Moderate
Established
Description
Diltiazem significantly increases digoxin plasma levels through P-gp inhibition and may additionally slow AV nodal conduction, exacerbating bradycardia or heart block.
Mechanism
Diltiazem inhibits P-glycoprotein–mediated renal and biliary excretion of digoxin; it also has intrinsic negative chronotropic and dromotropic effects on the AV node, adding to digoxin's vagotonic actions.
Clinical Significance
Digoxin AUC increases by ~20–30%; symptomatic bradycardia, AV block, and digoxin toxicity have been reported.
Management
Monitor heart rate and digoxin levels; reduce digoxin dose by ~25% when initiating diltiazem; avoid combination in patients with pre-existing conduction disease.