Rapid digitalization with a loading dose: 400 to 600 mcg (0.4 to 0.6 mg) IV 500 to 750 mcg (0.5 to 0.75 mg) PO as a single dose; additional doses of 100 to 300 mcg (0.1 to 0.3 mg) or 125 to 375 mcg (0.125 to 0.375 mg) PO may be given cautiously at 6- to 8-h intervals until clinical evidence of an adequate effect is noted.
Gradual digitalization with a maintenance dose: Initial dosage of 250 mcg (0.25 mg) PO once daily. Increase doses every 2 wk according to clinical response. Usual maintenance dosage is 125 to 500 mcg (0.125 to 0.5 mg) PO once daily.
American College of Cardiology/American Heart Association (ACC/AHA) guidelines: Loading dose not needed. Initial and maintenance dosage is 125 mcg (0.125 mg) to 250 mcg (0.25 mg) daily.
Infants and Children: Individualize dosage. Usual doses are listed in the previous section.
Elderly: Initial dosage of 125 mcg (0.125 mg) once daily for treatment of heart failure. Per ACC/AHA guidelines, the initial dosage is 125 mcg (0.125 mg) daily or every other day.
Renal function impairment: Initial dosage of 125 mcg (0.125 mg) once daily; 62.5 mcg (0.625 mg) once daily in patients with marked renal impairment. Per ACC/AHA guidelines, the initial dosage is 125 mcg (0.125 mg) daily or every other day.
Low lean body mass: Per ACC/AHA guidelines, the initial dosage is 125 mcg (0.125 mg) daily or every other day.
Infants and Children:
|Usual Pediatric Digitalizing and Maintenance Dosages With Healthy Renal Function Based on Lean Body Weight|
|Age||Digitalizing dose (mcg/kg)||Daily maintenance dose as % of loading dose (mcg/kg in 2 to 3 divided doses)|
|Premature||20 to 30||15 to 25||20% to 30%|
|Term||25 to 35||20 to 30||25% to 35%|
|1 to 24 mo||35 to 60||30 to 50||25% to 35%|
|2 to 5 yr||30 to 40||25 to 35||25% to 35%|
|5 to 10 yr||20 to 35||15 to 30||25% to 35%|
|> 10 yr||10 to 15||8 to 12||25% to 35%|
Adults: Peak digoxin body stores greater than 8 to 12 mcg/kg are usually required. Titrate doses to the minimum dose. The following dosages are according to ACC/AHA guidelines.
Acute setting: Loading dose of 250 mcg (0.25 mg) IV every 2 h (up to 1,500 mcg [1.5 mg]) (onset at least 60 min) followed by a maintenance dosage of 125 to 375 mcg (0.125 to 0.375 mg) daily IV or PO.
Nonacute setting: Loading dose of 500 mcg (0.5 mg) daily PO (onset 2 days) followed by a maintenance dosage of 125 to 375 mcg (0.125 to 0.375 mg) daily PO .
|•||Calculate doses based upon lean (ideal) body weight.|
|•||Consider the differences in bioavailability between digoxin injection, tablets, and oral solution when changing patients from one dosage form to another. See Pharmacokinetics.|
|•||For IV administration, digoxin injection may be diluted (4-fold or more) with normal saline, dextrose 5% in water, or sterile water for injection. Infuse slowly, 5 min or longer.|
|•||IM injection can lead to severe pain at the injection site. If the drug must be administered IM, inject it deeply into the muscle and follow with massage. Do not inject more than 2 mL into a single site.|
Increases force and velocity of myocardial systolic contraction (positive inotropic action), slows heart rate, decreases conduction velocity through AV node, and decreases the degree of activation of the sympathetic nervous system and renin-angiotensin system.
All actions are mediated through effects on sodium-potassium ATPase.
Ventricular fibrillation; hypersensitivity to digoxin or to other digitalis preparations.
Use Cautiously in:
|•||Hypokalemia (greatly increases risk of digoxin toxicity).|
|•||Hypercalcemia (increases risk of toxicity, especially with mild hypokalemia).|
|•||Hypomagnesemia (may potentiate digoxin toxicity).|
|•||Diuretic use (may cause electrolyte abnormalities including hypokalemia and hypomagnesemia).|
|•||Geri: Geriatric patients (very sensitive to toxic effects, dose adjustments required for age-related decrease in renal function and body weight).|
|•||Renal impairment (dose reduction required).|
|•||Obesity (dose should be based on ideal body weight).|
|•||OB: Pregnancy (although safety has not been established, has been used during pregnancy without adverse effects on the fetus);Lactation: Similar concentrations in serum and breast milk result in subtherapeutic levels in infant, use with caution).|
Mental disturbances (4.1%)
Maculopapular rash (1.6%)
Arrhythmia in children (consider a toxicity)
Visual disturbance (blurred or yellow vision)
Heart block (1°/2°/3°)
Acarbose, albuterol, antineoplastic agents (ie, bleomycin, carmustine, cyclophosphamide, cytarabine, doxorubicin, methotrexate, vincristine), penicillamine, rifamycins (eg, rifampin), sulfasalazine
Digoxin serum concentrations may be reduced, decreasing the efficacy. Monitor digoxin serum concentrations and adjust the dose as needed.
