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