Digoxin: Difference between revisions
Line 261: | Line 261: | ||
==Drug Interactions== | ==Drug Interactions== | ||
* | *Potassium-depleting diuretics | ||
* | *Calcium | ||
* | *Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone | ||
* | *Erythromycin, clarithromycin, and tetracycline | ||
* | *Propantheline and diphenoxylate | ||
*Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, and metoclopramide | |||
*Rifampin | |||
*Thyroxine | |||
*Sympathomimetics | |||
*Succinylcholine | |||
*Calcium Channel Blockers | |||
*Beta blockers | |||
===== | =====Potassium-depleting diuretics===== | ||
Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. | |||
===== | =====Calcium===== | ||
Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. | |||
===== | =====Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone===== | ||
Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result. | |||
===== | =====Erythromycin, clarithromycin, and tetracycline===== | ||
( | Erythromycin and clarithromycin (and possibly othermacrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result (see ''[[{{PAGENAME}}#Pharmacology|Pharmacology]]''). | ||
=====Propantheline and diphenoxylate===== | |||
Decrease gut motility, which may increase digoxin absorption. | |||
=====Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, and metoclopramide===== | |||
May interfere with intestinal digoxin absorption, resulting in unexpectedly low serum concentrations. | |||
===== Rifampin===== | |||
May decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin. | |||
=====Thyroxine===== | |||
Thyroid administration to a digitalized, [[hypothyroid ]]patient may increase the dose requirement of digoxin. | |||
=====Sympathomimetics===== | |||
Concomitant use of digoxin and [[sympathomimetics ]]increases the risk of cardiac arrhythmias. | |||
=====Succinylcholine===== | |||
[[Succinylcholine ]]may cause a sudden extrusion of potassium from muscle cells, and may thereby cause [[arrhythmias ]]in digitalized patients. | |||
=====Calcium Channel Blockers===== | |||
Use with digoxin may be useful in combination to control atrial fibrillation, their additive effects on [[AV node]] conduction can result in advanced or [[complete heart block]]. | |||
=====Beta blockers===== | |||
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of [[bradycardia]]. Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing [[carvedilol]]. | |||
==Use in Specific Populations== | ==Use in Specific Populations== |
Revision as of 15:02, 31 March 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
Synonyms / Brand Names: Digox; Lanoxin
Disclaimer
WikiDoc Drug Project is a constellation of drug information for healthcare providers and patients vigorously vetted on the basis of FDA package insert, MedlinePlus, Practice Guidelines, Scientific Statements, and scholarly medical literature. The information provided is not a medical advice or treatment. WikiDoc does not promote any medication or off-label use of drugs. Please read our full disclaimer here.
Black Box Warning
FDA Package Insert for Digoxin contains no information regarding Black Box Warning.
Overview
Digoxin is a cardiac glycoside drug that is FDA approved for the treatment of atrial fibrillation, atrial flutter, and heart failure. Common adverse reactions include dizziness, headache, mental disorder, nausea, and vomiting.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Heart failure
- Dosing Information
- Loading dose: Oral10-15 mcg/kg half of dose administered initially, and the other two quarters are given every 6-8 hours twice.
Intravenous 8-12 mcg/kg half of the dose is given initially, and the other two quarters are given each 6-8 hours in two doses.
- Maintenance dose: Oral3.4-5.1 mcg/kg/day once daily.
Intravenous 2.4-3.6 mcg/kh/day once daily.
Atrial fibrillation
- Dosing Information
- Loading dose: Oral 10-15 mcg/kg PO half of dose administered initially, and the other two quarters are given every 6-8 hours twice.
Intravenous 8-12 mcg/kg half of the dose is given initially, and the other two quarters are given each 6-8 hours in two doses.
- Maintenance dose: Oral 3.4-5.1 mcg/kg/day PO once daily.
Intravenous 2.4-3.6 mcg/kh/day once daily.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Non–Guideline-Supported Use
Condition 1
- Dosing Information
- (Dosage)
Condition 2
- Dosing Information
- (Dosage)
Condition 3
- Dosing Information
- (Dosage)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Heart failure
- Dosing Information
- Loading dose
- 5-10 years old: 20-45 mcg/kg Administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice.
- >10 year old: 10-15 mcg/kg Administer half the total loading dose initially, then ¼ the loading dose every 6 to 8 hours twice.
- Maintenence dose:
- 2-5 years: 10-15 mcg/kg/day.
- 5-10 years: 7-10 mcg/kg/day.
