What are the potential interactions between Aldactone (spironolactone) and Digoxin?

Aldactone and Digoxin Interaction

Spironolactone does not alter the pharmacokinetics or clearance of digoxin, but it interferes with certain digoxin immunoassays, causing falsely elevated or lowered serum digoxin measurements depending on the assay used. 1

Key Clinical Points

No True Pharmacokinetic Interaction

• Spironolactone does not inhibit the disposition or clearance of digoxin, contrary to earlier beliefs that were confounded by assay interference rather than true drug interaction. 1

• The combination of spironolactone and digoxin can be safely used together without dose adjustment of digoxin based on pharmacokinetic concerns. 1

Laboratory Assay Interference (Critical Pitfall)

• Spironolactone and its metabolites (canrenone and potassium canrenoate) interfere with radioimmunoassays for digoxin, causing falsely elevated or lowered apparent digoxin concentrations depending on which assay is used. 2, 3, 4, 5

• The fluorescence polarization immunoassay (FPIA) typically shows falsely elevated digoxin levels in the presence of spironolactone. 3, 4, 5

• The microparticle enzyme immunoassay (MEIA) may show falsely lowered digoxin levels when spironolactone is present. 3

• Use an assay that does not interact with spironolactone when monitoring digoxin levels in patients taking both medications—chemiluminescent assays (CLIA) and Tina-quant assays are free from this interference. 2, 3, 4, 5

Practical Management Algorithm

When Prescribing Both Medications

1. Continue both medications without digoxin dose adjustment based solely on the drug combination, as there is no true pharmacokinetic interaction. 1

2. Verify which digoxin assay your laboratory uses before interpreting any digoxin level. 2, 3

3. Request a chemiluminescent or Tina-quant digoxin assay if available, as these are not affected by spironolactone interference. 3, 4, 5

4. Alternatively, measure free digoxin concentration in the ultrafiltrate, which eliminates interference since spironolactone and its metabolites are strongly protein-bound while digoxin is only 25% protein-bound. 3

Monitoring Considerations

• Target digoxin levels of 0.5-1.0 ng/mL regardless of spironolactone use, as higher levels are associated with increased mortality. 1

• Monitor for hyperkalemia when using both medications together, especially in patients also taking ACE inhibitors or ARBs, as this is the primary safety concern with spironolactone (not the digoxin interaction). 1, 2

• Check serum potassium at 1,4,8, and 12 weeks, then at 6,9, and 12 months, then every 6 months. 1, 6

• If potassium rises to 5.5-6.0 mEq/L, reduce spironolactone dose to 25 mg every other day. 1, 6

Common Pitfalls to Avoid

• Do not reduce digoxin dose based on an elevated digoxin level if the patient is on spironolactone and your laboratory uses FPIA—the elevation may be artifactual. 2, 3

• Do not increase digoxin dose if levels appear low on MEIA in a patient taking spironolactone—this may also be artifactual. 3

• Do not confuse assay interference with true digoxin toxicity—clinical signs of toxicity (arrhythmias, GI symptoms, visual changes) should guide management, not just the laboratory value. 1, 7

• The primary risk of combining these medications is hyperkalemia, not digoxin toxicity, particularly when ACE inhibitors or ARBs are also prescribed. 1, 2