Digoxin is a time-tested cardiac glycoside medication derived from the foxglove plant (Digitalis lanata). It remains a cornerstone in the management of various heart conditions, primarily for its positive inotropic effects (increasing the force of myocardial contraction) and negative chronotropic effects (decreasing heart rate). This agent is specifically indicated for the treatment of heart failure with reduced ejection fraction and for controlling ventricular rate in patients with atrial fibrillation. Its mechanism of action involves inhibition of the sodium-potassium ATPase pump, leading to increased intracellular calcium, which enhances cardiac contractility. Careful therapeutic drug monitoring is essential due to its narrow therapeutic index.

Features

• Active Ingredient: Digoxin
• Drug Class: Cardiac Glycoside
• Available Forms: Oral tablets (62.5 mcg, 125 mcg, 250 mcg), Oral solution (50 mcg/mL), Injectable solution for IV or IM administration (100 mcg/mL, 250 mcg/mL)
• Bioavailability: Approximately 60-80% for tablets (formulation-dependent), 70-85% for elixir
• Onset of Action: Oral: 1-2 hours; IV: 5-30 minutes
• Time to Peak Effect: Oral: 2-6 hours; IV: 1-4 hours
• Therapeutic Half-life: 36-48 hours in patients with normal renal function (prolonged in renal impairment)
• Primary Elimination: Renal excretion (unchanged)
• Therapeutic Serum Concentration Range: 0.5 - 2.0 ng/mL (Target often 0.5-0.9 ng/mL for heart failure; 0.8-1.2 ng/mL for atrial fibrillation)

Benefits

• Improves Cardiac Output: Enhances the strength of heart muscle contractions, allowing the heart to pump blood more effectively throughout the body, alleviating symptoms of heart failure like fatigue and shortness of breath.
• Controls Ventricular Rate: Effectively slows down the heart rate in patients with atrial fibrillation or atrial flutter, improving ventricular filling and coronary perfusion.
• Reduces Hospitalizations: Long-term use in appropriate patients with heart failure has been associated with a reduction in symptoms and hospitalizations due to heart failure exacerbations.
• Provides Symptomatic Relief: Helps alleviate clinical signs of heart failure, including orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema.
• Oral Administration: Available in convenient oral formulations for long-term outpatient management.

Common use

Digoxin is primarily used for two main indications:

1. Heart Failure with Reduced Ejection Fraction (HFrEF): Used as an adjunctive therapy to guideline-directed medical therapy (e.g., ACE inhibitors, ARBs, ARNIs, beta-blockers, MRAs) to improve symptoms, increase exercise tolerance, and reduce hospitalizations in patients with symptomatic HFrEF.
2. Atrial Fibrillation/Flutter: Used for long-term rate control in patients with chronic atrial fibrillation or atrial flutter. It is particularly useful in patients with concomitant heart failure or sedentary patients.

It is not typically a first-line agent for either condition but serves as a valuable addition to the treatment regimen when standard therapies are insufficient or contraindicated.

Dosage and direction

Dosing is highly individualized based on the patient’s age, weight, renal function, and clinical indication. A loading dose (digoxin loading) is sometimes used to achieve a therapeutic effect more rapidly, but maintenance dosing is more common.

• Dosing Principle: Dose must be adjusted for renal impairment. Creatinine clearance (CrCl) must be calculated (e.g., using Cockcroft-Gault formula).
• Heart Failure (Maintenance Dosing): The recommended usual dose is 125 mcg or 250 mcg once daily. A dose of 125 mcg daily is often preferred in older patients or those with impaired renal function. Dosing is typically based on lean body weight.
• Atrial Fibrillation (Maintenance Dosing): The target is control of the ventricular rate at rest. The typical dose is 125 mcg to 375 mcg once daily.
• Administration: Oral tablets should be taken consistently with respect to meals. The elixir should be measured carefully with the supplied dropper.
• Monitoring: Serum digoxin concentrations should be measured at least 6-8 hours after the last dose, once steady state is reached (which may take over a week). Trough levels are drawn immediately before the next dose.

Never initiate or adjust a digoxin dose without direct supervision by a qualified healthcare professional.

Precautions

• Narrow Therapeutic Index: Digoxin has a very small margin between therapeutic and toxic doses. Meticulous dosing and monitoring are mandatory.
• Renal Impairment: Digoxin is primarily excreted by the kidneys. Dosage must be reduced in patients with renal insufficiency (low CrCl). Renal function should be assessed regularly.
• Electrolyte Imbalances: Hypokalemia, hypomagnesemia, and hypercalcemia predispose patients to digoxin toxicity, even at “normal” serum levels. These electrolytes must be monitored and corrected.
• Thyroid Disorders: Both hypothyroidism and hyperthyroidism can alter sensitivity to digoxin. Thyroid function should be evaluated.
• Underlying Heart Disease: Pre-existing ventricular arrhythmias or AV block can be exacerbated.
• Pregnancy (Category C): Digoxin crosses the placenta. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Breastfeeding: Digoxin is excreted in breast milk, but amounts are likely too small to be harmful. Use with caution.

