Digoxin × Spironolactone

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.

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.

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%.