Usage
- Digoxin is prescribed for heart failure (to improve symptoms and reduce hospitalizations) and certain types of irregular heartbeat like atrial fibrillation (to control heart rate and reduce the risk of blood clots).
- Pharmacological Classification: Cardiac glycoside, inotropic agent, antiarrhythmic agent.
- Mechanism of Action: Digoxin inhibits the sodium-potassium ATPase pump in heart cells, leading to increased intracellular calcium. This results in stronger heart contractions (positive inotropic effect) and slowed electrical conduction through the atrioventricular (AV) node (negative chronotropic effect).
Alternate Names
- No widely used alternate generic names.
- Brand Names: Lanoxin, Sigmaxin.
How It Works
- Pharmacodynamics: Digoxin increases the force of heart muscle contractions (positive inotropy) and slows the heart rate (negative chronotropy). It also increases vagal tone and decreases sympathetic activity.
- Pharmacokinetics:
- Absorption: Oral absorption varies (60-80% for tablets, 70-90% for elixir/solution).
- Distribution: Distributes widely in body tissues, including the heart. Volume of distribution decreases in renal impairment.
- Metabolism: Primarily excreted unchanged by the kidneys (70%), with minor metabolism in the liver and gut.
- Elimination: Renal excretion, with a half-life of 36-48 hours in adults with normal renal function (prolonged in renal impairment).
- Mode of Action: Digoxin inhibits the Na+/K+-ATPase pump in cardiac cell membranes. This leads to an increase in intracellular sodium, which reduces the activity of the sodium-calcium exchanger. Consequently, intracellular calcium levels rise, resulting in enhanced contractility.
- Receptor Binding/Enzyme Inhibition: Inhibits Na+/K+-ATPase.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Heart Failure: 0.125-0.25 mg orally once daily. Higher doses (up to 0.5 mg) are rarely needed. No loading dose is typically recommended for heart failure.
- Atrial Fibrillation: Initial loading dose of 0.5-1 mg orally or IV, divided over several doses. Maintenance dose: 0.125-0.5 mg orally once daily.
- Dose adjustments are crucial based on renal function, age, lean body mass, and serum digoxin levels.
Children:
- Dosage is based on body weight and age.
- Neonates (Preterm <1.5 kg): 25 mcg/kg over 24 hours, divided into doses.
- Neonates (Preterm 1.5-2.5 kg): 30 mcg/kg over 24 hours, divided into doses.
- Neonates (Term) to <5 years: 35 mcg/kg over 24 hours, divided into doses.
- 5-10 years: 25 mcg/kg over 24 hours, divided into doses.
- >10 years: Similar to adult dosing, adjusted for weight and renal function.
Special Cases:
- Elderly Patients: Lower starting dose (e.g., 0.125 mg/day) due to age-related decline in renal function.
- Patients with Renal Impairment: Dose reduction is necessary based on creatinine clearance.
- Patients with Hepatic Dysfunction: No major dose adjustment is typically required, but careful monitoring is essential.
- Patients with Comorbid Conditions: Dose adjustments may be needed depending on the specific comorbidity.
Clinical Use Cases
Digoxin is not typically indicated for routine use in intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like cardiac arrest. It may be considered in specific situations, such as managing atrial fibrillation or heart failure in these settings, but with cautious dosing and monitoring.
Dosage Adjustments
- Renal or hepatic dysfunction necessitates dose reduction.
- Electrolyte imbalances (especially hypokalemia, hypomagnesemia) can increase the risk of digoxin toxicity and require correction.
- Concomitant medications can interact with digoxin and necessitate dose adjustments (see Drug Interactions section).
Side Effects
Common Side Effects:
- Nausea, vomiting, diarrhea
- Loss of appetite
- Headache, dizziness, weakness
- Vision changes (blurred vision, yellow/green vision)
Rare but Serious Side Effects:
- Severe bradycardia (slow heart rate), heart block, arrhythmias
- Digoxin toxicity (see below)
Long-Term Effects:
- Chronic digoxin toxicity can occur with prolonged use at excessive doses.
Adverse Drug Reactions (ADR):
- Digoxin toxicity: Symptoms include anorexia, nausea, vomiting, diarrhea, confusion, weakness, vision changes, arrhythmias. Requires prompt medical attention.
