Digoxin

(di jox' in)

PCaution when used during lactation - Caution when used during pregnancy

Molecule Info

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Indication(s) & Dosage

Congestive heart failure - Digoxin is useful regardless of whether the failure is predominantly of the left or right ventricle, or involves both sides of the heart. It is particularly useful in heart failure resulting from chronic overload (hypertension, valvular lesions, atherosclerotic heart disease) in which the supply of energy is not impaired. Digoxin does not cause major benefit in situations in which the metabolic energy supply is compromised as in thyrotoxicosis, hypoxia, and severe thiamine deficiency.

Atrial fibrillation - Because Digoxin depresses conduction in the atrioventricular bundle, producing a slower ventricular beat, it is valuable in atrial fibrillation. It will frequently convert atrial flutter into fibrillation and, upon withdrawal of the drug, normal sinus rhythm may be restored.

Paroxysmal atrial tachycardia - Digoxin may relieve or prevent an attack, but its use in paroxysmal ventricular tachycardia is dangerous.

Heart failure

Adult: Rapid digitalisation: Loading dose of 0.75-1.5 mg during the first 24-hr period as a single dose or in divided doses every 6 hr for less urgent or greater risk cases. For mild heart failure: Loading dose may not be required, 250 mcg 1-2 times daily. For patients with normal renal function, steady-state plasma concentrations are usually achieved in about 7 days. Usual maintenance: 125-250 mcg daily but may range from 62.5-500 mcg daily. 

Child: Neonate <1.5 kg: Initial: 25 mcg/kg/day in 3 divided doses for 24 hr, then 4-6 mcg/kg/day in 1-2 divided doses; neonate 1.5-2.5 kg: Initial: 30 mcg/kg/day in 3 divided doses for 24 hr, then 4-6 mcg/kg/day in 1-2 divided doses; Neonate >2.5 kg and child 1 mth-2 yr: Initial: 45 mcg/kg/day in 3 divided doses for 24 hr, then 10 mcg/kg/day in 1-2 divided doses. 2-5 yr: Initial: 35 mcg/kg/day in 3 divided doses for 24 hr, then 10 mcg/kg/day in 1-2 divided doses. 5-10 yr: Initial: 25 mcg/kg/day (max: 750 mcg/day) in 3 divided doses for 24 hr, then 6 mcg/kg/day (max: 250 mcg/day) in 1-2 divided doses. 10-18 yr: Initial: 0.75-1.5 mg/day in 3 divided doses for 24 hr, then 62.5-750 mcg/day in 1-2 divided doses. Reduce doses if patient has been given cardiac glycoside in the preceding 2 wk. 

Elderly: Lower doses are given.

Renal impairment: Dosage reductions may be needed.

Oral
Supraventricular arrhythmias

Adult: Rapid digitalisation: Loading dose of 0.75-1.5 mg during the first 24-hr period as a single dose or in divided doses every 6 hr for less urgent or greater risk cases. For mild heart failure: Loading dose may not be required, 250 mcg 1-2 times daily. For patients with normal renal function, steady-state plasma concentrations are usually achieved in about 7 days. Usual maintenance: 125-250 mcg daily but may range from 62.5-500 mcg daily. 

Child: Neonate <1.5 kg: Initial: 25 mcg/kg/day in 3 divided doses for 24 hr, then 4-6 mcg/kg/day in 1-2 divided doses; neonate 1.5-2.5 kg: Initial: 30 mcg/kg/day in 3 divided doses for 24 hr, then 4-6 mcg/kg/day in 1-2 divided doses; Neonate >2.5 kg and child 1 mth-2 yr: Initial: 45 mcg/kg/day in 3 divided doses for 24 hr, then 10 mcg/kg/day in 1-2 divided doses. 2-5 yr: Initial: 35 mcg/kg/day in 3 divided doses for 24 hr, then 10 mcg/kg/day in 1-2 divided doses. 5-10 yr: Initial: 25 mcg/kg/day (max: 750 mcg/day) in 3 divided doses for 24 hr, then 6 mcg/kg/day (max: 250 mcg/day) in 1-2 divided doses. 10-18 yr: Initial: 0.75-1.5 mg/day in 3 divided doses for 24 hr, then 62.5-750 mcg/day in 1-2 divided doses. Reduce doses if patient has been given cardiac glycoside in the preceding 2 wk. 

Elderly: Lower doses are given.

Renal impairment: Dosage reductions may be needed.

Intravenous
Emergency heart failure

Adult: For patients who have not received cardiac glycosides in the previous 2 wk. 0.5-1 mg by IV infusion as a single dose over at least 2 hr or in divided doses with each dose given over 10-20 minutes. Maintenance dose is usually given orally. 

