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NALOXONE

CLASS

Opioid antagonist

PRESENTATION

Clear, colourless solution.

Formulations

  • 1ml vial, 400mcg, 400mcg/ml

INDICATIONS & DOSING

Acute opioid overdose
Opioid-related side-effects; respiratory depression, pruritus, nausea, Sphincter of Oddi spasm

  • Adult; 40mcg-2mg IV/IM/SC/IN
  • Paediatric; 5-10mcg/kg IV/IM/SC/IN 

Prevention of opioid-related constipation (mixed opioid-naloxone formulations)

  • Adult; 5/2.5mg, 10/5mg, 20/10mg, 40/20mg PO

PRACTICALITIES

Administration

  • Boluses; 400mcg naloxone in 0.9% N/saline up to 10ml; 40mcg/ml, titrate in 40mcg boluses, titrate to clinical effect at 2-3 minute intervals, commence low dose to avoid reversal of opioid analgesic effect unless clinically warranted
  • Infusion; 2mg naloxone in 100ml N/saline; 20mcg/ml, commence infusion at 5-10mcg/kg/hr or 2/3 of previous hour dose requirement, titrate to response

Incompatibilities

  • Avoid coadministration especially with preparations containing bisulfite or metabisulfite (all inotropes/vasopressors except ephedrine, milrinone, vasopressin), alkaline pH, or large anions

Practice tips

  • The duration of action of naloxone may be shorter than the duration of the opioid being reversed (particularly long-acting agents – morphine, hydromorphone, higher dose fentanyl, SR oral opioids); ~2 hours observation for recrudescence of opioid effects is warranted, supplementary dosing or an infusion may be required
  • Reversal of the effects of buprenorphine may be incomplete or require higher dosing due to its high receptor affinity
  • Naloxone has been investigated for its use in septic shock and clonidine overdose, though its clinical role is not established

PHARMACOKINETICS

Onset

  • IV/IN; 2 minutes
  • IM/SC; 3-5 minutes

Duration of action

  • IV/IN; 30-90 minutes
  • IM/SC; 60-180 minutes

Metabolism
Majority hepatic metabolism by gluronidation

Elimination
Majority renal elimination

MECHANISM

A substituted derivative of oxymorphone, reverses opioid receptor agonism at MOP, KOP, DOP and SOP receptors. Highest affinity for MOP receptors.

When orally administered in combination with oxycodone SR (Targin), naloxone undergoes significant first-pass metabolism and therefore systemic effects are avoided. However its local effects on intestinal opioid receptors reduce opioid-related constipation.

DESIRED CLINICAL EFFECTS

Respiratory

  • Reversal of opioid-related respiratory depression 

Cardiovascular

  • Reversal of opioid-related haemodynamic instability 

Neurological

  • Reversal of opioid-related sedation
  • Reversal of opioid-related pruritus 

Gastrointestinal

  • Reversal of opioid-related constipation

OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES

Airway

  • Reversal of opioid-related airway reflex ablation 

Cardiovascular

  • Malignant cardiac arrhythmias with irritable myocardial states
  • Hypertension at doses (high-dose)
  • Pulmonary oedema (high-dose) 

Neurological

  • Ant-analgesia in some opioid-naive patients (high-dose) 

Other

  • Precipitates acute opioid withdrawal in opioid tolerant patients; tachycardia/arrhythmias, hypertension, pulmonary oedema, fever, anxiety/irritability, seizures, shivering, diaphoresis, nausea/vomiting, abdominal pain, diarrhoea

CONSIDERATIONS

Precautions

  • Acute pain; reversal of analgesia
  • Opioid tolerance; precipitation of acute opioid withdrawal
  • Unknown safety profile in patients with hepatic or renal impairment
  • Oral combination formulations (Targin) demonstrate a higher bioavailability of naloxone in the setting of hepatic impairment; avoid due to potential for systemic effects, dose reduce if changing from a mixed to a pure opioid formulation

Obstetric 
ADEC category B1; may precipitate neonatal withdrawal in the setting of an opioid-dependent gestation 

Drug interactions

  • Opioid antagonists

REFERENCES

Drug information has been compiled from multiple sources including

  • Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
  • Micromedex (IBM)
  • BJA Education (Oxford Academic)
  • Pharmacology for Anaesthesia and Intensive Care (Cambridge)
  • Australian Prescriber (NPS MedicineWise)

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