Antiarrhythmic Agent, Class IV; Cardiac Glycoside
Treatment of congestive heart failure and to slow the ventricular rate in
tachyarrhythmias such as atrial fibrillation, atrial flutter, and
supraventricular tachycardia (paroxysmal atrial tachycardia); cardiogenic
Hypersensitivity to digoxin or any component; hypersensitivity to cardiac
glycosides (another may be tried); history of toxicity; ventricular tachycardia
or fibrillation; idiopathic hypertrophic subaortic stenosis; constrictive
pericarditis; amyloid disease; second- or third-degree heart block (except in
patients with a functioning artificial pacemaker); Wolff-Parkinson-White
syndrome and atrial fibrillation concurrently
Withdrawal in CHF patients may lead to recurrence of CHF symptoms. Some
arrhythmias that digoxin is used to treat may be exacerbated in digoxin
toxicity. Sinus nodal disease may be worsened. Adjust doses in renal impairment
and when verapamil, quinidine or amiodarone are added to a patient on digoxin.
Correct hypokalemia and hypomagnesemia before initiating therapy. Calcium,
especially when administered rapidly I.V., can produce serious arrhythmias.
Atrial arrhythmias associated with hypermetabolic states are very difficult to
treat. Rate control in atrial fibrillation may be better in a sedentary patient
than an active one. Use with caution in acute MI (within 6 months). Serum
concentration monitoring should be done before the next dose (patient can hold
AM dose for blood test) for an accurate assessment. Reduce or hold dose 1-2 days
before elective electrical cardioversion.
Incidence of reactions are not always reported.
Central nervous system: Visual disturbances (blurred or yellow vision),
headache (3.2%), weakness, dizziness (4.9%), apathy, confusion, mental
disturbances (4.1%), anxiety, depression, delirium, hallucinations, fever
Dermatologic: Maculopapular rash (1.6%), erythematous, scarlatiniform,
papular, vesicular or bullous rashes, urticaria, pruritus, facial, angioneurotic
or laryngeal edema, shedding of fingernails or toenails, alopecia
Gastrointestinal: Nausea (3.2%), vomiting (1.6%), diarrhea (3.2%), abdominal
<1% (Limited to important or life-threatening symptoms): Gynecomastia,
thrombocytopenia, palpitations, unifocal or multiform ventricular premature
contractions (especially bigeminy or trigeminy), anorexia, abdominal pain,
intestinal ischemia, hemorrhagic necrosis of the intestines, increase plasma
estrogen and decreased serum luteinizing hormone in men and postmenopausal women
and decreased plasma testosterone in men, vaginal cornification, eosinophilia,
sexual dysfunction, sweating
Children are more likely to experience cardiac arrhythmias as a sign of
excessive dosing. The most common are conduction disturbances or
tachyarrhythmias (atrial tachycardia with or without block) and junctional
tachycardia. Ventricular tachyarrhythmias are less common. In infants, sinus
bradycardia may be a sign of digoxin toxicity. Any arrhythmia seen in a child on
digoxin should be considered as digoxin toxicity. The gastrointestinal and
central nervous system symptoms are not frequently seen in children.
Symptoms of acute overdose: Vomiting, hyperkalemia, sinus bradycardia, S-A
arrest and A-V block are common, ventricular tachycardia, and fibrillation may
Chronic intoxication: Visual disturbances, weakness, sinus bradycardia,
atrial fibrillation with slowed ventricular response, and ventricular
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.
Amiloride may reduce the inotropic response to digoxin.
Cholestyramine, colestipol, kaolin-pectin may reduce digoxin absorption.
Levothyroxine (and other thyroid supplements) may decrease digoxin blood
Metoclopramide may reduce the absorption of digoxin tablets.
Penicillamine has been associated with reductions in digoxin blood levels
Amiodarone reduces renal and nonrenal clearance of digoxin and may have
additive effects on heart rate. Reduce digoxin dose by 50% with start of
Benzodiazepines (alprazolam, diazepam) have been associated with isolated
reports of digoxin toxicity.
Beta-blocking agents (propranolol) may have additive effects on heart rate.
Calcium preparations: Rare cases of acute digoxin toxicity have been
associated with parenteral calcium (bolus) administration.
Carvedilol may increase digoxin blood levels in addition to potentiating its
effects on heart rate.
