Digoxin

Digoxin is a time-tested cardiac glycoside derived from the foxglove plant (Digitalis lanata), prescribed primarily for the management of specific cardiac arrhythmias and heart failure. It functions by inhibiting the sodium-potassium ATPase pump, leading to increased intracellular calcium, which enhances myocardial contractility (positive inotropy). Additionally, it exerts vagomimetic effects on the atrioventricular (AV) node, slowing conduction and reducing ventricular rate in atrial tachyarrhythmias. Its narrow therapeutic index necessitates careful dosing and vigilant therapeutic drug monitoring to maximize efficacy while minimizing the risk of toxicity.

Features

• Active Ingredient: Digoxin
• Standard Formulations: Oral tablets (62.5 mcg, 125 mcg, 250 mcg), intravenous injection (100 mcg/mL, 250 mcg/mL)
• Pharmacologic Class: Cardiac glycoside
• Mechanism of Action: Inhibition of Na⁺/K⁺-ATPase pump, leading to increased intracellular sodium and calcium, enhanced cardiac contractility, and slowed AV nodal conduction
• Bioavailability: Oral bioavailability ranges from 60% to 80% (tablets)
• Protein Binding: Approximately 25%
• Half-Life: 36–48 hours in patients with normal renal function; prolonged in renal impairment
• Therapeutic Range: 0.5–2.0 ng/mL (narrow therapeutic window)
• Primary Excretion: Renal (unchanged)

Benefits

• Provides precise control of ventricular rate in patients with atrial fibrillation and atrial flutter, improving exercise tolerance and reducing symptoms of palpitations
• Augments myocardial contractility in systolic heart failure, leading to improved cardiac output, reduced pulmonary congestion, and alleviation of symptoms such as dyspnea and fatigue
• Offers flexible dosing regimens with both oral and intravenous formulations suitable for inpatient and long-term outpatient management
• May reduce hospitalizations for heart failure exacerbations when used as part of a guideline-directed medical therapy regimen
• Long history of clinical use with well-characterized pharmacokinetics and established monitoring parameters

Common use

Digoxin is indicated for the treatment of mild to moderate heart failure with reduced ejection fraction (HFrEF), particularly in patients who remain symptomatic despite treatment with ACE inhibitors, beta-blockers, and diuretics. It is also widely used for rate control in permanent, persistent, or paroxysmal atrial fibrillation and atrial flutter, especially when other rate-controlling agents (such as beta-blockers or calcium channel blockers) are contraindicated, poorly tolerated, or insufficient. Its use is generally reserved for specific patient populations due to its narrow therapeutic index and potential for significant drug interactions.

Dosage and direction

Dosing must be individualized based on lean body weight, renal function, age, and concomitant medications. A loading dose (digoxin priming) may be used in urgent situations: typically 10–15 mcg/kg ideal body weight administered in divided doses (50% initially, then 25% every 6–8 hours) with careful monitoring. Maintenance dosing for adults with normal renal function (CrCl >50 mL/min) is usually 125–250 mcg once daily. For elderly patients or those with renal impairment (CrCl 10–50 mL/min), doses of 62.5 mcg daily or 125 mcg every other day are common. Serum digoxin levels should be measured at least 6–8 hours post-dose, with a target therapeutic range of 0.5–2.0 ng/mL. IV administration should be slow, over at least 5 minutes, and preferably with EKG monitoring.

Precautions

Digoxin has a narrow therapeutic index; toxicity can occur even at therapeutic doses, particularly in the elderly, patients with renal impairment, electrolyte disturbances (hypokalemia, hypomagnesemia, hypercalcemia), hypoxia, or thyroid disorders. Renal function should be assessed before initiation and periodically during therapy. Concomitant use of drugs that affect renal function or interact with digoxin (e.g., diuretics, amiodarone, verapamil) requires dose adjustment and closer monitoring. Patients should be educated to recognize early signs of toxicity such as nausea, vomiting, visual disturbances (e.g., yellow-green halos), and confusion.

Contraindications

Digoxin is contraindicated in patients with ventricular fibrillation or known hypersensitivity to digoxin or other digitalis preparations. It should not be used in patients with Wolff-Parkinson-White (WPW) syndrome and atrial fibrillation, due to risk of paradoxical acceleration of ventricular response. Additional contraindications include second- or third-degree heart block (without a permanent pacemaker), idiopathic hypertrophic subaortic stenosis (IHSS), and constrictive pericarditis. Caution is advised in amyloid heart disease and constrictive cardiomyopathies.

Possible side effect

Common adverse effects include nausea, vomiting, diarrhea, headache, dizziness, and fatigue. Cardiac effects may include bradycardia, AV block, premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, or fibrillation. Non-cardiac toxic effects can manifest as visual disturbances (chromatopsia, photophobia, blurred vision), confusion, nightmares, agitation, and (rarely) gynecomastia in males. Chronic use may rarely lead to digoxin toxicity even with previously stable serum levels, particularly if renal function declines.

Drug interaction

Digoxin interacts significantly with numerous medications. Amiodarone, verapamil, diltiazem, quinidine, and propafenone can increase digoxin serum levels. Concomitant use with diuretics (especially loop and thiazide diuretics) increases the risk of hypokalemia, potentiating digoxin toxicity. Macrolide antibiotics, tetracyclines, and omeprazole may increase bioavailability. Concomitant use with sympathomimetics, succinylcholine, or thyroid hormones may increase the risk of arrhythmias. Calcium preparations administered IV may precipitate serious arrhythmias in digoxin-treated patients.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. However, if it is near the time for the next dose, the missed dose should be skipped. Doubling the dose to compensate for a missed dose is not recommended due to the risk of toxicity. Patients should be advised to maintain a consistent dosing schedule and to inform their healthcare provider if multiple doses are missed.

Overdose

Digoxin overdose is a medical emergency and can be fatal. Symptoms include severe nausea, vomiting, hyperkalemia, visual changes, confusion, and life-threatening arrhythmias (e.g., ventricular tachycardia, advanced heart block). Management includes immediate discontinuation of digoxin, ECG monitoring, correction of electrolyte imbalances (especially potassium), and administration of digoxin-specific antibody fragments (Digibind®) for severe or life-threatening toxicity. Activated charcoal may be beneficial if administered shortly after ingestion. Hemodialysis is not effective due to high volume of distribution.

Storage

Store at controlled room temperature (20°–25°C or 68°–77°F). Protect from light and moisture. Keep in the original container, tightly closed. Do not store in bathrooms or damp areas. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging.

Disclaimer

This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting, changing, or discontinuing any medication. Dosage and indications may vary based on individual patient factors, clinical context, and updated medical guidelines. The author and publisher are not liable for any adverse effects resulting from the use or misuse of this information.

Reviews

“Digoxin remains a valuable agent in my practice for rate control in atrial fibrillation, especially in elderly patients with contraindications to beta-blockers. Its inotropic effect is also useful in advanced heart failure, though it requires meticulous monitoring.” — Cardiologist, 15 years experience
“While newer agents have emerged, digoxin’s cost-effectiveness and oral bioavailability make it a practical choice in resource-limited settings. However, the narrow therapeutic window demands vigilance.” — Internal Medicine Specialist
“Patient education is critical. Those who understand the signs of toxicity adhere better and report symptoms early, preventing serious complications.” — Clinical Pharmacist
“I use it cautiously in patients with renal impairment. Regular creatinine checks and dose adjustments are non-negotiable.” — Nephrologist
“A classic drug that still has a place in modern cardiology, but respect for its potential toxicity is paramount.” — Senior Cardiology Fellow