Digoxin is an inotropic and antiarrhythmic drug that belongs to the class of cardiac glycosides. Atrial fibrillation, atrial flutter, and heart failure can all be treated with digoxin. Moreover, it is utilised to treat foetal supraventricular tachyarrhythmia and supraventricular tachycardia.

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September 3, 2022
Digoxin
medicaldialogues.in/generics/digoxin-2721723
Indications, Uses, Dosage, Drugs Interactions, Side effects
Digoxin
Medicine Type :
Allopathy
Prescription Type:
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Pharmacological Class:
Cardiac Glycosides,
Therapy Class:
Antiarrhythmic/ Inotropic drug,
Digoxin is an antiarrhytmic agent / inotropic agent belonging to Cardiac Glycosides class.
Digoxin is approved for the treatment of Heart failure, Atrial fibrillation and atrial flutter.
It is also used in treatment of Supraventricular tachycardia and fetal supraventricular
tachyarrhythmia.

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Digoxin absorption from gastrointestinal tract is variable with bioavailability of 63% (as
tablet) and 75% (as oral solution). It is widely distributed in tissues which crosses the
placenta and enters the breast milk. The volume of distribution was found to be 7 L/kg
with plasma protein binding of Approx 25%. It gets metabolised to active and inactive
metabolites, mainly di-hydrodigoxin and digoxygenin. It gets excreted via urine (50-70%
as unchanged drug) with elimination half-life of 36-48 hours.
The common side effects associated with Digoxin include headache, sedation,
Gynecomastia, hypotension, dizziness, asthenia, bradycardia, dry mouth, vomiting,
fatigue and upper abdominal pain, etc.
Digoxin is available in the dosage forms such as tablets ,oral solution and injections.
Digoxin is available in India, Italy, USA, Switzerland.
Digoxin, belonging to cardiac glycoside class, acts as a Antiarrhythmic agent. Digoxin
works by affecting the certain minerals (sodium and potassium) inside heart cells. This
decreases strain on the heart and helps to maintain a normal, steady, and strong
heartbeat..
Digoxin has two principle mechanisms of action which are selectively employed
depending on the indication:
Positive Ionotropic and AV Node Inhibition.
In Positive Ionotropic it increases the force of contraction of the heart by reversibly
inhibiting the activity of the myocardial Na-K ATPase pump.
While in AV node Inhibition Digoxin has vagomimetic effects on the AV node. By
stimulating the parasympathetic nervous system, it slows electrical conduction in
the atrioventricular node, therefore, decreases the heart rate.
The onset of action of Digoxin occurs within 1-2 hours for oral and 5-60 minutes for IV.
The Duration of Action for Digoxin within 3-4 days.
The Tmax was found within 2-6 hous and Cmax in blood reached upto 1.32 ± 0.18 ng/ml
.
Digoxin is available in the form of tablets, oral solution and Injections.
For Tablets and Oral Solution:
Digoxin tablets and oral solution should be taken orally by mouth with or without water.
For Injection:
Each dose should be given by the intravenous infusion over 10 - 20 minutes. The total
loading dose should be administered in the divided doses with approximately half of the
total dose given as the first dose and further fractions of the total dose given at intervals of
-
1

