Digoxin-Amiodarone Interaction Management
When starting amiodarone in a patient taking digoxin, immediately reduce the digoxin dose by 50% and monitor digoxin levels closely, as digoxin levels predictably double due to amiodarone's inhibition of renal tubular secretion and P-glycoprotein transport. 1
Mechanism of Interaction
- Amiodarone inhibits digoxin secretion from renal tubules, causing a predictable doubling of digoxin plasma concentrations 1
- P-glycoprotein membrane transporter inhibition by amiodarone further reduces digoxin clearance 1, 2
- This interaction is one of the most clinically important drug interactions with amiodarone, alongside warfarin 1
Critical Management Algorithm
At Initiation of Amiodarone:
- Reduce digoxin dose by 50% immediately when starting amiodarone 1
- Check baseline digoxin level before starting amiodarone 1
- Monitor digoxin levels closely during the loading phase and every 6 months thereafter 1
Monitoring Schedule:
- Check digoxin levels at baseline, during amiodarone loading, and every 6 months during maintenance therapy 1
- If digoxin toxicity is suspected, immediately check digoxin level 1
- Monitor heart rate closely, especially during the first week of amiodarone treatment 1
Signs of Digoxin Toxicity to Monitor
- Bradycardia or heart block (amiodarone itself can cause bradycardia in 4.9% of patients when given IV) 1
- Gastrointestinal symptoms (nausea, vomiting, anorexia)
- Visual disturbances (yellow-green halos, blurred vision)
- Cardiac arrhythmias (ventricular ectopy, AV block)
Critical Pitfall to Avoid
The interaction persists for months after amiodarone discontinuation due to amiodarone's extremely long half-life (averaging 58 days) and extensive tissue accumulation 3. Even after stopping amiodarone, digoxin levels may remain elevated for 3+ months, requiring continued dose adjustment and monitoring 3.
Additional Cardiovascular Considerations
- Additive bradycardic effects can occur from the combination, particularly in patients with underlying sinus node dysfunction 1
- Both drugs prolong AV nodal conduction, increasing risk of heart block 1
- Amiodarone is contraindicated in patients with second- or third-degree heart block without a pacemaker 1
Practical Dosing Strategy
- Standard digoxin dose of 0.25 mg/day should be reduced to 0.125 mg/day when amiodarone is initiated 4
- Recheck digoxin level 1-2 weeks after dose adjustment to ensure therapeutic range (0.5-2.0 ng/mL, though lower targets of 0.5-0.9 ng/mL are often preferred)
- Further dose reductions may be necessary based on clinical response and measured levels 1, 5