Mechanisms of Amiodarone Toxicity

Today in report, the question was posed about amiodarone toxicity: is it related to strength of a single dose or total cumulative dose? Turns out it’s both! Depending on the toxicity and whether it’s PO or IV amiodarone.

Take Home Points: Mechanisms of Amiodarone Toxicity for IV and PO Dosing

IV Amiodarone

  • Hypotension – up to 26% of pts who receive amiodarone. Attributed to solvents used in IV amio prep.
  • Arrhythmia – seen in 1-3% of pts getting IV amiodarone. Often tosades de pointes or VF. More common if patients have underling electrolyte abnormalities or active ischemia when given amiodarone.
  • Other adverse effects that occur in 1-5% of cases each: bradycardia, asystole, heart failure, nausea, vomiting, abnormal LFTs

PO Amiodarone 

  • Pulmonary toxicity – correlates closely with total cumulative dose more than serum drug levels.
    • Occurs in 5-15% of pts taking >400mg/day, 1-2% taking <400mg/day.
  • Hyper or hypothyroidism – due to direct thyrotoxic effect of amio + the high iodine content of amio. Risk of toxicity relates to pt’s underlying thyroid status and dietary iodine intake.
    • Occurs in 2-25% of pts takine >400 mg/day, 3-4% taking <400 mg/day.
  • Hepatotoxicity – Likely relates to total cumulative dose.
    • Symptomatic heptatitis occurs in <3% of pts.
  • Neurologic dysfunction – tremors, ataxia, neuropathy, sleep disturbance. Related to single dose strength, not cumulative dose. More frequent during loading dosing and higher daily doses.
    • Rate 3-30% overall.

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