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4 - 8 hours.
Digoxin is approved for the treatment of Heart failure and Atrial fibrillation and atrial flutter. It is also
used in the treatment of Supraventricular tachycardia and fetal supraventricular tachyarrhythmia.
The main mechanism of action of digitalis is on the sodium-potassium ATPase of cardiac
myocyte. It reversibly inhibits the ATPase resulting in increased intracellular sodium
levels. The build-up of intracellular sodium leads to a shift of sodium extracellularly
through another channel in the exchange for calcium ions. This influx of intracellular
calcium assists with the myocyte contractility. Digoxin also has the direct effects on the
conduction through increased vagal tone. Digoxin stimulates the vagus nerve leading to
prolonged conduction through the sinoatrial (SA) and atrioventricular (AV) nodes.
Digoxin is approved for use in the following clinical indications:
Heart Failure
Digoxin is indicated for the treatment of mild to moderate heart failure in adults. Digoxin
increases the left ventricular ejection fraction and improves heart failure symptoms as
evidenced by improved exercise capacity and decreased heart failure-related
hospitalizations and emergency care, while having no effect on mortality. Where possible,
Digoxin should be used in combination with a diuretic and an angiotensin-converting
enzyme (ACE) inhibitor.
Digoxin increases myocardial contractility in pediatric patients with heart failure.
Atrial Fibrillation
Digoxin is indicated for the control of ventricular response rate in adult patients with
chronic atrial fibrillation.
Although not approved there have been certain off label uses documented for Digoxin:
Supraventricular tachycardias that are not controlled by traditional therapies may
benefit from digoxin.
Digoxin use has shown some success in the treatment of fetal supraventricular
tachyarrhythmia. The lowest effective dose should be administered to the mother as
digoxin might cause uterine contractions and result in abortion.
The dosage and the duration of treatment should be as per the clinical judgment of the
treating physician.
Digoxin is available in various dosage strength : 0.05 mg/ml; 0.1 mg/ml, 0.25 mg/ ml;
0.0625 mg, 0.125 mg, 0.1875 mg, 0.25 mg.
Digoxin is available in the form of tablets, oral solution and injections.
Digoxin should be used for the treatment of essential or primary Heart Failure.

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Heart Failure: In this, the limit of water and salt intake was suggested and It has
been observed that the low-salt Dietary Approaches to Stop Hypertension (DASH)
diet lowers blood pressure. Sometimes after a few weeks, its effects on blood
pressure become noticeable.
Atrial Fibrillation: Some foods can negatively affect your heart health and have
been shown to increase the risk of heart complications, like Atrial fibrillation as well
as heart disease. Diets high in processed foods, such as fast food, and items high in
added sugar, like soda and sugary baked goods, have been linked to increased heart
disease risk. They can also lead to other negative health outcomes like weight gain,
diabetes, cognitive decline, and certain cancers.
The dietary restriction should be individualized as per the patient requirements.
Digoxin may be contraindicated in the following
Acute myocardial infarction
Hypersensitivity to the drug
Ventricular fibrillation
Myocarditis
Hypomagnesemia
Hypokalemia
Wolf-Parkinson-White syndrome
Its use requires caution in cases of:
Hypercalcemia/hypocalcemia
Renal impairment
Diseased SA node
Bradycardia
AV block
Restrictive cardiomyopathy
Constrictive pericarditis
Thyroid disease - hypothyroidism leads to delayed drug clearance, and
hyperthyroidism does the opposite.
The treating physician must closely monitor the patient and keep pharmacovigilance as
follows
Use in Patients with the Accessory AV Pathway (Wolff-Parkinson-White
Syndrome)
Patients with Wolff-Parkinson-White syndrome who develop atrial fibrillation are at high
risk of ventricular fibrillation. Treatment of these patients with digoxin leads to greater
slowing of conduction in the atrioventricular node than in accessory pathways, and the
risks of rapid ventricular response leading to ventricular fibrillation are thereby increased.