Cyclosporine may increase digoxin levels, possibly due to reduced renal
Erythromycin, clarithromycin, and tetracyclines may increase digoxin (not
capsule form) blood levels in a subset of patients.
Indomethacin has been associated with isolated reports of increased digoxin
Itraconazole may increase digoxin blood levels in some patients; monitor.
Moricizine may increase the toxicity of digoxin (mechanism undefined).
Propafenone increases digoxin blood levels. Effects are highly variable;
Propylthiouracil (and methimazole) may increase digoxin blood levels by
reducing thyroid hormone.
Quinidine increases digoxin blood levels substantially. Effect is variable
(33% to 50%). Monitor digoxin blood levels/effect closely. Reduce digoxin dose
by 50% with start of quinidine. Other related agents (hydroxychloroquine,
quinine) should be used with caution.
Spironolactone may interfere with some digoxin assays, but may also increase
blood levels directly. However, spironolactone may attenuate the inotropic
effect of digoxin. Monitor effects of digoxin closely.
Succinylcholine administration to patients on digoxin has been associated
with an increased risk of arrhythmias.
Verapamil diltiazem, bepridil, and nitrendipine increased serum digoxin
concentrations. Other calcium channel blocking agents do not appear to share
this effect. Reduce digoxin's dose with the start of verapamil.
Drugs which cause hypokalemia (thiazide and loop diuretics, amphotericin B):
Hypokalemia may potentiate digoxin toxicity.
These medications have been associated with reduced digoxin blood levels
which appear to be of limited clinical significance: Aminoglutethimide,
aminosalicylic acid, aluminum-containing antacids, sucralfate, sulfasalazine,
These medications have been associated with increased digoxin blood levels
which appear to be of limited clinical significance: Famciclovir, flecainide,
ibuprofen, fluoxetine, nefazodone, cimetidine, famotidine, ranitidine,
Protect elixir and injection from light; solution compatibility:
D5W, D10W, NS, sterile water for injection (when diluted
fourfold or greater)
Congestive heart failure: Inhibition of the sodium/potassium ATPase pump
which acts to increase the intracellular sodium-calcium exchange to increase
intracellular calcium leading to increased contractility
Supraventricular arrhythmias: Direct suppression of the A-V node conduction
to increase effective refractory period and decrease conduction velocity -
positive inotropic effect, enhanced vagal tone, and decreased ventricular rate
to fast atrial arrhythmias. Atrial fibrillation may decrease sensitivity and
increase tolerance to higher serum digoxin concentrations.
Onset of action: Oral: 1-2 hours; I.V.: 5-30 minutes
Peak effect: Oral: 2-8 hours; I.V.: 1-4 hours
Duration: Adults: 3-4 days both forms
Absorption: By passive nonsaturable diffusion in the upper small intestine;
food may delay, but does not affect extent of digoxin absorption
Normal renal function: 6-7 L/kg
Vd: Extensive to peripheral tissues, with a distinct distribution
phase which lasts 6-8 hours; concentrates in heart, liver, kidney, skeletal
muscle and intestines. Heart/serum concentration is 70:1. Pharmacologic effects
are delayed and do not correlate well with serum concentrations during
Hyperthyroidism: Increased Vd
Hyperkalemia, hyponatremia: Decreased digoxin distribution to heart and
Hypokalemia: Increased digoxin distribution to heart and muscles
Concomitant quinidine therapy: Decreased Vd
Chronic renal failure: 4-6 L/kg
Decreased sodium/potassium ATPase activity - decreased tissue binding
Neonates, full term: 7.5-10 L/kg
Children: 16 L/kg
Adults: 7 L/kg, decreased with renal disease
Protein binding: 30% (in uremic patients, digoxin is displaced from plasma
protein binding sites)
Metabolism: By sequential sugar hydrolysis in the stomach or by reduction of
lactone ring by intestinal bacteria (in ~10% of population, gut bacteria may
metabolize up to 40% of digoxin dose); metabolites may contribute to therapeutic
and toxic effects of digoxin; metabolism is reduced in patients with CHF
Bioavailability: Oral (dependent upon formulation): Elixir: 75% to 85%;
Tablets: 70% to 80%
Half-life: Dependent upon age, renal and cardiac function:
Neonates: Premature: 61-170 hours; Full-term: 35-45 hours
Infants: 18-25 hours
Children: 35 hours
Adults: 38-48 hours
Adults, anephric: 4-6 days
Half-life: Parent drug: 38 hours; Metabolites: Digoxigenin: 4 hours;
Monodigitoxoside: 3-12 hours
Time to peak serum concentration: Oral: Within 1 hour
Elimination: 50% to 70% excreted unchanged in urine
When changing from oral (tablets or liquid) or I.M. to I.V. therapy, dosage
should be reduced by 20% to 25%. Refer to the following: Refer to the following:
Total digitalizing dose **: Oral: 20-30 mcg/kg*; I.V. or I.M.: 15-25
Daily maintenance dose***: Oral: 5-7.5 mcg/kg*; I.V. or I.M.: 4-6 mcg/kg*
I.V. or I.M.