Renal impairment: Dosage reductions may be needed.

Reconstitution: Admin undiluted or diluted with a 4-fold or greater volume of Sterile Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection. 
Incompatibility: Using less than a 4-fold volume of diluent could lead to precipitation of the digoxin.

Administration May be taken with or without food.
Overdosage Symptoms: Hyperkalaemia, cardiac arrhythmias and heart block. Management: Treatment is symptomatic and supportive. Reduce absorption by gastric lavage if present within 30 min of ingestion. Do not induce vomiting or attempt passage of a gastric tube if presented >2 hr after ingestion or already has toxic manifestations, as this may induce an acute vagal episode and worsen digitalis-related arrhythmias. Activated charcoal is helpful in reducing drug absorption. Monitor serum potassium levels and keep potassium levels between 4.0-5.5 mmol/l. Digoxin-specific antibody fragments (FAB) is a specific antidote for digoxin and may be used to reverse potentially life-threatening ventricular arrhythmias due to digoxin overdosage. Haemodialysis is unlikely to be useful.
Contraindications

Digoxin is contraindicated in the following conditions:

- Intermittent complete heart block or second degree atrioventricular block - especially if there is a history of Stokes-Adams attacks.
- Ventricular tachycardia and ventricular fibrillation.
- Arrhythmias caused by cardiac glycoside intoxication.
- Supraventricular arrhythmias associated with an accessory atrioventricular pathway, as in the Wolff-Parkinson-White syndrome, unless the electrophysiological characteristics of the accessory pathway and any possible deleterious effect of digoxin on these characteristics have been evaluated. If an accessory pathway is known or suspected to be present and there is no history of previous supraventricular arrhythmias, Digoxin is similarly contra-indicated.
- Hypertrophic obstructive cardiomyopathy, unless there is concomitant atrial fibrillation and heart failure but even then, caution should be exercised if Digoxin is to be used.
- Hypersensitivity to digoxin, other digitalis glycosides, or any other constituent

Special Precautions

Cardiac dysrhythmias, hypokalaemia, hypertension, IHD, hypercalcaemia, hypomagnesaemia, electroconversion, chronic cor pulmonale, aortic valve disease, acute myocarditis, congestive cardiomyopathies, constrictive pericarditis, heart block, elderly, renal impairment, abnormalities in thyroid function; pregnancy. IV digoxin can only be given to patients who have not received cardiac glycosides in the preceding 2 wk.

Direct current cardioversion: The risk of provoking dangerous arrhythmias with direct current cardioversion is greatly increased in the presence of digitalis toxicity and is in
proportion to the cardioversion energy used.

For elective direct current cardioversion of a patient who is taking digoxin, the drug should be withheld for 1 – 2 days before cardioversion is performed. In emergencies, such as cardiac arrest, when attempting cardioversion the lowest effective energy should be applied.

Direct current cardioversion is inappropriate in the treatment of arrhythmias thought to be caused by cardiac glycosides. Many beneficial effects of digoxin on arrhythmias result from a degree of atrioventricular conduction blockade. However, when incomplete atrioventricular block already exists the effects of a rapid progression in the block should be anticipated. In complete heart block, the idioventricular escape rhythm may be suppressed. The administration of digoxin in the period immediately following myocardial infarction is not contra-indicated. However, the use of inotropic drugs in some patients in this setting may result in undesirable increases in myocardial oxygen demand and ischaemia, and some retrospective follow-up studies have suggested digoxin to be associated with an increase risk of death. The possibility of arrhythmias arising in patients who may by hypokalaemic after myocardial infarction and are likely to be cardiologically unstable must be borne in mind. The limitations imposed thereafter on direct current cardioversion must also be remembered.

Adverse Drug Reaction(s) Extra beats, anorexia, nausea and vomiting. Diarrhoea in elderly, confusion, dizziness, drowsiness, restlessness, nervousness, agitation and amnesia, visual disturbances, gynaecomastia, local irritation (IM/SC inj), rapid IV admin may lead to vasocostriction and transient hypertension.
Potentially Fatal: Cardiac arrhythmias in combination with heart block.
Drug Interactions Effectiveness reduced by phenytoin, neomycin, sulphasalazine, kaolin, pectin, antacids and in patients receiving radiotherapy. Metoclopramide may alter the absorption of solid dosage forms of digoxin. Blood levels increased bycalcium channel blockers, spironolactone, quinidine and calcium salts.
Potentially Fatal: Electrolyte imbalances such as hypokalaemia and hypomagnesemia (e.g. admin of potassium-losing diuretics, corticosteroids) can increase the risk of cardiac toxicity.
Food Interaction Absorption delayed.
Lab Interference May increase conc of urinary 17-hydroxycorticosteroids.
Pregnancy Category (FDA) and use in Specific Population

Pregnancy Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Labor and Delivery 

There is not enough data from clinical trials to determine the safety and efficacy of digoxin during labor and delivery.