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Use in Patients with Sinus Node Disease and AV Block
Because digoxin slows sinoatrial and AV conduction, the drug commonly prolongs the PR
interval. Digoxin may cause severe sinus bradycardia or sinoatrial block particularly in
patients with pre-existing sinus node disease and may cause advanced or complete heart
block in patients with pre-existing incomplete AV block. In such patients consideration
should be given to the insertion of a pacemaker before treatment with digoxin.
Misidentification of Digoxin Toxicity
Some signs and symptoms (anorexia, nausea, vomiting, and certain arrhythmias) can
equally result from digoxin toxicity as from congestive heart failure. Misidentification of
their etiology might lead the clinician to continue or increase digoxin dosing, when dosing
should actually be suspended. When the etiology of these signs and symptoms is not
obvious, measurement of serum digoxin levels may be helpful.
Use in Patients with Preserved Left Ventricular Systolic Function
Patients with certain disorders involving heart failure associated with preserved left
ventricular ejection fraction may not benefit from digoxin treatment and may be
particularly susceptible to adverse reactions when they are treated with digoxin.
In patients with hypertrophic cardiomyopathy (formerly called idiopathic hypertrophic
subaortic stenosis), the positive inotropic effect of digoxin leads to an increased
subvalvular outflow gradient and therefore, may compromise cardiac output. Digoxin is
rarely beneficial in patients with this condition. Chronic constrictive pericarditis is not
generally associated with any inotropic defect, so heart failure of this etiology is unlikely
to respond to treatment with digoxin. By slowing the resting heart rate, digoxin may
actually decrease cardiac output in these patients. Digoxin as an inotropic agent is of
limited value in patients with restrictive cardiomyopathies, although it has been used for
ventricular rate control in the subgroup of patients with atrial fibrillation. In addition,
patients with amyloid heart disease may be more susceptible to toxicity from digoxin at
therapeutic levels because of an increased binding of digoxin to extracellular amyloid
fibrils.
Use in Patients with Impaired Renal Function
Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal
function require smaller than usual maintenance doses of digoxin. Because of the
prolonged elimination half-life, a longer period of time is required to achieve an initial or
new steady-state serum concentration in patients with renal impairment than in patients
with normal renal function. If appropriate care is not taken to reduce the dose of digoxin,
such patients are at high risk for toxicity, and toxic effects will last longer in such patients
than in patients with normal renal function.
Use in Patients with Electrolyte Disorders

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In patients with hypokalemia or hypomagnesemia, toxicity may occur at concentrations
within therapeutic range because potassium or magnesium depletion sensitizes the
myocardium to digoxin. Therefore, it is desirable to maintain normal serum potassium
and magnesium concentrations in patients being treated with digoxin. Serum potassium
levels should be carefully monitored when digoxin is given to patients at high risk of
hypokalemia (e.g., those receiving diuretics, corticosteroids, or other drugs that
commonly lead to potassium loss; those with gastrointestinal losses through diarrhea,
vomiting, or nasogastric suction; or those with potassium-losing endocrinopathies or
nephropathies).
Digoxin toxicity is also more likely in the presence of hypomagnesemia. Hypomagnesemia
is common in most of the same conditions in which hypokalemia appears. Most notably, it
is commonly seen in alcoholics and in patients with diabetes mellitus or hypercalcemia.
Because digoxin’s therapeutic and toxic effects are all largely mediated by intracellular
calcium distribution, they are affected by abnormalities in serum calcium levels.
Hypercalcemia increases the risk of digoxin toxicity, while digoxin may be therapeutically
ineffective in the presence of hypocalcemia.
Use During Electrical Cardioversion
Reduction of digoxin dosage may be desirable prior to electrical cardioversion to avoid
induction of ventricular arrhythmias, but the physician must consider the consequences
of a rapid increase in ventricular response to atrial fibrillation if digoxin is with held 1 to 2
days prior to cardioversion. If there is a suspicion that digitalis toxicity exists, elective
cardioversion should be delayed. If it is not prudent to delay cardioversion, the energy
level selected should be minimal at first and carefully increased in an attempt to avoid
precipitating ventricular arrhythmias.
Use in Thyroid Disorders and Hypermetabolic States
Hypothyrodism may reduce the requirements for digoxin. Heart failure and atrial
arrhythmias resulting from hypermetabolic or hyperdynamic states (e.g.,
hyperthyroidism, hypoxia, or arteriovenous shunt) are best treated by addressing the
underlying condition. Atrial arrhythmias associated with hypermetabolic states (e.g.,
hyperthyroidism) are particularly resistant to digoxin treatment. Large doses of digoxin
are not recommended as the only treatment of these arrhythmias and care must be taken
to avoid toxicity if large doses of digoxin are required. In hypothyroidism, the digoxin
requirements are reduced. Digoxin responses are normal in patients with compensated
thyroid disease.
Use in Patients with Acute Myocardial Infarction
In patients with acute myocardial infarction, particularly if they have ongoing ischemia,
the use of inotropic drugs, such as digoxin, may result in undesirable increases in
myocardial oxygen demand and ischemia. Moreover, the use of digoxin may result in
potentially detrimental increases in coronary vascular resistance mediated through alpha

