digoxin and verapamil

Verapamil inhibits P-glycoprotein-mediated renal tubular secretion of digoxin, increasing its plasma concentration. Additionally, both drugs have additive negative chronotropic and dromotropic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block.

Elevated digoxin levels can cause gastrointestinal symptoms (nausea, vomiting), visual disturbances, and cardiac arrhythmias. The additive electrophysiological effects increase the risk of symptomatic bradycardia, AV block, and rarely asystole. Patients with pre-existing conduction disease, renal impairment, or the elderly are at higher risk.

Monitor digoxin plasma concentrations before and after starting verapamil, and adjust the digoxin dose downwards (often by 25-50%) as guided by levels. Monitor ECG and heart rate. Consider using a different calcium channel blocker (e.g., amlodipine) if appropriate, and avoid combination in patients with significant conduction abnormalities or heart block.

Well-established interaction, supported by multiple clinical studies and case reports. Both pharmacokinetic (P-glycoprotein inhibition) and pharmacodynamic mechanisms are well documented.