Contraindications
- Ventricular fibrillation
- Hypersensitivity to digoxin or other digitalis glycosides
- Wolff-Parkinson-White syndrome with atrial fibrillation
Drug Interactions
Numerous drugs interact with digoxin. Some notable interactions include:
- Amiodarone, quinidine, verapamil: Increase digoxin levels.
- Antibiotics (clarithromycin, erythromycin): Increase digoxin levels.
- Antacids: Decrease digoxin absorption.
- Potassium-wasting diuretics (furosemide, thiazides): Can cause hypokalemia, increasing the risk of digoxin toxicity.
- Spironolactone: Can alter digoxin pharmacokinetics.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (oral), not assigned (injectable).
- Digoxin crosses the placenta. Monitor neonates for toxicity after in-utero exposure.
- Digoxin is excreted in breast milk in small amounts, generally considered safe for breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits Na+/K+-ATPase, increasing intracellular calcium and leading to stronger heart contractions and slower heart rate.
- Side Effects: Nausea, vomiting, diarrhea, headache, dizziness, vision changes, arrhythmias, digoxin toxicity.
- Contraindications: Ventricular fibrillation, hypersensitivity, WPW syndrome with atrial fibrillation.
- Drug Interactions: Amiodarone, quinidine, verapamil, antibiotics, antacids, diuretics.
- Pregnancy & Breastfeeding: Generally safe with careful monitoring.
- Dosage: Variable based on indication, age, renal function, and other factors.
- Monitoring Parameters: Serum digoxin levels, renal function, electrolytes (especially potassium), heart rate and rhythm.
Popular Combinations
- Digoxin is often used in combination with other heart failure medications such as ACE inhibitors, beta-blockers, and diuretics.
- For atrial fibrillation, it can be combined with beta-blockers or calcium channel blockers for better rate control.
Precautions
- Careful monitoring of serum digoxin levels, renal function, and electrolytes.
- Patients with renal impairment, hypothyroidism, or electrolyte imbalances require close monitoring.
- Avoid concomitant medications that can interact with digoxin.
- Monitor for signs of digoxin toxicity.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Digoxin?
A: Dosage is highly individualized. It varies based on age, weight, renal function, indication (heart failure or atrial fibrillation), and other patient-specific factors. Consult dosing guidelines and monitor serum digoxin levels.
Q2: How is digoxin toxicity diagnosed and managed?
A: Diagnosis involves evaluating symptoms (nausea, vomiting, vision changes, arrhythmias), serum digoxin levels, and electrolyte imbalances. Management includes discontinuing digoxin, correcting electrolyte abnormalities, and potentially using digoxin-specific antibody fragments (Digibind) in severe cases.
Q3: What are the key drug interactions to be aware of with digoxin?
A: Amiodarone, quinidine, verapamil, certain antibiotics (clarithromycin, erythromycin), antacids, and potassium-wasting diuretics can significantly interact with digoxin, altering its levels or effects. Consult drug interaction resources for a comprehensive list.
Q4: Can digoxin be used in pregnant or breastfeeding women?
A: Digoxin can be used cautiously in pregnant and breastfeeding women if the benefits outweigh the risks. Monitor serum digoxin levels and observe neonates for potential toxicity.
Q5: How does renal impairment affect digoxin dosing?
A: Renal impairment reduces digoxin clearance, necessitating dose reduction to avoid toxicity. Adjust the dose based on creatinine clearance.
Q6: What are the therapeutic serum digoxin levels?
A: Therapeutic range is generally 0.5-2 ng/mL, although toxic effects can occur at lower concentrations. Some guidelines recommend lower target ranges (0.5-0.9 ng/mL), especially for atrial fibrillation and heart failure patients in sinus rhythm.
Q7: What are the common signs and symptoms of digoxin toxicity?
A: Anorexia, nausea, vomiting, diarrhea, confusion, weakness, vision changes (blurred vision, yellow/green halos), and various arrhythmias are common signs and symptoms of digoxin toxicity.
Q8: What is the role of monitoring potassium levels in patients on digoxin?
A: Hypokalemia can increase the risk of digoxin toxicity. Therefore, potassium levels should be monitored and corrected if necessary.
Q9: Are there any specific dietary considerations for patients taking digoxin?
A: High-fiber foods may decrease digoxin absorption. Consistent timing of meals is recommended. Avoid excessive consumption of black licorice, which can interact with digoxin and potentially cause electrolyte imbalances.
