Drug interactions that increase the risk of digoxin toxicity
| Medication | Mechanism of interaction | Comments |
|---|---|---|
| Amiodarone, quinidine, dronedarone, nondihydropyridine calcium channel blockers (diltiazem and verapamil), propafenone, flecainide, clarithromycin, cyclosporine, itraconazole | Inhibition of P-glycoprotein, a drug efflux pump that mediates secretion of digoxin in the kidney, liver, and gut | Digoxin dose may have to be decreased to half when starting any of these medications Check digoxin levels 1 week after starting any P-glycoprotein inhibitor |
| Macrolides (azithromycin, clarithromycin, erythromycin) and tetracycline | Decreased initial degradation of digoxin by gut microflora, leading to increased drug absorption | Monitor levels closely when co-administering digoxin with these antibiotics |
| Diuretics, amphotericin B | Decreased glomerular filtration rate and hypokalemia can increase digoxin toxicity | Monitor potassium levels to avoid hypokalemia |
| Nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, cyclosporine | Decreased glomerular filtration rate and acute kidney injury | Telmisartan increases digoxin concentration by about 50% |
| Beta-blockers, nondihydropyridine calcium channel blockers | Slowing of atrioventricular conduction can lead to bradycardia compounding on digoxin’s vagotonic effects | Increased risk of bradycardia; carvedilol can increase digoxin concentration |
| Amiodarone, sotalol, quinidine, procainamide, dofetilide, ibutilide, quinolones, macrolides, azole antifungals, tricyclic antidepressants, antipsychotics, methadone | QT-prolonging agents increase risk of life-threatening arrhythmias as digoxin increases early afterdepolarizations, which can lead to R-on-T phenomenon and torsade de pointes | Monitor QT closely when adding any of these medications |
Based on information from references 17 and 18.