Contraindications

Digoxin is contraindicated in patients with:

• Ventricular fibrillation.
• Known hypersensitivity to digoxin or other digitalis preparations.
• Second-degree or third-degree AV block (in the absence of a functioning permanent pacemaker).
• Wolff-Parkinson-White (WPW) syndrome with atrial fibrillation (increases risk of life-threatening ventricular arrhythmias).
• Constrictive pericarditis or cardiac amyloidosis.
• Idiopathic hypertrophic subaortic stenosis (IHSS).

Possible side effect

Side effects are often dose-related and may be early signs of toxicity.

• Common: Nausea, vomiting, diarrhea, headache, dizziness, fatigue, visual disturbances (e.g., yellow-green halos around objects, blurred vision).
• Cardiac (Toxic): New arrhythmias are the most serious concern. These include PVCs, ventricular bigeminy/trigeminy, ventricular tachycardia, atrial tachycardia with block, junctional tachycardia, and advanced heart block. Any new cardiac symptom requires immediate evaluation.
• Neurological: Confusion, insomnia, nightmares, agitation, psychosis (rare).
• Gynecomastia: Can occur with long-term use.

Drug interaction

Digoxin interacts with a wide range of medications:

• Diuretics: Loop and thiazide diuretics can cause hypokalemia, increasing the risk of toxicity.
• Amiodarone, Quinidine, Verapamil, Diltiazem, Propafenone: These drugs can significantly increase serum digoxin concentrations by reducing its renal or non-renal clearance. A 50% reduction in the digoxin dose is often required when starting amiodarone or quinidine.
• Macrolide Antibiotics (e.g., Erythromycin), Tetracyclines: Can increase digoxin levels by altering gut flora (some digoxin is metabolized by bacteria in the intestine).
• Antacids, Kaolin-pectin, Cholestyramine, Colestipol: Can decrease the absorption of oral digoxin. Doses should be separated by several hours.
• Sympathomimetics (e.g., Albuterol): Can increase the risk of cardiac arrhythmias.
• Succinylcholine: May potentiate arrhythmogenic effects.
• Thyroid Hormones: May decrease serum digoxin levels.

Missed dose

• If a dose is missed, it should be taken as soon as it is remembered on the same day.
• If it is almost time for the next dose, skip the missed dose and resume the usual dosing schedule.
• Do not double the dose to make up for a missed one.
• If multiple doses are missed, contact a healthcare provider for guidance, as re-titration may be needed.

Overdose

Digoxin overdose is a life-threatening medical emergency.

• Symptoms: Severe nausea and vomiting, hyperkalemia, profound bradycardia, severe visual disturbances, and any of the cardiac arrhythmias listed under side effects.
• Treatment:
  • Immediate Action: Call emergency services (e.g., 911).
  • GI Decontamination: Activated charcoal may be administered if ingestion was recent.
  • Cardiac Monitoring: Continuous ECG monitoring is essential.
  • Digoxin Immune Fab (Digibind®/DigiFab®): This is the specific antidote for serious, life-threatening digoxin toxicity. It binds digoxin molecules, rendering them inactive.
  • Symptomatic Management: Correction of electrolyte abnormalities (e.g., potassium, magnesium). Antiarrhythmic drugs (e.g., phenytoin, lidocaine) may be used with caution. Atropine or temporary pacing may be needed for bradycardia.

Storage

• Store at room temperature (20°C to 25°C or 68°F to 77°F).
• Keep the container tightly closed.
• Protect from light and moisture.
• Keep out of reach of children and pets.
• Do not flush medications down the toilet or pour them into a drain. Dispose of unused medication through a official medicine take-back program.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any errors or omissions or for any consequences from the application of this information.

Reviews

• “As a cardiologist for over 30 years, digoxin remains a vital tool in my arsenal for select patients with difficult-to-control AFib and advanced HF. Its efficacy is undeniable, but it demands the utmost respect for its narrow therapeutic window. Careful patient selection and vigilant monitoring are non-negotiable.” – Dr. A. Reynolds, MD, Cardiology
• “Managing my father’s heart failure has been a journey. Adding digoxin to his regimen was a turning point. His breathing improved noticeably within a few weeks, and he has had fewer ‘bad days’. We are very diligent about his blood tests.” – Family Caregiver
• “From a clinical pharmacy perspective, digoxin is a classic example of a drug where pharmacokinetics are paramount. Dosing based on renal function and being aware of its extensive drug interaction profile is critical to preventing adverse events and ensuring therapeutic success.” – Clinical Pharmacist Specialist
• “I’ve been on digoxin for my atrial fibrillation for five years. It has successfully kept my heart rate in check. The only issue was some nausea when I first started, but it went away after my dose was slightly lowered.” – Patient