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AMIODARONE

CLASS

Antiarrhythmic

PRESENTATION

Clear, colourless solution.

Formulations

  • 3ml vial; 150mg, 50mg/ml

INDICATIONS & DOSING

Cardiac arrest (shockable pathway; ventricular fibrillation or tachycardia)

  • Adult; 300mg IV/IO
  • Paediatric; 5mg/kg IV/IO
  • Given as an IV push 

Tachyarrhythmias; supraventricular/nodal tachyarrhythmias including atrial fibrillation and flutter, ventricular tachycardia, Wolff-Parkinson-White syndrome

  • Adult; loading dose 300mg IV, infusion 900mg over 24 hours
  • Paediatric; loading dose 5mg/kg IV, infusion 15mg/kg over 24 hours
  • Loading dose given as a slow IV push over 1-2 minutes in the critical patient
  • Loading dose given over a minimum of 20 minutes in the non-critical patient
  • Loading dose may be repeated up to a maximum of 15mg/kg within 24 hours for breakthrough arrhythmias
  • Infusion rate is adjusted according to clinical response

PRACTICALITIES

Administration

  • Give neat in cardiac arrest
  • Dilute loading dose into 10-20ml 5% dextrose in the critical patient
  • Dilute loading dose into 250ml 5% dextrose in the non-critical patient
  • Preferentially administered via central venous line (dilute solution is safe for administration through a peripheral vein)

Incompatibilities

  • Sodium chloride
  • Heparin
  • Aminophylline
  • Plasticisers (PVC-containing fluid bags, administration lines) 

Practice tips

  • Continuous ECG and BP monitoring required during intravenous administration
  • If present, correct hypokalemia, hypomagnesemia or hypocalcemia to counter the QT prolongation effect of amiodarone as well as optimise success of its antiarrhythmic action

PHARMACOKINETICS

Onset

  • IV/IO; 1-30 minutes, most respond within 1 hour

Duration of action

  • IV loading dose; 1-3 hours
  • After establishing steady-state the duration of action is varied and largely unknown due to dual contribution to action by both primary drug and metabolites, and variable patient-dependent elimination 

Metabolism

Metabolised in the liver to desmethylamiodarone which possess anti-arrhythmic and anti-CYP450 activity 

Elimination

Excreted by the lacrimal gland, skin and biliary tract. Long elimination half-life; 15-140 days.

MECHANISM

Predominantly Vaughan Williams class III (but also class I, II and IV) anti-arrhythmic activity. 

Blockade of K+ channels slows repolarisation, increasing the duration of the action potential and refractory period. Antagonism of alpha and beta adrenoceptors.

DESIRED CLINICAL EFFECTS

Cardiovascular

  • Antiarrhythmicity, predominantly nodal

OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES

Cardiovascular (acute)

  • Hypotension with rapid IV administration (mild negative inotropy and vasodilatation, potentiated by general anaesthesia)
  • Bradycardia (sinus rate slowed by ~15%), high grade conduction block (slowed AV node conduction, potentiated by general anaesthesia – may not be responsive to anticholinergics/chronotropes and require temporary pacing)
  • QT prolongation 

Cardiovascular (chronic)

  • Congestive cardiac failure 

Respiratory (chronic)

  • Pneumonitis, fibrosis, pleuritis
  • Acute pulmonary toxicity (potentially related to high FiO2) 

Neurological (chronic)

  • Peripheral neuropathy
  • Myopathy 

Gastrointestinal (chronic)

  • Cirrhosis, hepatitis, jaundice
  • Metallic taste
  • GI upset 

Endocrine (chronic)

  • Hyper/hypothyroidism 

Other (chronic)

  • Corneal micro-deposits
  • Photosensitivity
  • Slate-grey skin colour

CONSIDERATIONS

Precautions

  • High grade conduction block
  • Sinoatrial node dysfunction with bradycardia
  • Iodine hypersensitivity
  • Administration under general anaesthesia 

Obstetric

ADEC category C; cardiac, thyroid, neurodevelopment effects 

Drug interactions

  • Highly protein bind (>95%), displaces highly protein bound drugs, increasing their free fraction and effect (warfarin, phenytoin, digoxin)
  • Additive action with other drugs that cause AV conduction delay, may lead to conduction block (e.g. non-dihydropiridine calcium channel blockers, beta-blockers, digoxin)
  • Additive action with other drugs that cause QT prolongation, may lead to torsades de pointes (e.g. SSRIs, TCAs, MAO-inhibitors, lithium, ondansetron, methadone, sotalol, droperidol
  • Cytochrome inhibition, increases concentrations of drugs metabolised by certain CYP450 isoenzymes (CYP1A2; lidocaine, theophylline, CYP2C9; warfarin, CYP2D6; metoprolol, flecainide, CYP3A4; cyclosporine A, simvastatin), concentration increased/decreased by inhibitors/inducers of CYP3A4 (e.g. rifampicin, loratadine, cimetidine)

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)
  • Clinical experience of authors

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