Total digitalizing dose **: Oral: 25-35 mcg/kg*; I.V. or I.M.: 20-30 mcg/kg*
I.V. or I.M.
Daily maintenance dose***: Oral: 6-10 mcg/kg*; I.V. or I.M.: 5-8 mcg/kg* I.V.
1 month to 2 years*
Total digitalizing dose **: Oral: 35-60 mcg/kg*; I.V. or I.M.: 30-50 mcg/kg*
I.V. or I.M.
Daily maintenance dose***: Oral: 10-15 mcg/kg*; I.V. or I.M.: 7.5- 12
Total digitalizing dose **: Oral: 30-40 mcg/kg*; I.V. or I.M.: 25-35
Daily maintenance dose***: Oral: 7.5-10 mcg/kg*; I.V. or I.M.: 6-9
Total digitalizing dose **: Oral: 20-35 mcg/kg*; I.V. or I.M.: 15-30
Daily maintenance dose***: Oral: 5-10 mcg/kg*; I.V. or I.M.: 4-8 mcg/kg*
Total digitalizing dose **: Oral: 10-15 mcg/kg*; I.V. or I.M.: 8-12
Daily maintenance dose***: Oral: 2.5-5 mcg/kg*; I.V. or I.M.: 2-3 mcg/kg*
Total digitalizing dose **: Oral: 0.75-1.5 mg; I.V. or I.M.: 0.5-1 mg
Daily maintenance dose***: Oral: 0.125 mg- 0.5 mg; I.V. or I.M.: 0.1 mg- 0.4
*Based on lean body weight and normal renal function for age. Decrease dose
in patients with decreased renal function; digitalizing dose often not
recommended in infants and children.
**Give one-half of the total digitalizing dose (TDD) in the initial dose,
then give one-quarter of the TDD in each of two subsequent doses at 8- to
12-hour intervals. Obtain EKG 6 hours after each dose to assess potential
***Divided every 12 hours in infants and children <10 years of age; given
once daily to children >10 years of age and adults
Dosing adjustment/interval in renal impairment:
Clcr 10-50 mL/minute: Administer 25% to 75% of dose or every 36
Clcr <10 mL/minute: Administer 10% to 25% of dose or every 48
Reduce loading dose by 50% in ESRD
Hemodialysis: Not dialyzable (0% to 5%)
Meals containing increased fiber (bran) or foods high in pectin, may decrease
oral absorption of digoxin; avoid natural licorice (causes sodium and water
retention and increases potassium loss); maintain adequate amounts of potassium
in diet to decrease risk of hypokalemia (hypokalemia may increase risk of
When to draw serum digoxin concentrations: Digoxin serum concentrations are
monitored because digoxin possesses a narrow therapeutic serum range; the
therapeutic endpoint is difficult to quantify and digoxin toxicity may be
life-threatening. Digoxin serum levels should be drawn at least 4 hours
after an intravenous dose and at least 6 hours after an oral dose
(optimally 12-24 hours after a dose).
Initiation of therapy:
If a loading dose is given: Digoxin serum concentration may be drawn
within 12-24 hours after the initial loading dose administration. Levels drawn
this early may confirm the relationship of digoxin plasma levels and response
but are of little value in determining maintenance doses.
