Amiodarone is Contraindicated as a Treatment for Digoxin Toxicity
Amiodarone should never be used to treat digoxin toxicity—it will worsen the toxicity by doubling digoxin levels and exacerbating life-threatening arrhythmias and conduction disturbances. The appropriate treatment for severe digoxin toxicity with ventricular arrhythmias is digoxin-specific Fab antibody fragments, not amiodarone 1.
Why Amiodarone Worsens Digoxin Toxicity
Pharmacokinetic Interaction
- Amiodarone predictably doubles serum digoxin concentrations through two mechanisms: inhibition of digoxin secretion from renal tubules and inhibition of the P-glycoprotein membrane transporter system 2, 3.
- This interaction occurs rapidly—digoxin levels increase by 70% within one day of starting amiodarone 3.
- The metabolite N-desethylamiodarone further reduces digoxin clearance, with a 3% decrease in clearance for every 100 ng/mL increase in N-desethylamiodarone concentration 4.
Additive Cardiac Toxicity
- Both drugs cause bradycardia and heart block, creating dangerous additive effects 5.
- Amiodarone causes bradycardia and heart block in 1-3% of patients on oral therapy and 4.9% with IV administration 5.
- The combination should be used with extreme caution even in therapeutic situations, as it can precipitate severe bradycardia requiring temporary pacemakers 6.
Correct Management of Digoxin Toxicity
For Ventricular Arrhythmias
- Digoxin-specific Fab antibody fragments are the treatment of choice for severe digoxin poisoning with ventricular arrhythmias or persistent hyperkalemia 1.
- If Fab fragments are unavailable and ventricular tachycardia/fibrillation is refractory to lignocaine and phenytoin, amiodarone may be used as a last resort for the arrhythmia itself, followed immediately by Fab fragments to bind the digoxin 1.
For Bradycardia and Heart Block
- Temporary pacing is indicated for severe bradycardia or heart block 7.
- Atropine may be used for symptomatic bradycardia.
Supportive Measures
- Correct electrolyte abnormalities, particularly hypokalemia and hypomagnesemia, which worsen digoxin toxicity 7.
- Monitor renal function closely, as impaired clearance (CLcr ≤30 mL/min) significantly increases toxicity risk 4.
Critical Clinical Pitfall
The single case report describing amiodarone use in digoxin overdose 1 does not support amiodarone as a treatment for digoxin toxicity. In that case, amiodarone was used to treat refractory ventricular arrhythmias as an emergency measure when standard antiarrhythmics failed, not to treat the underlying digoxin toxicity. The patient still required Fab antibody fragments to definitively manage the poisoning 1.
Additional Considerations
Thyroid Function
- Amiodarone-induced hypothyroidism can precipitate or worsen digoxin intoxication by reducing digoxin clearance 6.
- This represents another mechanism by which amiodarone can contribute to digoxin toxicity in chronic therapy.
When Drugs Are Used Together Therapeutically
- If amiodarone must be added to a patient already on digoxin (for rhythm control, not toxicity), reduce digoxin dose by 50% immediately 2, 3.
- Monitor digoxin levels closely and observe for clinical signs of toxicity: bradycardia, heart block, nausea, vomiting, visual changes, and cardiac arrhythmias 2.