Nursing Mothers

Studies have shown that digoxin distributes into breast milk, and that the milk-to-serum concentration ratio is approximately 0.6 to 0.9. However, the estimated exposure of a nursing infant to digoxin via breastfeeding is 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.

Pediatric Use

The safety and effectiveness of Digoxin in the control of ventricular rate in children with atrial fibrillation in children have not been established.

The safety and effectiveness of Digoxin in the treatment of heart failure in children have not been established in adequate and well-controlled studies. However, in published literature of children with heart failure due to various etiologies (e.g., ventricular septal defects, anthracycline toxicity, patent ductus arteriosus), treatment with digoxin has been associated with improvements in hemodynamic parameters, and in clinical signs and symptoms.

Newborn infants display considerable variability in their tolerance to digoxin. Premature and immature infants are particularly sensitive to the effects of digoxin, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity.

Geriatric Use

The majority of clinical experience gained 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.

Storage Store at 25°C.
Pharmacology

Mechanism of Actions: 

Digoxin is a cardiac glycoside with molecular haemodynamic, neurohumoral and electrophysiological effects contributing to its efficacy in heart failure.

Primary action of Digoxin is to reversibly inhibit the alpha subunit of sodium-potassium adenosine triphosphatase (ATPase). This result in inhibitors of sodium-potassium
exchange allowing calcium to accumulate in cardiac myocytes by augmenting calcium ion influx. This is responsible for the positive inotropic effect of digoxin or increase force of contraction. This action is more pronounced in decompensated heart failure with systolic dysfunction. Extracellular potassium promotes dephosphorylation of the ATPase and decreases the affinity of the enzyme for digoxin.

- Digoxin increases contractility without increasing ventricular rate.
- Digoxin increases the sensitivity of baroreceptors thereby leading to reduced sympathetic drive.
 - Digoxin increases parasympathetic tone. Increase in efferent vagal impulses results in reduced sympathetic tone and diminished impulse conduction rate through the atria and atrioventricular node. Thus a major beneficial effect of digoxin is reduction in ventricular rate. Digoxin prolongs the effective refractory period
- Digoxin decreases plasma renin activity and serum aldosterone levels. Reduced activation of the sympathetic nervous system and renin-angiotensin system appears to
be independent of its inotropic action in heart failure. The modulatory neurohumoral action appears to contribute significantly to the efficacy of digoxin.
- In patients with heart failure, digoxin decreases vascular resistance and venous tone as a consequence of altered autonomic activity.
- Digoxin indirectly improves renal function secondary to increase in renal perfusion resulting in diuresis.

At higher concentrations cardiac glycosides can increase sympathetic activity and directly affect automaticity.

Pharmacodynamics

The times to onset of pharmacologic effect and to peak effect of preparations of Digoxin are shown in Table 1.

Table 1: Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of Digoxin

PRODUCT TIME TO ONSET OF EFFECTA TIME TO PEAK EFFECTA
Digoxin Tablets 0.5 -2 hours 2 -6 hours
Digoxin Injection/IV 5 -30 minutes b 1 -4 hours
aDocumented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. 
bDepending upon rate of infusion.
Hemodynamic Effects

Short-and long-term therapy with the drug increase cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance in patients with heart failure. These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions.

ECG Changes

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-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects are not indicative of toxicity. Digoxin does not significantly reduce heart rate during exercise.

Digoxin is a cardiac glycoside which has positive inotropic activity characterized by an increase in the force of myocardial contraction. It also reduces the conductivity of the heart through the atrioventricular (AV) node. Digoxin also exerts direct action on vascular smooth muscle and indirect effects mediated primarily by the autonomic nervous system and an increase in vagal activity.
Absorption: Absorption from the GI tract is variable.
Distribution: Widely distributed in tissues, including the heart, brain, erythrocytes, and skeletal muscle. 20-30% bound to plasma proteins.
Excretion: Excreted mainly unchanged.

ATC Classification C01AA05 - digoxin; Belongs to the class of digitalis glycosides. Used in the treatment of heart failure.

