Moderate
Digoxin × Spironolactone
Cardiac glycosides (digitalis)×Potassium-sparing diuretics (mineralocorticoid receptor antagonists)
Mechanism
Spironolactone moderately inhibits P-glycoprotein; digoxin levels rise by 20–30%. Spironolactone metabolites also cross-react with immunoassay measurements of digoxin, falsely elevating reported values.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
On spironolactone start, reinterpret target digoxin concentration (rather than 0.5–0.9 ng/mL, aim for the lower boundary). Check potassium and creatinine every 2–4 weeks for the first 3 months. With toxicity signs, reduce digoxin by 25%.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Sources
- Lexicomp: Lexicomp Drug Interactions (2024)– Wolters Kluwer Clinical Drug Information, Inc. Lexi-Interact Online, 2024
- Pharmaceutical Press: Stockley's Drug Interactions, 12th edition (2024)– Preston CL (ed.). Stockley's Drug Interactions. 12th ed. London: Pharmaceutical Press; 2024