Yes

Antiarrhythmic Agent, Class IV

Treatment of congestive heart failure, atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia, and cardiogenic shock

C

Hypersensitivity to digitoxin or any component (rare); digitalis toxicity; beriberi heart disease; A-V block; idiopathic hypertrophic subaortic stenosis; constrictive pericarditis; ventricular fibrillation; ventricular tachycardia

Use with caution in patients with hypoxia, hypothyroidism, or acute myocarditis. Do not use to treat obesity. Patients with incomplete A-V block (Stokes-Adams attack) may progress to complete block with digitalis drug administration. Use with caution in patients with acute myocardial infarction, severe pulmonary disease, idiopathic hypertrophic subaortic stenosis, Wolff-Parkinson-White syndrome, sick sinus syndrome (bradyarrhythmias), amyloid heart disease, and constrictive cardiomyopathies. Adjust dose with renal or hepatic impairment and aged patients. Elderly may develop exaggerated serum/tissue concentrations due to decreased lean body mass, total body water, and age-related reduction in renal/hepatic function. Exercise will reduce serum concentrations of digoxin due to increased skeletal muscle uptake.

1% to 10%: Gastrointestinal: Anorexia, nausea, vomiting

<1% (Limited to important or life-threatening symptoms): Sinus bradycardia, A-V block, S-A block, atrial or nodal ectopic beats, ventricular arrhythmias, bigeminy, trigeminy, atrial tachycardia with A-V block, drowsiness, headache, fatigue, lethargy, vertigo, disorientation, hyperkalemia with acute toxicity, feeding intolerance, abdominal pain, diarrhea, neuralgia, blurred vision, halos, yellow or green vision, diplopia, photophobia, flashing lights

Symptoms of acute overdose: Vomiting, hyperkalemia, sinus bradycardia, S-A arrest and A-V block are common, ventricular tachycardia, and fibrillation may occur

Chronic intoxication: Visual disturbances, weakness, sinus bradycardia, atrial fibrillation with slowed ventricular response, and ventricular arrhythmias

After GI decontamination, treat hyperkalemia if >5.5 mEq/L with sodium bicarbonate and glucose with insulin or Kayexalate®. Treat bradycardia or heart block with atropine or pacemaker and other arrhythmias with conventional antiarrhythmics. Use Digibind® for severe hyperkalemia, symptomatic arrhythmias unresponsive to other drugs, and for prophylactic treatment in massive overdose.

CYP3A3/4 enzyme substrate

Levothyroxine (and other thyroid supplements) may decrease digitoxin blood levels.

Enzyme inducers (phenytoin, phenobarbital, rifampin) may reduce the blood levels of digitoxin.

Amiloride may reduce the inotropic response to digitoxin.

Amiodarone reduces renal and nonrenal clearance of digitoxin and may have additive effects on heart rate.

Beta-blocking agents (propranolol) may have additive effects on heart rate.

Calcium preparations: Rare cases of acute digitalis glycoside toxicity have been associated with parental calcium (bolus) administration.

Moricizine may increase the toxicity of digitalis glycosides (mechanism undefined).

Propafenone increases digoxin blood levels. Effects may also occur with digitoxin. Monitor closely.

Propylthiouracil and methimazole may increase digitoxin blood levels by reducing thyroid hormone.

Quinidine increases digitoxin blood levels substantially; monitor blood levels/effect closely. Other related agents (hydroxychloroquine, quinine) should be used with caution.

Verapamil, diltiazem, bepridil, and nitrendipine increase digoxin concentrations, and may have similar effect on digitoxin. Other calcium channel blocking agents do not appear to share this effect.

Drugs which cause hypokalemia (thiazide and loop diuretics, amphotericin B): Hypokalemia may potentiate toxicity of digitalis glycosides.

These medications have been associated with reduced blood levels of digitalis glycosides which appear to be of limited clinical significance: Aminoglutethimide, antacids (magnesium- and aluminum-containing), sucralfate, sulfasalazine, ticlopidine.

