Amiodarone

Original article by Khaleel Loonat | Last updated on 21/1/2016
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Mechanism of action

  • Blocks K+ channels, therefore prolonging the refractory period
  • Also effective at blocking Na+, having a high affinity for inactivated channels
  • Anti-adrenergic effects by non-competitively blocking α and β receptors
  • Also has weak Ca2+ blocking effect
  • Slows down the sinus rate and AV conduction, and slightly prolongs the QT interval
  • It can also cause peripheral vasodilation

 

Indication and dose

Amiodarone is an anti-arrhythmic drug. Used particularly when other drugs have been ineffective or contra-indicated. It is most commonly used in atrial fibrillation and atrial flutter, but is also indicated in:

  • Paroxysmal Supraventricular
  • Nodal + ventricular tachycardia
  • AF + Flutter
  • Ventricular fibrillation
  • Tachyarrhythmia’s associated with Wolf-Parkinson-White syndrome

Should only be initiated in a hospital or under specialist supervision

 

Oral

  • 200mg TDS for a week
  • Then reduced 200mg BD for another week
  • Followed by a maintenance dose, usually 200mg OD or the minimum dose required to control arrhythmia.

IV Infusion

  • Initially 5mg/kg,  given over 20-120 min with ECG monitoring
  • Subsequent infusions given if necessary according to the patient’s response. MAX DOSE 1.2mg DAILY

Ventricular Fibrillation or pulseless ventricular tachycardia refractory to defibrillation:

Initially by IV injection

  • Initially 300mg
  • Dose to be considered after adrenaline has been administered
  • Dose given from a pre-filled syringe/ diluted in 20ml glucose 5%
  • Then by IV injection 150mg if required
  • Followed by IV infusion, 900mg/24hr

 

Contraindications (CI)

  • Severe conduction disturbances (unless pacemaker fitted)
  • Sinus node disease (Unless pacemaker fitted)
  • Iodine sensitivity
  • Sino atrial heart block (except in cardiac arrest)
  • Sinus bradycardia (except in cardiac arrest)
  • Thyroid dysfunction

 

Specific CI: with IV use

  • Avoid bolus injection in cardiomyopathy
  • Avoid bolus injection in congestive heart failure
  • Avoid in circulatory collapse
  • Avoid in severe arterial hypotension
  • Avoid in severe respiratory failure

 

Side effects

  • Corneal micro deposits: Many patients develop corneal micro deposits
  • Thyroid function: Amiodarone contains Iodine, therefore can cause disorders of thyroid function
  • Hepatotoxicity
  • Pulmonary toxicity
  • Peripheral neuropathy

Pregnancy: possible risk of neonatal goitre. Only use if there is no other alternative
Breast feeding: Avoid, due to drug present in breast milk. Theoretical risk of neonatal hypothyroidism.

Monitoring tests

  • TFT: Before treatment and every 6 months
  • LFT: Before treatment and every 6 months
  • Serum K+ before treatment
  • Chest X-ray before treatment
  • Patients with high risk of bradycardia should be monitored continuously for 48hr in a clinical setting
  • Patients taking amiodarone (Due to other drugs being contra-indicated or not tolerated) with daclatasvir and sofobuvir should be monitored, especially in first week of treatment
  • Patients who stopped amiodarone in the last few months and need to start sofosbuvir and daclatasvir  should be monitored
  • IV amiodarone: use ECG and resuscitation facilities must be available. Monitor liver transaminases  closely

 

Interaction

Amiodarone has a long t1/2    therefore, there is a potential for drug interactions to occur for several weeks or months after treatment has been discontinued.
The list of interactions here are POTENTIALLY SERIOUS in the BNF which is indicated with a black dot and further details of these interactions can be found in the BNF or Stockleys.
Furthermore, there are other interactions which are not potentially serious, nevertheless they still should be monitored and clinical judgement should be used by using pharmacodynamics and pharmacokinetic knowledge.

  • Anti-arrhythmic: Disopyramide or Dronedarone, Flecainide
  • Anti-bacterials: Erythromycin, Levofloxacin, Moxifloxacin, Delamanid, Telithromycin
  • Anticoagulants: Coumarins, Phenindone, Dabigatran
  • Anti-depressants: Citalopram, Escitalopram, Tricyclics
  • Anti-epileptics: Fosphenytoin, Phenytoin
  • Anti-Histamine: Mizolastine
  • Antimalarial: Artemether with Lumefantrine, Artenimol with Piperaquine, chloroquine, hydroxylcholorquine, Mefloquine, Quinine
  • Antimuscarinic: Tolterodine
  • Antipsychotics: Should check BNF with all antipsychotics
  • Antivirals: Should check BNF with all antivirals
  • Atomoxetine
  • Beta-Blockers: especially Sotalol
  • Ca2+ Blockers: Diltiazem, Verapamil
  • Cardiac Glycosdie: Digoxin
  • Cobicistat
  • Colchicine
  • Cytotoxics: Bosutinib, Ibrutinib, Vandetanib, Arsenic Trioxide
  • Fingolimod
  • Ivabradine
  • Simvastatin
  • Lithium
  • Pentamidine

 

 Additional Notes

  • Amiodarone is a phototoxic drug. Therefore, patients will need to be counselled about possible phototoxic reactions. They should be advised to shield their skin from the sun during treatment and also for several months once treatment has been discontinued (wide spectrum sunscreen blocker should be used, which protect against long wave UV and normal visible light)
  • Patients (or carers) taking amiodarone alongside sofosbuvir and daclatasvir should be advised on how to recognise the signs and symptoms of bradycardia and heart block. And should seek medical attention ASAP.
  • Symptoms include: SOB, syncope, light-headedness, palpitations, chest pain and unusual tiredness.