Digoxin

# Digoxin ## Overview - **Classification**: Cardiac glycoside; antiarrhythmic (Class IV). - **Mechanism**: Inhibits Na+/K+-ATPase, increasing intracellular Ca++. This enhances myocardial contractility (positive inotropy) and decreases AV node conduction (negative chronotropy). ## Primary Indications 1. **Heart Failure (HF)** - To improve symptoms and exercise tolerance in chronic HFrEF when standard therapies are insufficient. 2. **Atrial Fibrillation (AFib)** - For ventricular rate control in patients with chronic AFib, especially when accompanied by HF. 3. **Atrial Flutter** - For ventricular rate control. ## Adult Dosing ### Standard Dosing **Heart Failure (HFrEF)** - **Maintenance Dose**: **0.125-0.25 mg** - **Frequency**: Once daily - **Route**: Oral (tablet, elixir), Intravenous - **Target Level**: **0.5-0.9 ng/mL** (lower end of therapeutic range for HF). **Atrial Fibrillation/Flutter (Rate Control)** - **Loading Dose (Optional)**: **0.5-1 mg** PO/IV total, divided over 24 hours (e.g., **0.25-0.5 mg** initially, then **0.25 mg** q6-8h x 2). - **Maintenance Dose**: **0.125-0.25 mg** - **Frequency**: Once daily - **Route**: Oral (tablet, elixir), Intravenous - **Target Level**: **0.8-2 ng/mL** (for rate control). ### Dose Adjustments - **Renal Impairment**: Reduce dose by 25-50% or extend interval. - CrCl 10-50 mL/min: Give **25-75%** of usual daily dose or dose every 36 hours. - CrCl < 10 mL/min: Give **10-25%** of usual daily dose or dose every 48 hours. - Monitor levels closely. - **Hepatic Impairment**: No specific dose adjustment needed; primarily renally eliminated. - **Elderly Patients**: Start with lower doses (**0.125 mg** daily or every other day) due to potential for decreased renal function and increased sensitivity. Monitor closely. ## Pediatric Dosing **Note**: Dosing is complex, highly individualized, and requires close monitoring. IV doses are 75% of oral doses. ### Neonates (0-28 days) - **Total Digitalizing Dose (TDD) Oral**: - Premature (1-1500g): **15-20 mcg/kg** TDD - Premature (1500-2500g): **20-30 mcg/kg** TDD - Full-term (>2500g): **25-35 mcg/kg** TDD - **Frequency**: TDD given as 50% initial dose, then 25% q6-12h x 2. - **Maintenance Dose**: **25-30%** of TDD daily, divided BID. - **Maximum**: Specific to weight, based on TDD. - **Special Notes**: Extremely narrow therapeutic window. Monitor serum levels, ECG, and clinical status closely. ### Infants (1-12 months) - **Total Digitalizing Dose (TDD) Oral**: **35-60 mcg/kg** TDD - **Frequency**: TDD given as 50% initial dose, then 25% q6-12h x 2. - **Maintenance Dose**: **25-35%** of TDD daily, divided BID. - **Maximum**: TDD not to exceed **1 mg**. - **Special Notes**: Higher dose/kg due to larger volume of distribution compared to adults. ### Children (1-12 years) - **Total Digitalizing Dose (TDD) Oral**: **30-50 mcg/kg** TDD - **Frequency**: TDD given as 50% initial dose, then 25% q6-12h x 2. - **Maintenance Dose**: **25-35%** of TDD daily, divided BID. - **Maximum**: TDD not to exceed **1 mg**. Maintenance not to exceed **0.5 mg/day**. ### Adolescents (13-18 years) - **Dose**: Approach adult dosing, typically **0.125-0.25 mg** PO. - **Frequency**: Once daily. - **Maximum**: **0.25 mg/day** maintenance. - **Special Notes**: Use adult guidelines for initial dosing and adjustments. ## Safety Information ### Contraindications - **Absolute**: Ventricular fibrillation (VFib). - **Absolute**: Digoxin toxicity. - **Absolute**: High-output HF (e.g., hyperthyroidism, beriberi heart). - **Absolute**: Wolff-Parkinson-White (WPW) syndrome with AFib/flutter. - **Absolute**: Second- or third-degree AV block in absence of pacemaker. - **Relative**: Electrolyte imbalances (hypokalemia, hypomagnesemia, hypercalcemia) increase toxicity risk. ### Common Adverse Effects - **Very Common (>10%)**: Nausea, vomiting, anorexia, diarrhea. - **Common (1-10%)**: Dizziness, headache, fatigue, visual disturbances (yellow-green halos, blurred vision). - **Serious but Rare**: Cardiac arrhythmias (bradycardia, AV block, ventricular tachycardia/fibrillation), severe GI upset, thrombocytopenia. - **Serious but Rare**: Digoxin toxicity (often preceded by GI/CNS symptoms, then cardiac arrhythmias). ### Key Drug Interactions - **Amiodarone, Verapamil, Diltiazem, Quinidine, Macrolides**: Increase digoxin levels. Reduce digoxin dose by 25-50% when starting these. - **Loop and Thiazide Diuretics**: May cause hypokalemia, increasing digoxin toxicity risk. Monitor electrolytes. - **Beta-blockers, Calcium Channel Blockers**: Synergistic effect on AV nodal blockade, increasing bradycardia/AV block risk. Monitor HR, ECG. - **P-glycoprotein Inducers (e.g., Rifampin, Phenytoin)**: Decrease digoxin levels. May need to increase digoxin dose. - **Antacids, Cholestyramine**: Decrease digoxin absorption. Separate administration times by several hours. ## Monitoring & Follow-up - **Before Treatment**: Baseline ECG, serum electrolytes (K+, Mg++, Ca++), renal function (BUN, Cr), LFTs. - **During Treatment**: Serum digoxin levels (draw 6-8 hours post-dose, ideally pre-dose). - **During Treatment**: Renal function, electrolytes, ECG (regularly or if toxicity suspected). - **Clinical Signs**: Monitor for signs/symptoms of toxicity (anorexia, nausea, vomiting, visual changes, new arrhythmias, severe fatigue). ## Clinical Pearls - 💡 **Therapeutic Range**: HF target **0.5-0.9 ng/mL**; AFib target **0.8-2 ng/mL**. Toxicity can occur at any level. - 💡 **Antidote**: Digoxin immune Fab (DigiFab) is available for life-threatening toxicity. - 💡 **Electrolytes**: Always correct hypokalemia and hypomagnesemia before or during digoxin therapy to prevent toxicity. - 💡 **Administration**: Administer oral digoxin without regard to food, but separate from antacids by several hours. - 💡 **Patient Counseling**: Educate patients on symptoms of toxicity and importance of adherence. Avoid abrupt discontinuation. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.