- More than 10 years: 3-5 mcg/kg/day.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Non–Guideline-Supported Use
Supraventricular tachycardia, Recurrent; Prophylaxis
- Dosage information
Fetal tachycardia - Supraventricular tachycardia
- Dosage information
Contraindications
- Condition 1
- Condition 2
- Condition 3
- Condition 4
- Condition 5
Warnings
Ventricular Fibrillation in Patients With 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.
Sinus Bradycardia and Sino-atrial Block
Digoxin may cause severe sinus bradycardia or sino-atrial 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. Consider insertion of a pacemaker before treatment with digoxin.
Digoxin Toxicity
Signs and symptoms of digoxin toxicity include anorexia, nausea, vomiting, visual changes and cardiac arrhythmias [first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation]. Toxicity is usually associated with digoxin levels greater than 2 ng/mL although symptoms may also occur at lower levels. Low body weight, advanced age or impaired renal function, hypokalemia, hypercalcemia, or hypomagnesemia may predispose to digoxin toxicity. Obtain serum digoxin levels in patients with signs or symptoms of digoxin therapy and interrupt or adjust dose if necessary [see Adverse Reactions (6) and Overdosage (10)]. Assess serum electrolytes and renal function periodically. The earliest and most frequent manifestation of digoxin toxicity in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia. In children, the use of digoxin may produce any arrhythmia. The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmias or alteration in cardiac conduction that develops in a child taking digoxin should initially be assumed to be a consequence of digoxin intoxication.
Misidentification of Digoxin Toxicity
Given that adult patients with heart failure have some symptoms in common with digoxin toxicity, it may be difficult to distinguish digoxin toxicity from 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 clear, measure serum digoxin levels.
Risk of Ventricular Arrhythmias During Electrical Cardioversion
It may be desirable to reduce the dose of or discontinue digoxin for 1-2 days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular arrhythmias, but physicians must consider the consequences of increasing the ventricular response if digoxin is decreased or withdrawn. If digitalis toxicity is suspected, elective cardioversion should be delayed. If it is not prudent to delay cardioversion, the lowest possible energy level should be selected to avoid provoking ventricular arrhythmias.
Risk of Ischemia in Patients With Acute Myocardial Infarction
Digoxin is not recommended in patients with acute myocardial infarction because digoxin may increase myocardial oxygen demand and lead to ischemia.
Vasoconstriction in Patients With Myocarditis
Digoxin can precipitate vasoconstriction and may promote production of pro-inflammatory cytokines; therefore, avoid use in patients with myocarditis.
Decreased Cardiac Output in Patients With Preserved Left Ventricular Systolic Function
Patients with heart failure associated with preserved left ventricular ejection fraction may experience decreased cardiac output with use of digoxin. Such disorders include restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathic hypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic effects of digoxin. Patients with amyloid heart disease may be more susceptible to digoxin toxicity at therapeutic levels because of an increased binding of digoxin to extracellular amyloid fibrils. Digoxin should generally be avoided in these patients, although it has been used for ventricular rate control in the subgroup of patients with atrial fibrillation.
Reduced Efficacy in Patients With Hypocalcemia
Hypocalcemia can nullify the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal. These interactions are related to the fact that digoxin affects contractility and excitability of the heart in a manner similar to that of calcium.
Altered Response in Thyroid Disorders and Hypermetabolic States
Hypothyroidism may reduce the requirements for digoxin. Heart failure and/or 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 are particularly resistant to digoxin treatment. Patients with beri beri heart disease may fail to respond adequately to digoxin if the underlying thiamine deficiency is not treated concomitantly.
Adverse Reactions
Clinical Trials Experience
Nervous System
- Visual disturbances (blurred or yellow vision), headache, weakness, dizziness, apathy, confusion, and mental disturbances (such as anxiety, depression, delirium, and hallucination).
Cardiovascular
- Arrhythmia( first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation).
Gastrointestinal
Miscellaneous
- Gynecomastia, thrombocytopenia and maculopapular rash.
Infant and Children
The side effects of digoxin in infants and children differ from those seen in adults in several respects. Although digoxin may produce anorexia, nausea, vomiting, diarrhea, and CNS disturbances in young patients, these are rarely the initial symptoms of overdosage. Rather, the earliest and most frequent manifestation of excessive dosing with digoxin in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia. In children, the use of digoxin may produce any arrhythmia. The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin, until further evaluation proves otherwise.
Postmarketing Experience
FDA Package Insert for digoxin tablet contains no information regarding 'Postmarketing Experience'.
Drug Interactions
- Potassium-depleting diuretics
- Calcium
- Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone
- Erythromycin, clarithromycin, and tetracycline
- Propantheline and diphenoxylate
- Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, and metoclopramide
- Rifampin
- Thyroxine
- Sympathomimetics
- Succinylcholine
- Calcium Channel Blockers
- Beta blockers
Potassium-depleting diuretics
Potassium-depleting diuretics are a major contributing factor to digitalis toxicity.
