indication

For the treatment and management of congestive cardiac insufficiency, arrhythmias and heart failure.

pharmacology

Digitoxin is a cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting (From Martindale, The Extra Pharmacopoeia, 30th ed, p665). Unlike digoxin (which is eliminated from the body via the kidneys), it is eliminated via the liver, so could be used in patients with poor or erratic kidney function. However, it is now rarely used in current UK medical practice. While there have been several controlled trials which have shown digoxin to be effective in a proportion of patients treated for heart failure, there is not the same strong evidence base for digitoxin, although it is presumed to be similarly effective.

mechanism of action

Digitoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digitoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.

toxicity

Digitoxin exhibits similar toxic effects to the more-commonly used digoxin, namely: anorexia, nausea, vomiting, diarrhoea, confusion, visual disturbances, and cardiac arrhythmias.

biotransformation

Hepatic.

drug interactions

Bendroflumethiazide: Possible electrolyte variations and arrhythmias

Bumetanide: Possible electrolyte variations and arrhythmias

Chlorthalidone: Possible electrolyte variations and arrhythmias

Ethacrynic acid: Possible electrolyte variations and arrhythmias

Furosemide: Possible electrolyte variations and arrhythmias

Hydrochlorothiazide: Possible electrolyte variations and arrhythmias

Indapamide: Possible electrolyte variations and arrhythmias

Metolazone: Possible electrolyte variations and arrhythmias

Quinidine: Quinine/quinidine increases the effect of digoxin

Quinine: Quinine/quinidine increases the effect of digoxin

Telithromycin: Telithromycin may reduce clearance of Digitoxin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Digitoxin if Telithromycin is initiated, discontinued or dose changed.

Verapamil: Verapamil may increase the serum concentration of Digitoxin by decreasing its metabolism and clearance. Monitor for changes in the therapeutic/adverse effects of Digitoxin if Verpamail is initiated, discontinued or dose changed.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of digitoxin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of digitoxin if voriconazole is initiated, discontinued or dose changed.