 

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Brand/Product Info


Total Products : 4    
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
AGOXIN Aristopharma Ltd. Digoxin 0.25mg Tablet 100's: 109.00 MRP
CENTOXIN Opsonin Pharma Limited Digoxin 0.25mg Tablet 50's: 54.50 MRP
CENTOXIN Elixir Opsonin Pharma Limited Digoxin 0.25mg/5ml Syrup 60ml: 75.00 MRP
DIGOXEN Drug International Ltd Digoxin USP 0.1mg & 0.2mg Soft Capsule 0.1 mg x 100's, 0.2mg x 50's: 94.00 & 67.00 MRP

Gen. MedInfo

Why this medicine is required?

Digoxin is used to treat heart failure and certain types of heart disease in which the heart rhythm is irregular, such as atrial fibrillation and atrial flutter.

Digoxin works by giving better control over your heart rate and rhythm. It also improves the contraction power of your heart.

How to take this medicine?

Take Digoxin exactly as directed by your doctor. Do not take more or less than instructed by your doctor. 

Digoxin must be taken regularly for it to be effective. Continue taking it even when you feel better. Do not stop taking it unless instructed by your doctor. Your condition may worsen if Digoxin is stopped suddenly.

You may take Digoxin with or without food. Try to take it at the same time each day.

Do not take Digoxin together with high fibre foods such as cereals, high fibre bread, fruit or vegetables as these can reduce the absorption of Digoxin.

Do not switch between different brands of Digoxin unless your doctor has specifically told you to do so.

What should be done if I have forgotten to take this medicine?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and return to your normal schedule.

DO NOT double a dose under any circumstances.

Remember to take your medicine regularly. Digoxin must be taken exactly as directed for it to be effective. If you often forget to take your medicine, let your doctor know.

When not to use this medicine?

Digoxin may not be suitable for certain heart conditions. Alert your doctor to any heart conditions that you have.

Before using this medicine.

Alert your doctor if you have any of these conditions or any other illnesses:

- a recent heart attack
- low levels of potassium or magnesium in the blood
- high levels of calcium in the blood
- a heart problem known as "Beri-Beri disease"
- kidney or liver disease
- lung disease
- thyroid problems
- digestive problems or other bowel problems

Inform your doctor if you are pregnant or breastfeeding.

Why is it important to keep my appointments with the doctor?

Your doctor needs to check your response to Digoxin regularly. He may also need to do routine blood tests and an electrocardiogram (ECG) to monitor your condition. Be sure to keep all appointments with your doctor.

What side effects could appear?

Digoxin may cause drowsiness and dizziness. If you feel drowsy or dizzy, do not drive or take part in any activity in which you need to be alert.

Digoxin may also cause slow, irregular or pounding heartbeat, nausea, vomiting, diarrhoea, loss of appetite, confusion and rash. Digoxin may also cause changes in your vision such as blurred vision or yellow-coloured vision. Alert your doctor if these side effects are severe or refuse to go away.

Other side effects are less common but may need immediate medical attention. Alert your doctor if you develop any of these symptoms:

- chest pain
- difficulty breathing
- profuse sweating with an abnormally fast or irregular heartbeat

Can this be taken with other medicines?

Alert your doctor if you are taking any other medicines, especially those listed here:

- other medicines for heart problems, irregular heart beat or high blood pressure especially amiodarone, dronedarone, propafenone, quinidine, midodrine, verapamil, felodipine, tiapamil
- diuretics ("water pills") such as frusemide, furosemide, bumetanide, hydrochlorothiazide, spironolactone
- asthma medicines
- mood medicines such as nefazodone, trazodone, diazepam, alprazolam
- cholesterol medicines
- immunosuppressants
- epilepsy (fits) medicines
- cancer medicines
- laxatives
- painkillers such as indomethacin
- medicines for anaesthesia such as succinylcholine
- medicines for stomach problems such diphenoxylate, metoclopramide or propantheline
- antibiotics such as erythromycin, clarithromycin, ciprofloxacin and related medicines
- antifungal medicines such as itraconazole, amphotericin B
- tuberculosis (TB) medicines such as rifampicin
- St John's wort (herbal remedy)

Do not take antacids at the same time that you take Digoxin. If you are taking antacids, take them 1 hour before or 2 hour after Digoxin.

Always inform your doctor if you are taking any other medicines, including herbal tonics, supplements and medicines that you buy without a prescription.

Food restrictions?

Avoid alcohol.

Do not take Digoxin together with high fibre foods such as cereals, high fibre bread, fruit or vegetables as it can reduce the absorption of Digoxin.

How to store this medicine?

Store in a cool, dry place away from the reach of children. Medicines must be used within the expiry date.

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