Digoxin Interactions

Licorice (Glycyrrhiza glabra) contains glycyrrhizin, which inhibits renal 11-beta-hydroxysteroid dehydrogenase type 2 and causes potassium loss through mineralocorticoid-like activity. The resulting hypokalemia sharply increases digoxin's binding to cardiac Na/K-ATPase, raising the risk of life-threatening digoxin toxicity and arrhythmia.

St. John's wort induces intestinal P-glycoprotein, increasing efflux of digoxin and reducing its absorption. Controlled studies show digoxin AUC falls roughly 25% and peak concentrations around 30-36% after two weeks of St. John's wort, potentially producing therapeutic failure in rate control or heart failure management.

Glycyrrhizin in licorice inhibits 11-beta-hydroxysteroid dehydrogenase type 2, mimicking aldosterone excess and causing sodium retention and potassium wasting. The resulting hypokalemia sensitizes the myocardium to digoxin and can trigger toxicity (arrhythmias, heart block) even at therapeutic serum digoxin levels.

Hawthorn (Crataegus) has digoxin-like positive inotropic activity, may modulate P-glycoprotein efflux, and can interfere with serum digoxin immunoassays. Concurrent use raises the risk of additive cardiac effects and erroneous digoxin level readings even though formal pharmacokinetic studies show little change in digoxin AUC.

Dairy products contribute calcium that, when combined with intravenous calcium or high oral loads, can potentiate digoxin's effects on the heart and increase the risk of arrhythmias. Dietary fiber and milk proteins may also modestly reduce digoxin absorption from oral capsules and tablets.

Alcohol can precipitate atrial fibrillation and other arrhythmias that overlap with digoxin's narrow therapeutic window; concurrent diuretic-induced hypokalemia and hypomagnesemia, common in this population, sharply increase the risk of digoxin toxicity. Alcohol may also alter digoxin absorption and worsen heart failure that the drug is meant to treat.