What is the recommended dosage and usage of Digoxin (digitalis glycoside) for treating heart conditions?

Digoxin Dosing and Usage for Heart Conditions

Standard Maintenance Dosing

For most adults under 70 years with normal renal function, initiate digoxin at 0.25 mg once daily; for patients over 70 years or with impaired renal function, start at 0.125 mg daily; and for those with marked renal impairment, begin at 0.0625 mg daily. 1, 2

Dosing by Patient Characteristics:

• Patients <70 years with normal renal function: 0.25 mg daily 2
• Patients ≥70 years OR impaired renal function: 0.125 mg daily 1, 2
• Marked renal impairment (CrCl <30 mL/min): 0.0625 mg daily 1, 2
• Every-other-day dosing: Appropriate for elderly patients with significant renal impairment 3

Target Therapeutic Range

Maintain serum digoxin concentration between 0.5-0.9 ng/mL, as concentrations above 1.0 ng/mL provide no additional benefit and may increase mortality risk. 4, 3

• The older therapeutic range of 0.6-1.2 ng/mL has been replaced by the lower target of 0.5-0.9 ng/mL based on mortality data 4, 3
• Check digoxin levels early during chronic therapy in patients with normal renal function 4
• In renal impairment, steady state takes longer to achieve (up to 3 weeks), requiring more careful monitoring 1, 4

Clinical Indications

Heart Failure with Reduced Ejection Fraction (HFrEF):

Digoxin should be considered for patients with LVEF <40% and NYHA class II-IV symptoms who remain symptomatic despite optimal therapy with ACE inhibitors/ARBs, beta-blockers, and diuretics. 1, 3

• Mortality effect: Neutral—does not reduce or increase mortality 1, 5
• Hospitalization benefit: Reduces heart failure hospitalizations by 28% (risk ratio 0.72; 95% CI 0.66-0.79) 6
• Symptom improvement: Improves quality of life and exercise tolerance 5, 7
• Most beneficial in patients with severe heart failure, cardiomegaly, and third heart sound 7

Atrial Fibrillation:

For atrial fibrillation with rapid ventricular rate (>80 bpm at rest, >110-120 bpm with exercise), digoxin may be used for rate control, particularly in patients with concurrent heart failure or sedentary lifestyle. 1, 3

• Combination therapy preferred: Digoxin plus beta-blocker is more effective than digoxin alone, especially during exercise 3
• Monotherapy limitations: Digoxin alone is inadequate for rate control during high adrenergic states 6, 7
• Maximum daily dose: Do not exceed 0.25 mg daily for atrial fibrillation; if inadequate control, add beta-blocker rather than increasing digoxin 3

Loading Dose Protocol (Rarely Indicated)

Loading doses are NOT recommended for stable outpatients with chronic heart failure—start directly with maintenance dosing. 8, 5

When Loading IS Appropriate:

• Hemodynamically unstable supraventricular tachycardia unresponsive to other measures 8
• Atrial fibrillation with rapid ventricular rate causing acute decompensation 8

IV Loading Protocol (if urgently needed):

• Initial dose: 0.25-0.5 mg IV bolus 8
• Additional doses: 0.25 mg at 6-8 hour intervals 8
• Maximum total: 1.0 mg over 24 hours 8
• Check digoxin level 6-24 hours after final loading dose 8

Oral Loading Protocol:

• Total loading dose for 70 kg patient: 750-1250 mcg (0.75-1.25 mg) 2
• Administer roughly half as first dose, then additional fractions at 6-8 hour intervals 2

Absolute Contraindications

Do not use digoxin in patients with: 1, 3

• Second- or third-degree AV block without permanent pacemaker 1, 8
• Pre-excitation syndromes (Wolff-Parkinson-White with AF) 1, 3
• Sick sinus syndrome without pacemaker 1
• Hypertrophic obstructive cardiomyopathy 1
• Previous digoxin intolerance 1

Critical Drug Interactions Requiring Dose Reduction

When adding medications that increase digoxin levels, reduce digoxin dose and monitor levels closely: 1, 3

• Amiodarone: Reduce digoxin by 30-50% 3, 9
  • For patients with CrCl >30 mL/min on amiodarone: 0.0625 mg daily 3, 9
  • For patients with CrCl ≤30 mL/min and N-desethylamiodarone >600 ng/mL: 0.03125 mg daily 9
• Dronedarone: Reduce digoxin by at least 50% 3
• Verapamil, diltiazem, quinidine: Reduce dose and monitor 1, 3
• Macrolide antibiotics (clarithromycin, erythromycin): Monitor closely 3

Signs of Digoxin Toxicity

Suspect toxicity if any of the following occur, even with therapeutic levels: 1, 4, 5

Cardiac manifestations:

• Ventricular arrhythmias (especially with hypokalemia) 1, 4
• Sinoatrial and AV block 1
• Atrial arrhythmias 1

Non-cardiac manifestations:

• Confusion, disorientation 1, 3
• Nausea, anorexia, vomiting 1, 4, 3
• Visual disturbances (yellow-green color vision changes) 1, 4

Risk factors for toxicity:

• Hypokalemia (maintain K+ >4.0 mEq/L) 8, 5
• Hypomagnesemia 3, 5
• Hypothyroidism 3, 5
• Renal impairment 1

Monitoring Requirements

Essential monitoring parameters:

• Serum potassium and magnesium: Check before initiating and regularly during therapy 3, 8
• Renal function: Monitor creatinine clearance to adjust dosing 1, 2
• Digoxin levels: Check early during therapy, then only when toxicity suspected or drug interactions occur 4, 5

When to check digoxin levels:

• Early during chronic therapy (after 5-7 days in normal renal function) 4
• When adding interacting medications 4, 3
• If signs or symptoms of toxicity appear 4, 3
• NOT routinely once stable dose established 4, 5

Special Clinical Scenarios

Advanced CKD with Hypotension:

Digoxin is particularly useful when hypotension limits beta-blocker use, as it does not lower blood pressure. 3

• For CrCl 17 mL/min: Start at 0.0625 mg daily or every other day 3
• Consider ultra-low-dose digoxin (0.03125 mg) combined with very low-dose beta-blocker 3
• Target serum concentration: 0.5-0.9 ng/mL 3

Elderly Patients:

The elderly have significantly prolonged digoxin half-life (69.6 vs 36.8 hours) and reduced clearance, requiring conservative dosing. 6

• Start at 0.0625-0.125 mg daily 1, 6
• Consider every-other-day dosing for those >80 years with any renal impairment 3
• Monitor more frequently due to altered pharmacokinetics 6

Common Pitfalls to Avoid

1. Do not use high doses (>0.25 mg daily) for rate control in atrial fibrillation—add beta-blocker instead 5
2. Do not routinely measure digoxin levels in stable patients—levels correlate poorly with therapeutic effect 5
3. Do not forget to reduce dose when adding amiodarone—failure to do so commonly causes toxicity 3, 9
4. Do not use loading doses in stable outpatients—unnecessary and increases toxicity risk 8, 5
5. Do not rely on digoxin alone for exercise rate control in AF—vagotonic effect is overcome by sympathetic activity 6, 7

Treatment of Digoxin Toxicity

For ventricular arrhythmias or severe bradycardia from digoxin toxicity, administer digoxin-specific Fab antibody fragments (DigiFab). 1, 8