Calcium
Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients.
Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone
Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result.
Erythromycin, clarithromycin, and tetracycline
Erythromycin and clarithromycin (and possibly othermacrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result (see Pharmacology).
Propantheline and diphenoxylate
Decrease gut motility, which may increase digoxin absorption.
Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine, certain anticancer drugs, and metoclopramide
May interfere with intestinal digoxin absorption, resulting in unexpectedly low serum concentrations.
Rifampin
May decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin.
Thyroxine
Thyroid administration to a digitalized, hypothyroid patient may increase the dose requirement of digoxin.
Sympathomimetics
Concomitant use of digoxin and sympathomimetics increases the risk of cardiac arrhythmias.
Succinylcholine
Succinylcholine may cause a sudden extrusion of potassium from muscle cells, and may thereby cause arrhythmias in digitalized patients.
Calcium Channel Blockers
Use with digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block.
Beta blockers
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol.
Use in Specific Populations
Pregnancy
- Pregnancy Category (AUS): Digoxin is not included in Australian Drug Evaluation Committee (ADEC) Pregnancy Categories.
(Description)
Labor and Delivery
(Description)
Nursing Mothers
(Description)
Pediatric Use
(Description)
Geriatric Use
(Description)
Gender
(Description)
Race
(Description)
Renal Impairment
(Description)
Hepatic Impairment
(Description)
Carcinogenesis, Mutagenesis, Impairment of Fertility
(Description)
Immunocompromised Patients
(Description)
Miscellaneous
(Description)
Administration and Monitoring
Administration
(Oral/Intravenous/etc)
Monitoring
Condition 1
(Description regarding monitoring, from Warnings section)
Condition 2
(Description regarding monitoring, from Warnings section)
Condition 3
(Description regarding monitoring, from Warnings section)
IV Compatibility
Solution
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Y-Site
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Admixture
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Syringe
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
TPN/TNA
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Overdosage
Acute Overdose
Signs and Symptoms
(Description)
Management
(Description)
Chronic Overdose
Signs and Symptoms
(Description)
Management
(Description)
Pharmacology
Digoxin
| |
Systematic (IUPAC) name | |
? | |
Identifiers | |
CAS number | ? |
ATC code | ? |
PubChem | ? |
Chemical data | |
Formula | ? |
Mol. mass | ? |
Pharmacokinetic data | |
Bioavailability | ? |
Metabolism | ? |
Half life | ? |
Excretion | ? |
Therapeutic considerations | |
Pregnancy cat. |
? |
Legal status | |
Routes | ? |
Mechanism of Action
(Description)
Structure
(Description with picture)
Pharmacodynamics
(Description)
Pharmacokinetics
(Description)
Nonclinical Toxicology
(Description)
Clinical Studies
Condition 1
(Description)
Condition 2
(Description)
Condition 3
(Description)
How Supplied
(Description)
- National Drug Code (NDC):
- Storage:
- Manufactured by:
- Distributed by:
Images
Drug Images
Package and Label Display Panel
(Package Images)
(Display Panel Images)
Patient Information
Patient Information from FDA
(Patient Counseling Information)
Patient Information from NLM
(Link to patient information page)
Precautions with Alcohol
Alcohol-Digoxin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
Brand Names®
Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
Drug Shortage Status
Price
References
- ↑ Pfammatter, JP.; Stocker, FP. (1998). "Re-entrant supraventricular tachycardia in infancy: current role of prophylactic digoxin treatment". Eur J Pediatr. 157 (2): 101–6. PMID 9504781. Unknown parameter
|month=
ignored (help) - ↑ Sanatani, S.; Potts, JE.; Reed, JH.; Saul, JP.; Stephenson, EA.; Gibbs, KA.; Anderson, CC.; Mackie, AS.; Ro, PS. (2012). "The study of antiarrhythmic medications in infancy (SAMIS): a multicenter, randomized controlled trial comparing the efficacy and safety of digoxin versus propranolol for prophylaxis of supraventricular tachycardia in infants". Circ Arrhythm Electrophysiol. 5 (5): 984–91. doi:10.1161/CIRCEP.112.972620. PMID 22962431. Unknown parameter
|month=
ignored (help) - ↑ Lilja, H.; Karlsson, K.; Lindecrantz, K.; Sabel, KG. (1984). "Treatment of intrauterine supraventricular tachycardia with digoxin and verapamil". J Perinat Med. 12 (3): 151–4. PMID 6502442.