What is Digitoxin?
Digitoxin is a cardiac glycoside with identical pharmacodynamic effects to digoxin but with distinct pharmacokinetic properties—it is metabolized in the liver rather than renally excreted, making it particularly useful in patients with renal dysfunction and elderly patients. 1
Mechanism of Action
- Digitoxin inhibits sodium-potassium adenosine triphosphatase (Na-K ATPase), resulting in increased intracellular calcium and enhanced myocardial contractility (positive inotropic effect) 2, 3
- It produces a negative chronotropic effect (lowers heart rate), negative dromotropic effect (impedes stimulus conduction), and positive bathmotropic effect (promotes myocardial excitability) 3
- Beyond its inotropic action, digitoxin attenuates neurohormonal activation by sensitizing cardiac baroreceptors and reducing sympathetic outflow 1
Key Pharmacokinetic Differences from Digoxin
- Digitoxin is highly lipophilic with extensive plasma protein binding and a longer half-life compared to digoxin 3
- Elimination occurs primarily through hepatic metabolism via urine and feces, not renal excretion 1, 3
- Digitoxin does not accumulate in kidney dysfunction, making it advantageous in renal impairment and elderly patients 1
- The more stable pharmacokinetic profile may result in lower incidence of toxic side effects compared to digoxin 3
Clinical Applications
- Digitoxin shares the same indications as digoxin for heart failure management, including symptomatic improvement in patients with reduced ejection fraction 1
- It is indicated for rate control in atrial fibrillation with any degree of symptomatic heart failure 1
- In sinus rhythm, digitoxin is recommended for patients with persisting heart failure symptoms despite ACE inhibitor and diuretic treatment 1
- The European Society of Cardiology notes digitoxin as a suitable alternative to digoxin where available 1
Current Evidence and Limitations
- While digoxin has been extensively studied in placebo-controlled trials (including the landmark DIG trial), comparable large-scale studies for digitoxin have not yet been performed 3
- The ongoing DIGIT-HF trial is investigating digitoxin efficacy and safety as adjunct therapy in patients with advanced chronic heart failure with reduced ejection fraction 1, 4
- Based on its pharmacological stability, digitoxin might be associated with even more advantages than digoxin, though this requires confirmation 3
Contraindications
- Bradycardia, second- and third-degree AV block, sick sinus syndrome, carotid sinus syndrome 1
- Wolff-Parkinson-White syndrome, hypertrophic obstructive cardiomyopathy 1
- Hypokalemia and hypercalcemia 1
Clinical Context
- Despite limited contemporary evidence specific to digitoxin, its theoretical advantages in renal dysfunction make it a rational alternative to digoxin in appropriate clinical scenarios 1, 3
- The American College of Cardiology/American Heart Association guidelines note there is little reason to prescribe cardiac glycosides other than digoxin for heart failure management, primarily due to lack of placebo-controlled trial data 1
- However, the European Heart Journal guidelines explicitly recognize digitoxin as one of the most frequently used cardiac glycosides alongside digoxin 1