains satisfactory restart the buprenorphine at a reduced dose e.g. half the previous dose

(Reference: Palliative Care Formulary).

Possible causes for an opioid overdose in Palliative Care

Excessive dosing – e.g. pain poorly responsive to opioids, prescription/ administration error
Drug interactions – e.g. prescribing clarithromycin with fentanyl
Accumulation of drug due to long half-life – e.g. methadone
Reduced elimination due to renal failure – e.g. morphine

Restart opioid at a lower dose when there has been a sustained respiratory improvement and consider change of opioid.

When death is expected and imminent: a slow respiratory rate is normal and should not be treated with naloxone.

Key takeaways for palliative care

Unless immediately life-threatening, lower doses of naloxone should be given to avoid rapid reversal of the physiological effects for pain control.
Assess patient –watchful waiting/ decreasing or temporarily stopping opioid treatment (removing patch, stopping CSCI) may be all that is needed.
Monitor patient closely even after discontinuation of naloxone.
Buprenorphine needs higher doses of naloxone to reverse respiratory depression.
Doses of Naloxone are usually given IV / CIVI
Naloxone onset of action: IV 1-2 mins, SC/IM 2-5 mins Plasma half life ~1hr