Alprazolam, antiarrhythmic agents (ie, amiodarone, propafenone, quinidine), azole antifungal agents (ie, itraconazole, ketoconazole), calcium channel blockers (ie, diltiazem, nifedipine, verapamil), carvedilol, conivaptan, cyclosporine, epoprostenol, gatifloxacin, macrolide antibiotics (eg, clarithromycin, erythromycin), nefazodone, NSAIDs (eg, diclofenac, ibuprofen, indomethacin), protease inhibitors (ie, ritonavir, saquinavir), proton pump inhibitors (eg, lansoprazole, omeprazole, rabeprazole), quinine, ranolazine, serotonin reuptake inhibitors (eg, fluoxetine, paroxetine, sertraline), telithromycin, telmisartan, tetracyclines (eg, tetracycline)
Digoxin serum concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions and toxicity. Observe the clinical response of the patient and monitor digoxin serum concentrations. Adjust the digoxin dose as needed.
Aluminum salts (eg, aluminum hydroxide, kaolin-pectin, magaldrate), cholestyramine, colestipol, sucralfate
May decrease digoxin absorption, decreasing the efficacy. Administer digoxin at least 2 hours before the aluminum salt. Separate the administration times of digoxin and cholestyramine or colestipol by as much as possible. Separate the administration times of digoxin and sucralfate by at least 2 hours.
The positive inotropic effect of digoxin may be attenuated. If an interaction is suspected, discontinue one or both drugs. In addition, spironolactone may interfere with digoxin assay, resulting in falsely elevated levels.
Aminoglycosides, hydantoins (eg, phenytoin)
Digoxin pharmacologic effects may be increased or decreased. Observe the clinical response of the patient and monitor digoxin serum concentrations. Adjust the digoxin dose as needed.
Amphotericin B injectable–induced hypokalemia may increase the risk of digoxin toxicity.
Anticholinergics (eg, diphenoxylate, propantheline), metoclopramide
May increase digoxin absorption because of a decrease in GI motility. This interaction may be specific to the oral digoxin preparation and may be greater with slower dissolving tablets compared with digoxin elixir, or more recent tablet formulations.
Coadministration of digoxin and dofetilide has been associated with an increased rate of torsades de pointes.
Food, especially high-fiber meals, may decrease digoxin absorption.
Loop diuretics (eg, furosemide), thiazide diuretics (eg, chlorothiazide)
Drug-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias. Measure potassium and magnesium plasma concentrations and supplement low levels.
May cause sudden extrusion of potassium from muscle cells, resulting in arrhythmias in digitalized patients.
St. John’s wort
Digoxin serum concentrations may be reduced, decreasing the efficacy. Monitor digoxin concentrations and adjust the digoxin dose as needed.
Coadministration of sympathomimetics and digoxin may increase the risk of cardiac arrhythmias.
Thioamines (eg, methimazole, propylthiouracil)
Hyperthyroid patients may require a reduced dose of digoxin if they become euthyroid.
Digoxin toxicity has been reported during postmarketing experience.
Therapeutic Classification: antiarrhythmics, inotropics
Pharmacologic Classification: digitalis glycosides
Absorption: Tmax is 1 to 3 h (tablets), 30 to 90 min (oral solution). Food slows the rate of absorption after oral administration (tablets).
Bioavailability: 100% (IV), 70% to 85% (oral solution), 60% to 80% (tablets).
Distribution: 6 to 8 h tissue-distribution phase. Large apparent Vd. Crosses blood-brain barrier and placenta. Approximately 25% protein bound.
Metabolism: Approximately 16% metabolized; metabolites formed by hydrolysis, oxidation, and conjugation.
Excretion: Elimination follows first-order kinetics. 50% to 70% excreted unchanged in the urine (after IV administration). Half-life is 1.5 to 2 days.
Onset: 0.5 to 2 h (oral), 5 to 30 min (IV).
Peak: 2 to 6 h (oral), 1 to 4 h (IV).
Renal Function Impairment: Cl correlates with CrCl. Half-life is 3.5 to 5 days in anuric patients. Dosage adjustment recommended.
Hepatic Function Impairment: Plasma digoxin concentrations not affected by acute hepatitis.
Race: Pharmacokinetics not expected to be affected by race.
|ORALLY||30-120 MINUTE||2-8 HOUR||2-4 DAYS|
|INTRAMUSCULAR||30 MINUTE||4-6 HOUR||2-4 DAYS|
|INTRAVENOUS||5-30 MINUTE||1-4 HOUR||2-4 DAYS|
Duration listed is that for normal renal function; in impaired renal function, duration will be longer