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adrenergic receptor stimulation. Use in Patients with Myocarditis Digoxin can precipitate
vasoconstriction and may promote production of pro-inflammatory cytokines. Therefore,
avoid digoxin in patients with myocarditis.
ECG Changes During Exercise
The use of therapeutic doses of digoxin may cause prolongation of the PR interval and
depression of the ST segment on the electrocardiogram. Digoxin may produce false
positive ST changes on the electrocardiogram during exercise testing that may be
indistinguishable from those of ischemia. These electrophysiologic effects reflect an
expected effect of the drug and are not indicative of toxicity. Digoxin does not significantly
decrease heart rate during exercise.
Alcohol Warning
Consumption of alcohol is not recommended while receiving this medicine as it may
increase the risk of adverse effects and lowers the blood pressure.
Breast Feeding Warning
Digoxin levels in human milk are lower than those in maternal serum. The estimated
exposure that a nursing infant would be expected to receive via breastfeeding would be far
below the usual infant maintenance dose. Therefore, this amount should have no
pharmacologic effect upon the infant. Nevertheless, caution should be exercised when
digoxin is administered to a nursing woman.
Pregnancy Warning
Teratogenic Effects (Pregnancy Category C)
Animal reproduction studies have not been conducted with digoxin. It is also not known
whether digoxin can cause fetal harm when administered to pregnant women or can affect
reproductive capacity. Digoxin should be given to a pregnant woman only if clearly
needed.
Food Warning
Banana: Avoid eating banana when you are on digoxin as it increases the
potassium level in the body. Excess potassium can lead to the heart failure or
irregular heartbeat.
Fiber Rich Foods: Foods rich in the fiber like wheat bran muffins and psyllium
interact with digoxin and reduce the absorption of digoxin from the digestive tract.
So take digoxin 1 hour before or 2 hours after eating foods that are rich in fiber.
Salt Substitutes: Digoxin interacts with foods that contain salt substitutes, where
potassium is replaced by sodium. Due to this interaction, the effectiveness of
digoxin in treating heart failure may be decreased.

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Senna and St.John's Wort:Digoxin interacts with both Senna and St. John's
wort, which lead to a reduction in the amount and activity of digoxin in the body.
Black Licorice with Glycyrrhizin:When you are on digoxin, avoid black licorice
in your diet as it may result in irregular heartbeat and heart attack.
Hawthorn Berry and Siberian Ginseng:These herbs interact with digoxin and
increase the activity of digoxin in the body.
The adverse reactions related to molecule Digoxin can be categorized as
Common Adverse effects:
Hemodynamic compromise, Dizziness, peripherial ischemia, dry mouth, asthenia and
somnolence.
Less Common adverse effects:
Asymptomatic and symptomatic hypotension, burning, crawling, itching, numbness.
Rare adverse effects:
Bradycardia, decompensated heart failure, cardiac arrest, and heart block.
The clinically relevant drug interactions of Digoxin is briefly summarized here.
Drug which increases digoxin level:
ACE inhibitors (e.g. captopril), angiotensin receptor blockers (e.g. telmisartan),
NSAIDs (e.g. indomethacin), COX-2 inhibitors, calcium channel blockers (e.g.
verapamil, felodipine, tinapamil), antiarrhythmics (e.g. amiodarone, flecainide)
antibiotics (e.g. erythromycin, tetracyclines), vasopressin receptor antagonist
(tolvaptan, conivaptan), itraconazole, quinine, alprazolam, propantheline,
nefazodone, atorvastatin, ciclosporin, epoprostenol, ritonavir, telaprevir,
ranolazine, lapatinib, ticagrelor may increase digoxin levels.
Drug which decreases digoxin levels:
Antacids, bulk-laxatives, kaolin-pectin, acarbose, neomycin, penicillamine,
rifampicin, some cytostatics, metoclopramide, sulfasalazine, adrenaline,
salbutamol, cholestyramine, phenytoin, St. John's wort, bupropion, and
supplemental enteral nutrient may decrease digoxin levels.
Pediatric Use
Digoxin increases myocardial contractility in pediatric patients with congestive
heart failure. There are no clinical efficacy studies demonstrating benefit in
pediatric patients with heart failure. There are no controlled randomized studies of
digoxin in pediatric patients with atrial tachyarrhythmias.
Geriatic Use