These medications have been associated with increased digitalis glycoside blood levels which appear to be of limited clinical significance: Famciclovir, flecainide, ibuprofen, itraconazole, cimetidine, famotidine, fluoxetine, nefazodone, omeprazole, ranitidine, trimethoprim.

Digitalis binds to and inhibits magnesium and adenosine triphosphate dependent sodium and potassium ATPase thereby increasing the influx of calcium ions, from extracellular to intracellular cytoplasm due to the inhibition of sodium and potassium ion movement across the myocardial membranes; this increase in calcium ions results in a potentiation of the activity of the contractile heart muscle fibers and an increase in the force of myocardial contraction (positive inotropic effect); digitalis may also increase intracellular entry of calcium via slow calcium channel influx; stimulates release and blocks re-uptake of norepinephrine; decreases conduction through the S-A and A-V nodes

Absorption: 90% to 100%

Distribution: V_d: 7 L/kg

Protein binding: 90% to 97%

Metabolism: Hepatic, 50% to 70%

Time to peak: 8-12 hours

Half-life: 7-8 days

Elimination: 30% to 50% excreted unchanged in urine/feces

Oral:

<1 year: 0.045 mg/kg

1-2 years: 0.04 mg/kg

>2 years: 0.03 mg/kg which is equivalent to 0.75 mg/m²

Maintenance: Approximately 1/10 of the digitalizing dose

Adults: Oral:

Rapid loading dose: Initial: 0.6 mg followed by 0.4 mg and then 0.2 mg at intervals of 4-6 hours

Slow loading dose: 0.2 mg twice daily for a period of 4 days followed by a maintenance dose

Maintenance: 0.05-0.3 mg/day

Most common dose: 0.15 mg/day

Dosing adjustment in renal impairment: Cl_cr <10 mL/minute: Administer 50% to 75% of normal dose.

Hemodialysis: Not dialyzable (0% to 5%)

Dosing adjustment in hepatic impairment: Dosage reduction is necessary in severe liver disease.

Should be administered with water 30 minutes before or 2 hours after meals, with high-fiber foods and foods high in calcium; avoid natural licorice

Therapeutic: 20-35 ng/mL; Toxic: >45 ng/mL

Digoxin has a more established role in the treatment of heart failure and atrial fibrillation/flutter

Use vasoconstrictor with caution due to risk of cardiac arrhythmias with digitoxin

Sensitive gag reflex may cause difficulty in taking a dental impression

Do not discontinue medication without physician's advice; instruct patients to notify physician if they suffer loss of appetite, visual changes, nausea, vomiting, weakness, drowsiness, headache, confusion, or depression

Observe patients for noncardiac signs of toxicity: anorexia, vision changes (blurred), confusion, and depression

Tablet: 0.1 mg, 0.2 mg

Baciewicz AM, Isaacson ML, and Lipscomb GL, "Cholestyramine Resin in the Treatment of Digitoxin Toxicity," Drug Intell Clin Pharm, 1983, 17(1):57-9.

Hess T, Riesen W, Scholtysik G, et al, "Digitoxin Intoxication With Severe Thrombocytopenia: Reversal by Digoxin-Specific Antibodies," Eur J Clin Invest, 1983, 13(2):159-63.

Nolan PE and Mooradian AD, "Digoxin," Bressler R and Katz MD eds, Geriatric Pharmacology, New York, NY: McGraw-Hill, 1993, 7:151-63.

Park GD, Goldberg MJ, Spector R, et al, "The Effects of Activated Charcoal on Digoxin and Digitoxin Clearance," Drug Intell Clin Pharm, 1985, 19(12):937-41.

Taboulet P, Baud FJ, Bismuth C, et al, "Acute Digitalis Intoxication - Is Pacing Still Appropriate?" Clin Toxicol, 1993, 31:261-73.