digoxin (Rx)

1-10%

Dizziness (4.9%)

Mental disturbances (4.1%)

Diarrhea (3.2%)

Headache (3.2%)

Nausea (3.2%)

Vomiting (1.6%)

Maculopapular rash (1.6%)

<1%

Anorexia

Cardiac dysrhythmia

Arrhythmia in children (consider a toxicity)

Frequency Not Defined

Visual disturbance (blurred or yellow vision)

Heart block (1°/2°/3°)

Asystole

Tachycardia

Contraindications

Hypersensitivity

Ventricular fibrillation

Cautions

Use caution in chronic constrictive pericarditis, electrical cardioversion, severe bradycardia, severe heart failure, severe pulmonary disease, sick sinus syndrome, ventricular tachycardia, ventricular premature contractions, Wolff-Parkinson-White syndrome, electrolyte imbalance, hypothyroidism or hyperthyroidism, hypoxia, idiopathic hypertrophic subaortic stenosis, renal disease, concomitant diuretics

Not recommended in patients with acute myocardial infarction

Avoid in patients with myocarditis

Risk of advanced or complete heart block in patients with sinus node disease and AV block

Very narrow margin between effective therapeutic and toxic dosages: Therapeutic range, 0.5-2 ng/mL (target 0.5-1 ng/mL); toxic range, >2.5 ng/mL 

Generally avoid if left ventricular systolic function preserved, although may be used for ventricular rate control in subgroup with chronic atrial fibrillation

Less effective in presence of hypokalemia or hypocalcemia; avoid hypercalcemia or hypomagnesemia, which may predispose to serious arrhythmias

Heart failure patients with preserved ventricular function, including acute cor pulmonale, amyloid heart disease, and constrictive pericarditis may be susceptible to digoxin toxicity

May cause false-positive ST-T changes during exercise testing

Do not switch between different PO forms or between brand and generic forms of digoxin; bioavailability varies

Serum levels drawn within 6-8 hours of dose will be falsely high because of prolonged distribution phase

Increased risk of estrogen-like effects in geriatric patients

Beriberi heart disease may not respond adequately if underlying thiamine deficiency not corrected

Atrial arrhythmias are difficult to treat if associated with hypermetabolic (hyperthyroidism) or hyperdynamic (hypoxia) states; treat underlying condition before initiating therapy

Avoid extravasation; ensure proper needle or catheter placement prior to and during administration

Monitor for proarrhythmic effects, especially with digoxin toxicity

Use caution in patients with acute myocardial infarction; may increase myocardial oxygen demand; during acute coronary syndrome, digoxin administered IV may be used to slow a rapid ventricular response and improve left ventricular function in the acute treatment of atrial fibrillation associated with severe LV function and heart failure or hemodynamic instability

Monitor serum concentration closely when used for rate control in patients with atrial fibrillation; serum concentration that is not properly controlled are associated with increased risk of mortality

Consider use of digoxin only in heart failure with reduced ejection fraction when symptoms remain despite guideline-directed medical therapy; withdrawal of digoxin in clinically stable patients with heart failure may lead to recurrence of heart failure symptoms

In hypertrophic cardiomyopathy, outflow obstruction may worsen due to positive inotropic effects of digoxin; avoid use unless used to control ventricular response with atrial fibrillation; in the absence of atrial fibrillation, digoxin is potentially harmful in the treatment of dyspnea in patients with hypertrophic cardiomyopathy

Avoid rapid IV administration in digitalized patients; may produce serious arrhythmias

Not necessary to routinely reduce or hold digoxin therapy prior to elective electrical cardioversion for atrial fibrillation; however, exclusion of digoxin toxicity is necessary prior to cardioversion; whithold digoxin and delay cardioversion until toxicity subsides if signs of digoxin excess exist

Mechanism of Action

Digoxin inhibits Na-K ATPase, which in turn causes increased availability of intracellular calcium in the myocardium and conduction system. Inotropy and automaticity are subsequently increased while conduction velocity is reduced. Therapy indirectly causes parasympathetic stimulation of autonomic nervous system, with consequent effects on the sino-atrial (SA) and atrioventricular (AV) nodes.

Digoxin reduces catecholamine reuptake at nerve terminals, rendering blood vessels more sensitive to endogenous or exogenous catecholamines. Increases baroreceptor sensitization, with consequent increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increment in mean arterial pressure. At higher concentration, increases sympathetic outflow from the central nervous system (CNS) to both cardiac and peripheral sympathetic nerves. It also allows progressive efflux of intracellular potassium, with consequent increase in serum potassium levels.

Absorption

Bioavailability: 60-80 % (tablet); 70-85% (elixir)

Onset: 0.5-2 hr (PO) for initial effect and 2-6 hr for maximal effect; 5-30 min (IV) for initial effect and 1.5-4 hr for maximal effect 

Duration: 3-4 days 

Peak serum time: 1-3 hr (PO) 

Distribution

Protein bound: 20-25% 

Vd: 6-7 L/kg 

Metabolism

Metabolized by liver 

Metabolites: Digoxigenin bisdigitoxoside, digoxigenin monodigitoxoside (active) 

Elimination

Half-life: 1-3 days

Excretion: Urine (57-80%), feces (9-13%; includes bile)

IV Compatibilities

Solution: D5/½NS with potassium chloride 20 mEq, D5W, LR, ½NS, NS

Additive: Bretylium, cimetidine, floxacillin, furosemide, lidocaine, ranitidine, verapamil

Syringe: Heparin, milrinone

Y-site: Bivalirudin, ciprofloxacin, cisatracurium, dexmedetomidine, diltiazem, famotidine, fenoldopam, gatifloxacin, heparin with hydrocortisone, Hextend, inamrinone, linezolid, meperidine, meropenem, midazolam, milrinone, morphine sulfate, potassium chloride, remifentanil, tacrolimus, vitamins B and C

IV Incompatibilities

Additive: Dobutamine

Syringe: Doxapram

Y-site: Amphotericin B cholesteryl sulfate, amiodarone, fluconazole, foscarnet, insulin (beef, pork, and Humulin R[?]), propofol

IV Preparation

Dilute with 4-fold or greater volume of SWI, D5W, or NS

IV Administration

Administer slowly by direct IV injection over minimum of 5 minutes (longer if given undiluted)

Do not administer if precipitate present

Drug is severe skin irritant when given IV/IM and may cause severe local skin reaction with possible sloughing 

Storage

Store at controlled room temperature

Protect from light