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The majority of the clinical experience increased with digoxin has been in the elderly
population. This experience has not identified differences in response or adverse effects
between the elderly and younger patients. However, this drug is known to be substantially
excreted by the kidney, and the risk of toxic reactions to this drug may be greater in
patients with impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection, which should be based
on renal function, and it may be useful to monitor renal function
Symptoms:
Gastrointestinal effects are often the first sign of toxicity which include anorexia, nausea,
vomiting, diarrhoea, abdominal pain, and bloating.
Cardiac manifestations including palpitations, syncope, multiple rhythm disturbance,
prolongation of the PR interval, AV conduction disturbance or sinus bradycardia, and
ventricular arrhythmias.
Neurologic and visual effects (e.g. dizziness, fatigue, malaise, weakness, drowsiness,
behavioural disturbance, and aberration of colour vision) may also occur.
Management:
Gastric lavage is rarely performed, consider pre-treatment with atropine.
In acute poisoning, large doses of activated charcoal prevent further absorption of digoxin
and decrease serum levels by intestinal binding of digoxin.
If hypokalaemia is present, oral or IV K supplements are given. Digoxin-specific antibody
Fab is a specific treatment for digoxin toxicity and is very effective.
Pharmacodynamics:
Digoxin is a positive inotropic and negative chronotropic drug, meaning that it increases
the force of the heartbeat and decreases the heart rate. The reduce in heart rate is
particularly useful in cases of atrial fibrillation, a condition characterized by a fast and
irregular heartbeat. The relief of heart failure symptoms during digoxin therapy has been
demonstrated in clinical studies by increased exercise capacity and reduced
hospitalization due to heart failure and reduced heart failure-related emergency medical
visits. Digoxin has a narrow therapeutic window. Digoxin poses a risk of rapid ventricular
response that can cause ventricular fibrillation in patients with an accessory
atrioventricular (AV) pathway. Cardiac arrest as a result of ventricular fibrillation is fatal.
An increased risk of fatal severe or complete heart block is present in individuals with pre-
existing sinus node disease and AV block who take digoxin.
Pharmacokinetics :
Absorption

