Digoxin

• Approved Indications:
• Heart Failure: Adjunctive treatment in heart failure with reduced ejection fraction to improve symptoms and reduce hospitalizations
• Atrial Fibrillation and Atrial Flutter: Control of ventricular rate, especially in chronic atrial fibrillation
• Supraventricular Tachyarrhythmias: Management of certain supraventricular arrhythmias
• Off-label/Clinically Accepted Uses:
• Rate control in patients with atrial fibrillation with concomitant heart failure
• Occasionally used in certain pediatric arrhythmias under specialist guidance

• Route: Oral (tablets or solution), intravenous (IV) injection
• Adults:
• Loading Dose (if needed): 0.5 mg followed by 0.25 mg every 6–8 hours up to a total loading dose of 1–1.5 mg in 24 hours (IV only)
• Maintenance Dose: Typically 0.125–0.25 mg once daily orally; individualized based on clinical response and serum levels
• Pediatrics:
• Dose based on body weight and clinical indication, usually 10–15 mcg/kg/day divided into 2 doses
• Elderly:
• Start at lower maintenance doses (e.g., 0.125 mg daily or less) due to decreased clearance and increased sensitivity
• Renal Impairment:
• Dose adjustments required as digoxin is primarily renally excreted; monitor serum digoxin levels and renal function regularly
• Hepatic Impairment:
• No significant dosage adjustment needed, but monitor clinical response
• Administration Notes:
• Oral tablets can be taken with or without food
• IV administration should be slow (over at least 5 minutes) to avoid toxicity

Digoxin is a cardiac glycoside that inhibits the sodium-potassium ATPase pump in myocardial cells, leading to increased intracellular sodium. This increase reduces the activity of the sodium-calcium exchanger, resulting in elevated intracellular calcium concentrations. The higher intracellular calcium enhances cardiac muscle contractility (positive inotropic effect). Additionally, digoxin increases vagal (parasympathetic) tone, which slows conduction through the atrioventricular (AV) node and decreases heart rate (negative chronotropic effect), beneficial in controlling ventricular response in atrial fibrillation.

• Absorption: Well absorbed orally, with bioavailability approximately 60–80% (higher for tablets and capsules than liquid forms)
• Distribution: Widely distributed in body tissues, especially heart, skeletal muscle, liver, and kidneys; volume of distribution approx. 5–7 L/kg
• Metabolism: Minimal hepatic metabolism; majority of drug remains unchanged
• Half-life: Approximately 36–48 hours in patients with normal renal function; prolonged in renal impairment
• Elimination: Primarily renal excretion as unchanged drug; about 50–70% eliminated unchanged in urine
• Onset of Action: Oral: 30 minutes to 2 hours; IV: within 5 to 30 minutes
• Steady State: Achieved in 5–7 days with maintenance dosing

• Pregnancy:
• FDA Category C — Animal studies have shown adverse effects; no adequate well-controlled studies in humans
• Use only if potential benefit justifies potential risk to fetus
• Lactation:
• Excreted in breast milk in small amounts; generally considered compatible with breastfeeding but monitor infant for toxicity signs

• Primary Class: Cardiac glycoside
• Subclass: Positive inotropic agent, antiarrhythmic (Class V, vagomimetic)

• Known hypersensitivity to digoxin or any component of the formulation
• Ventricular fibrillation
• Digitalis toxicity or overdose
• Certain ventricular arrhythmias such as ventricular tachycardia without concomitant heart failure treatment
• WPW syndrome with atrial fibrillation

• Narrow therapeutic index—risk of toxicity even at therapeutic doses
• Monitor serum digoxin levels, renal function, and electrolytes regularly (especially potassium, magnesium, calcium)
• Caution in hypokalemia, hypomagnesemia, or hypercalcemia as these increase toxicity risk
• Use cautiously in patients with AV block without pacemaker
• Bradycardia and other arrhythmias can be precipitated by digoxin
• Adjust dose in renal impairment and elderly
• Avoid abrupt discontinuation in patients with heart failure

• Common:
• Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain
• CNS: headache, dizziness, fatigue, confusion, visual disturbances (e.g., blurred vision, yellow-green halos)
• Cardiovascular: bradycardia, arrhythmias, palpitations
• Serious/Rare:
• Life-threatening arrhythmias (ventricular tachycardia/fibrillation, heart block)
• Digitalis toxicity syndrome including severe CNS and cardiac effects

• Major Interactions:
• Diuretics (especially loop and thiazide) may cause hypokalemia, increasing digoxin toxicity risk
• Amiodarone, verapamil, quinidine, and other P-glycoprotein inhibitors increase digoxin serum levels
• Rifampin and St. John’s Wort may decrease digoxin levels by inducing P-glycoprotein
• Beta-blockers and calcium channel blockers can have additive effects on AV node conduction
• Enzyme Systems:
• Not significantly metabolized by CYP450 but affected by P-glycoprotein transport

• Recent heart failure guidelines recommend digoxin as a second-line agent for symptom control in select patients with heart failure with reduced ejection fraction
• Emphasis on careful monitoring of drug levels and electrolytes to prevent toxicity
• Updated recommendations suggest limited use in atrial fibrillation when rate control can be achieved with safer agents
• Increased awareness of drug interactions and risk factors for toxicity in elderly and renal-impaired patients

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Keep tablets in original container tightly closed
• Keep out of reach of children