If a loading dose is not given: Digoxin serum concentration should be
obtained after 3-5 days of therapy
Trough concentrations should be followed just prior to the next dose
or at a minimum of 4 hours after an I.V. dose and at least 6 hours after an oral
Digoxin serum concentrations should be obtained within 5-7 days (approximate
time to steady-state) after any dosage changes. Continue to obtain digoxin serum
concentrations 7-14 days after any change in maintenance dose. Note: In
patients with end-stage renal disease, it may take 15-20 days to reach
Additionally, patients who are receiving potassium-depleting medications such
as diuretics, should be monitored for potassium, magnesium, and calcium levels
Digoxin serum concentrations should be obtained whenever any of the following
Questionable patient compliance or to evaluate clinical deterioration
following an initial good response
Changing renal function
Suspected digoxin toxicity
Initiation or discontinuation of therapy with drugs (amiodarone, quinidine,
verapamil) which potentially interact with digoxin; if quinidine therapy is
started; digoxin levels should be drawn within the first 24 hours after starting
quinidine therapy, then 7-14 days later or empirically skip one day's digoxin
dose and decrease the daily dose by 50%
Any disease changes (hypothyroidism)
Heart rate and rhythm should be monitored along with periodic EKGs to assess
both desired effects and signs of toxicity
Follow closely (especially in patients receiving diuretics or amphotericin)
for decreased serum potassium and magnesium or increased calcium, all of which
predispose to digoxin toxicity
Assess renal function
Be aware of drug interactions
Digoxin therapeutic serum concentrations:
Congestive heart failure: 0.8-2 ng/mL
Arrhythmias: 1.5-2.5 ng/mL
Adults: <0.5 ng/mL; probably indicates underdigitalization unless there
are special circumstances
Toxic: >2.5 ng/mL; tachyarrhythmias commonly require levels >2 ng/mL
Digoxin-like immunoreactive substance (DLIS) may cross-react with digoxin
immunoassay. DLIS has been found in patients with renal and liver disease,
congestive heart failure, neonates, and pregnant women (3rd trimester).
Digoxin has been used for many years in treatment of heart failure. Even
though digoxin has a very narrow therapeutic index, it remains an important
therapeutic strategy when added to standard therapy. When used in heart failure,
it should be used only for systolic dysfunction and not diastolic dysfunction.
While the long-term trials show no convincing reduction in cardiovascular
mortality, digoxin therapy is associated with a decrease in frequency in
hospitalizations for exacerbations of heart failure. A potential mechanism of
benefit in heart failure is that digoxin may improve baroreflex sensitivity.
Digoxin toxicity may be potentiated in patients with hypokalemia,
hypomagnesemia, and hypocalcemia. Digoxin may also rapidly approach toxic levels
in patients with renal failure. For patients with renal failure, the loading
dose is unchanged but maintenance doses may be adjusted and levels should be
monitored very carefully. Signs of digoxin toxicity include both brady- and
tachyarrhythmias. Bidirectional VT induced by digitalis toxicity indicates
imminent development of ventricular fibrillation. The recent development of
digoxin antibodies (Digibind®) allows rapid intervention
for acute digoxin toxicity. However, it is important to note that after
administration of Digibind®, measured digoxin levels
cannot be used to follow effectiveness of antibody therapy because they seem to
|Mental Health: Effects
on Mental Status|
May cause sedation
Effects on Psychiatric
Phenytoin may decrease levels of digoxin; monitor levels
|Dental Health: Local
Use vasoconstrictor with caution due to risk of cardiac arrhythmias with
Effects on Dental Treatment|
Sensitive gag reflex may cause difficulty in taking a dental
Take as directed; do not discontinue without consulting prescriber. Maintain
adequate dietary intake of potassium (do not increase without consulting
prescriber). Adequate dietary potassium will reduce risk of digoxin toxicity.
Take pulse at the same time each day; follow prescriber instructions for holding
medication if pulse is below 50. Notify prescriber of acute changes in pulse.
Report loss of appetite, nausea, vomiting, persistent diarrhea, swelling of
extremities, palpitations, "yellowing" or blurred vision, mental confusion or
depression, or unusual fatigue. Pregnancy precautions: Inform prescriber
if you are or intend to be pregnant.
Observe patients for noncardiac signs of toxicity, ie, anorexia, vision
changes (blurred), confusion, and depression
Capsule: 50 mcg, 100 mcg, 200 mcg
Elixir, pediatric (lime flavor): 50 mcg/mL with alcohol 10% (60 mL)
Injection: 250 mcg/mL (1 mL, 2 mL)
Injection, pediatric: 100 mcg/mL (1 mL)
Tablet: 125 mcg, 250 mcg, 500 mcg
Agency for Health Care Policy and Research, Clinical Practice Guidelines,
"Heart Failure: Evaluation and Care of Patients With Left-Ventricular Systolic Dysfunction,"
U.S. Department of Health and Human Services, Pub No 94-0612, June 1994.
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