10. 10/11
Digoxin is approximately 70-80% absorbed in the first part of the small bowel. The
bioavailability of an oral dose varies from 50-90%, however, oral gelatinized capsules of
digoxin are reported to have a bioavailability of 100%. Tmax, or the time to reach the
maximum concentration of digoxin was measured to be 1.0 h in one clinical study of
healthy patients taking 0.25 mg of digoxin with a placebo. Cmax, or maximum
concentration, was 1.32 ± 0.18 ng/ml−1 in the same study, and AUC (area under the
curve) was 12.5 ± 2.38 ng/ml−1. If digoxin is ingested after a meal, absorption is slowed
but this does not change the total amount of absorbed drug. If digoxin is taken with meals
that are in fiber, absorption may be decreased. Patients with malabsorption due to a
variety of causes may have a reduced ability to absorb digoxin. P-glycoprotein, located on
cells in the intestine, may interfere with digoxin pharmacokinetics, as it is a substrate of
this efflux transporter. P-glycoprotein can be induced by other drugs, therefore reducing
the effects of digoxin by increasing its efflux in the intestine.
Distribution
Following drug administration, a 6- to 8-hour tissue distribution phase is observed. This
is followed by a much more gradual decline in the serum concentration of the drug, which
is dependent on the elimination of digoxin from the body. Clinical evidence indicates that
the early high serum concentrations do not reflect the concentration of digoxin at its sites
of action, but that with chronic use, the steady-state post-distribution serum
concentrations are in equilibrium with tissue concentrations and correlate with
pharmacologic effects. In individual patients, these post-distribution serum
concentrations may be useful in evaluating therapeutic and toxic effects.
Digoxin is concentrated in tissues and therefore has a large apparent volume of
distribution. Digoxin crosses both the blood-brain barrier and the placenta. At delivery,
the serum digoxin concentration in the newborn is similar to the serum concentration in
the mother. Approximately 25% of digoxin in the plasma is bound to protein. Serum
digoxin concentrations are not significantly altered by large changes in fat tissue weight,
so that its distribution space correlates with lean (i.e., ideal) body weight, not total body
weight.
Metabolism
Sixteen percent of digoxin is metabolized. The end metabolites include 3-β-digoxigenin,
3-keto-digoxigenin, and their glucuronide and sulfate conjugates. The metabolism of
digoxin is not dependent on cytochrome P450 system, and digoxin is not known to induce
or inhibit the cytochrome P-450 system.
Excretion
Elimination of digoxin is predominantly renal, although in adult volunteers about a
quarter of serum digoxin is eliminated through the intestine, excreted in bile or secreted
directly into the lumen by P-glycoprotein. Elimination of digoxin follows first order
kinetics. Following intravenous administration to healthy volunteers, 50% to 70% of a
digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is

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proportional to glomerular filtration rate. The serum half-life of digoxin in pediatric
patients is reported to be 18 to 36 hours, and in adults it is typically 36 to 48 hours. The
half-life in anuric patients is prolonged to 3.5 to 5 days. Digoxin is not effectively removed
from the body by dialysis, exchange transfusion, or cardiopulmonary bypass because most
of the drug is bound to tissue.
There are some clinical studies of the drug Digoxin mentioned below:
1. https://clinicaltrials.gov/ct2/show/NCT03783429
2. https://www.nejm.org/doi/full/10.1056/nejm199702203360801
3. Chan BS, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin
toxicity. Clinical toxicology. 2014 Sep 1;52(8):824-36.
4. Ziff OJ, Kotecha D. Digoxin: The good and the bad. Trends in Cardiovascular Medicine.
2016 Oct 1;26(7):585-95.
5. Abad-Santos F, Carcas AJ, Ibáñez C, Frías J. Digoxin level and clinical manifestations
as determinants in the diagnosis of digoxin toxicity. Therapeutic drug monitoring. 2000
Apr 1;22(2):163-8.
1. Eichhorn EJ, Gheorghiade M. Digoxin. Progress in cardiovascular diseases. 2002
Jan 1;44(4):251-66.doi: https://doi.org/10.1053/pcad.2002.31591
2. Ehle M, Patel C, Giugliano RP. Digoxin: clinical highlights: a review of digoxin and
its use in contemporary medicine. Critical pathways in cardiology. 2011 Jun
1;10(2):93-8.doi: 10.1097/HPC.0b013e318221e7dd
3. https://go.drugbank.com/drugs/DB00390
4. https://reference.medscape.com/drug/lanoxin-digoxin-342432
5. https://www.mims.com/india/drug/info/digoxin?type=full&mtype=generic
6. https://www.ncbi.nlm.nih.gov/books/NBK556025/#article-90909.s6
7. https://oxfordmedicaleducation.com/prescribing/digoxin-loading/
Parthika Patel
Parthika Patel has completed her Graduated B.Pharm from SSR
COLLEGE OF PHARMACY and done M.Pharm in Pharmaceutics. She
can be contacted at editorial@medicaldialogues.in. Contact no. 011-
43720751
Dr JUHI SINGLA
Dr JUHI SINGLA has completed her MBBS from Era’s Lucknow
Medical college and done MD pharmacology from SGT UNIVERSITY
Gurgaon. She can be contacted at editorial@medicaldialogues.in.
Contact no. 011-43720751