Question 11

College Answer

The question asked for a detailed account of the side effects of amiodarone, hence those candidates that just provided a list or outline scored less well. It was expected that candidates provide some detail of the side effect. Answers that scored well prioritised those relevant to ICU clinical practice. Many provided disorganised outlines of the side effects and frequently the cardiovascular side effects were poorly explained. Many candidates omitted the important drug interactions of amiodarone use and few candidates related the side effect profile to the duration of treatment.

Discussion

Short-term adverse effects:

• Bradycardia (5%)
• QT prolongation
• Torsades de pointes (<1%)
• Hypotension with rapid IV administration (due to polysorbate 80)

Long-term adverse effects by system:

• Pulmonary
  • Pulmonary fibrosis (1.6%)
• Dermatological
  • Photosensitivity (25-75%)
  • Blue skin discolouration (<10%)
• Ophthalmic
  • Corneal deposits and cataracts (100%)
  • Optic neuritis (<1%)
• Thyroid
  • Wolff-Chaikoff effect: iodine-induced hypothyroidism (1-23%)
  • Hyperthyroidism can also occur (1-32%)
• Hepatic
  • LFT derangement (15%)
  • Hepatitis and cirrhosis (<3%)
• Neurological
  • Ataxia, tremor, peripheral neuropathy
  • Sleep and memory disturbances
• Urogenital
  • Epididymitis
• Obstetric
  • Penetrates the placenta, causing iodine overload and hypothyroidism of the foetus, causing neurodevelopmental abnormalities
  • Excreted into breast milk

Drug interactions

• By binding to albumin and other protein, amiodarone can displace other highly protein-bound drugs, and increase their free fraction (increasing their effect)
• Inhibitor of P-glycoprotein, an efflux pump involved in the elimination of digoxin:
  • People on combined digoxin/amiodarone therapy will have unexpectedly elevated digoxin levels 
• Acts as an inhibitor for CYP 3A4, which means the following common drugs will have impaired clearance:
  • Warfarin
  • Atorvastatin and simvastatin
  • Flecainide
  • Quinidine
  • Phenytoin
  • Cyclosporin

Hamilton, David, et al. "Amiodarone: a comprehensive guide for clinicians." American Journal of Cardiovascular Drugs (2020): 1-10.

van Erven, Lieselot, and Martin J. Schalij. "Amiodarone: an effective antiarrhythmic drug with unusual side effects." Heart 96.19 (2010): 1593-1600.

Martino, Enio, et al. "The effects of amiodarone on the thyroid." Endocrine reviews 22.2 (2001): 240-254.

Fenster, Paul E., Neal W. White Jr, and Christine D. Hanson. "Pharmacokinetic evaluation of the digoxin-amiodarone interaction." Journal of the American College of Cardiology 5.1 (1985): 108-112.

Holt, David W., et al. "Amiodarone pharmacokinetics." American heart journal 106.4 (1983): 840-847.