Naloxone

Mechanism of action:  Naloxone is an opioid antagonist and reverses the effects of opioids including respiratory depression, sedation and hypotension.

Presentation:  solution for injection

Absorption:

Intravenous:     bioavailability of 100% with very rapid time to peak concentration

Intramuscular:  bioavailability of 36% with a time to peak concentration: 12 minutes with sustained measurable concentrations for up to 4 hours

Intranasal:        poor bioavailability of 4% (prob due to swallowing part of the dose, where oral bioavailability is less than 1%) with a time to peak concentration: 6-9 minutes, and little or no continued effect

Protein binding:  approx. 45% protein bound, primarily to albumin

Metabolism:  Naloxone is hepatically metabolized and undergoes glucuronidation to form naloxone-3-glucuronide.

Elimination:  Renally excreted as metabolites

Half-life:  30-80 mins.  If given intravenously, the patient must be monitored closely due to the risk of re-sedation after 30 mins

 

Suggested dose:

1. Are you concerned that the patient is drowsy because of their opioids?

Consider your diagnosis:

  • Reduced level of consciousness
  • Reduced respiratory rate below 8 breaths / minute
  • Oxygen saturation less than 85% on room air
  • Reason for opioid toxicity - renal function impaired, pyrexia in a patient with a transdermal patch, recent increase in opioids (e.g. 50 – 100% increase in dose over 2 days)   
  • If on supplemental oxygen check if a history of COPD and consider blood gas to check for acidosis due to CO2 retention
  • If on oxygen, no COPD and saturations over 94% drowsiness is most unlikely to be due to opioids

 Give naloxone: Dilute 400microgram (1mL) to 10mls with sodium chloride 0.9%.

  • Give 40 micrograms (1mL) over 30 seconds intravenously (IV).  If no IV access easily available give IM or SC (slower onset action)
  • Repeat every 2 minutes up to a total of 5 times

If no response, reconsider your diagnosis: other reasons for sedation eg CVA, hypoglycaemia, benzodiazepine toxicity etc

 

2. In an emergency situation where you suspect that the patient has taken or been given an opioid overdose. This is most usually associated with drug misuse and dependence.

Consider your diagnosis

  • Reduced level of consciousness
  • Reduced respiratory rate below 8 breaths / minute
  • Evidence of recent opioid administration

Give naloxone:

  • Give 400 micrograms over 30 seconds IV (intravenously)
  • At 1 minute give 800 microgram IV (Total now 1200 microgram)
  • After a further minute give 800 microgram IV (Total now 2000 microgram)
  • If no response give 2mg IV (Total now 4mg)
  • If no IV access easily available give IM (slower onset action)
  • Give 400 micrograms at 3 minute intervals  IM until effect noted

Further prescribing information (side effects, contraindications, interactions):

BNF-Naloxone

References

Dowling J, Isbister GK, Kirkpatrick CM et al. Population pharmacokinetics of intravenous, intramuscular, and intranasal naloxone in human volunteers.  Ther Drug Monit 2008; 30(4):490-6. doi: 10.1097/FTD.0b013e3181816214.

https://www.rxlist.com/narcan-drug.htm#clinpharm

Hanes SD, Franklin M, Kuhl DA et al. Prolonged opioid antagonism with naloxone in chronic renal failure. Pharmacotherapy 1999; 19(7):897-901