What is the recommended use and dosage of digitoxin (digitalis glycoside) for treating heart failure and arrhythmias?

Digitoxin for Heart Failure and Arrhythmias

Digitoxin is not recommended as a first-line treatment for heart failure or arrhythmias, with digoxin being the preferred cardiac glycoside with a Class IIa recommendation according to current guidelines. 1, 2

Indications and Clinical Use

Cardiac glycosides like digitoxin and digoxin may be considered for:

• Patients with symptomatic heart failure with reduced ejection fraction (HFrEF <40%) who remain symptomatic despite guideline-directed medical therapy (GDMT) 2
• Rate control in atrial fibrillation, particularly when:
  • Resting heart rate >80 bpm
  • Exercise heart rate >110-120 bpm
  • Used before or in addition to beta-blockers 2

Digoxin (not digitoxin) reduces heart failure hospitalizations but does not reduce mortality, making it a second-line agent after diuretics, ACE inhibitors, and beta-blockers for patients in sinus rhythm 2, 3.

Dosage and Administration

While digitoxin-specific dosing is limited in current guidelines, digoxin dosing (which can be used as a reference) should be:

• Standard adult dose: 0.25 mg/day for patients with normal renal function 2, 4
• Elderly patients (>70 years): 0.125-0.0625 mg/day 2
• Renal impairment adjustment:
  • Mild impairment (eGFR 45-59 mL/min): 0.125 mg daily
  • Moderate impairment (eGFR 30-44 mL/min): 0.125 mg daily or every other day
  • Severe impairment (eGFR <30 mL/min): 0.0625-0.125 mg every other day 2

For rapid digitalization (rarely needed), a loading dose can be administered in divided portions:

• Initial dose: 0.5-0.75 mg
• Additional doses of 0.125-0.375 mg at 6-8 hour intervals with careful clinical assessment 4

Therapeutic Monitoring

• Therapeutic range: 0.6-1.2 ng/mL 2
• Toxicity commonly occurs at levels >2.0 ng/mL 1, 2, 4
• Routine measurement of serum levels is not necessary in most patients 2, 3
• Serum sampling should be done just before the next scheduled dose or at least 6-8 hours after the last dose 4

Safety Considerations and Contraindications

Digitoxin/digoxin is contraindicated in:

• Second or third-degree heart block without a pacemaker
• Pre-excitation syndromes
• Previous evidence of digitalis intolerance 2

Use with caution in:

• Post-MI patients, particularly with ongoing ischemia 1
• Patients with electrolyte disorders (hypokalemia, hypomagnesemia, hypercalcemia) 2, 4
• Hypothyroidism 2, 4
• Elderly patients 1, 2

Drug Interactions

Dose reduction (30-50%) is required when co-administered with:

• Amiodarone
• Verapamil
• Diltiazem
• Clarithromycin
• Erythromycin
• Itraconazole
• Quinidine 2, 4, 3

Toxicity Management

Signs of toxicity include:

• Cardiac arrhythmias
• Gastrointestinal symptoms (anorexia, nausea, vomiting)
• Neurological complaints (visual disturbances, disorientation, confusion) 1, 2

For toxicity management:

• Hold the medication
• Correct electrolyte abnormalities
• Consider digoxin-specific antibody fragments for severe toxicity (serum levels >4 ng/mL with serious arrhythmias) 2

Clinical Efficacy

Digoxin (and by extension, digitoxin) improves:

• Symptoms
• Quality of life
• Exercise tolerance
• Reduces heart failure hospitalizations 3, 5

However, it does not reduce overall mortality 2, 3, 5.

Important Considerations

• The American College of Cardiology/American Heart Association has downgraded cardiac glycosides from Class I to Class IIa recommendation due to narrow risk/benefit ratio 1
• Digitoxin appears in fewer current guidelines than digoxin, with limited comparative data showing similar efficacy but potentially better achievement of therapeutic levels 6
• Monitoring for toxicity is essential, especially in patients with risk factors like renal impairment or electrolyte disorders 1, 2, 4