II. History
- Derived from Foxglove (Digitalis) plant
- Cardiac glycosides are also found in Lilly of the Valley
- Originally used as herbal tea to cure "Dropsy"
- First described by William Withering, England, 1775
III. Precautions
- Chronic Congestive Heart Failure
- Do not need to routinely follow Digoxin levels
- See Indications for Digoxin levels below
- Acute Congestive Heart Failure management (not recommended)
- High Digoxin Toxicity risk in critically ill patient
- Parenteral inotropes are preferred over Digoxin
- More potent
- Less toxicity
-
Atrial Fibrillation Rate Control (not recommended)
- Avoid Digoxin for Atrial Fibrillation Rate Control outside of comorbid CHF
- Increased mortaility when used for Atrial Fibrillation Rate Control
- Whitbeck (2012) Eur Heart J 10.1093/eurheartj/ehs348
IV. Mechanism
- Inotropic effect (Increases myocardial contractility)
- Inhibits membrane-bound sodium Potassium ATPase
- Increases Calcium in Sarcoplasmic Reticulum
- Increases myocardial contractility
- Not affected by Beta Adrenergic Receptor antagonist
- Not dependent on endogenous Catecholamines
- Less Potent than parenteral inotropes
- Inhibits membrane-bound sodium Potassium ATPase
-
Sinoatrial Node and Atrioventricular Node effects
- Accelerates atrial conduction
- Depresses conduction through AV Node
V. Indications
-
Paroxysmal Supraventricular Tachycardia (PSVT)
- Rarely used for PSVT, but can be considered in a hemodynamically stable patient
- Conversion to Normal Sinus Rhythm
- Chronic Congestive Heart Failure (Systolic Dysfunction)
- Third-line adjunct for symptomatic chronic Systolic Dysfunction
- Consider as adjunct if persistent symptoms despite ACE (or ARB), Beta Blocker, Diuretic and Aldosterone Antagonist
-
Atrial Fibrillation or Atrial Flutter
- Third line agent for Ventricular rate control
- Use in reduced ejection fraction
VI. Contraindications
- Avoid in Diastolic Dysfunction
VII. Drug Interactions
- Medications that increase Digoxin concentration
- Quinidine
- Verapamil
- Diltiazem
- Amiodarone
- Carvedilol
- Omeprazole (Prilosec)
- Propafenone
- Spironolactone (may yield falsely elevated levels)
- Medications that decrease Heart Rate and AV Conduction
- Medications that decrease Digoxin absorption
- Antacids (space administration 2 hours apart)
- Cholestyramine
- Colestipol
VIII. Pharmacokinetics
- Effects following intravenous dose
- Onset
- Intravenous: 5 to 30 minutes
- Oral: 30 minutes to 2 hours
- Peak: 1.5 to 3 hours
- Onset
- Half-Life: 36 hours
IX. Preparations
- Strengths (generic, $1/tab): 0.125 mg, 0.25 mg
- Strengths (trade, $2.50/tab): 0.0625 mg, 0.1875 mg
X. Dose
- Indications to lower Digoxin dose by 50%
- Drug Interactions (see above)
- Severe Renal Insufficiency (0.0625 mg daily)
- Chronic Congestive Heart Failure
- Standard Dose: 0.125 mg orally daily
- Low Dose: 0.0625 mg daily or 0.125 mg every other day
- Elderly patients
- Underweight patients
- Chronic Kidney Disease
- Rapid Atrial Fibrillation
- Rarely used for Atrial Fibrillation Rate Control in 2014
- See precautions above
- Indicated only if refractory or intollerant of other preferred agents (Metoprolol, Diltiazem)
- Load
- First Dose: 0.5 mg IV
- Second and Third Dose: 0.25 mg IV q6h for 2 doses
- Maintenance
- Start: 0.125 IV or orally daily
- May titrate dose to 0.375 mg IV or orally daily
- Target Heart Rate <80 resting and <110 on exertion
- Rarely used for Atrial Fibrillation Rate Control in 2014
XI. Labs: Digoxin level monitoring
- Low dose Digoxin does not require routine level monitoring (unless otherwise indicated)
- Indications
- Digoxin Toxicity suspected
- Elderly
- Chronic Kidney Disease
- Potential Drug Interactions (e.g. Amiodarone)
- Target level
- Targeting a specific drug level range is not typically indicated (outside of avoiding Digoxin Toxicity)
- Target is the lowest effective dose to control Heart Rate in Atrial Fibrillation or symptoms in Congestive Heart Failure
- Safe Digoxin range: 0.5 to 0.9 ng/ml
XII. Efficacy: Congestive Heart Failure (Stages C and D)
- Low doses (0.125 mg qd) are effective
- Digoxin Serum level 0.5 to 1.0 ng/ml
- Reduced morbidity
- Reduced Congestive Heart Failure signs and symptoms
- Neutral effect on mortality
- No benefit in acute Congestive Heart Failure
- RADIANCE trial (supports continued use of Digoxin)
XIII. Efficacy: Atrial Fibrillation
- Not recommended for Atrial Fibrillation Rate Control unless comorbid Congestive Heart Failure
- Not a great drug for rate control with activity
- Delayed onset of action
- Not first line for emergent rapid Atrial Fibrillation
- Higher mortality - see precautions below
XIV. References
- (2014) Presc Lett 21(4): 23
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Related Studies
digoxin (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
DIGOXIN 0.05 MG/ML SOLUTION | Generic | $0.63 per ml |
DIGOXIN 0.125 MG TABLET | Generic | $0.49 each |
DIGOXIN 0.25 MG TABLET | Generic | $0.56 each |
DIGOXIN 125 MCG TABLET | Generic | $0.49 each |
DIGOXIN 250 MCG TABLET | Generic | $0.56 each |
lanoxin (on 10/14/2016 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
LANOXIN 125 MCG TABLET | Generic | $0.49 each |
LANOXIN 250 MCG TABLET | Generic | $0.56 each |
Ontology: Digitalis Glycosides (C0012253)
Definition (MSH) | Glycosides from plants of the genus DIGITALIS. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all CARDIAC GLYCOSIDES, but here is restricted to those related to Digitalis. |
Concepts | Pharmacologic Substance (T121) , Carbohydrate (T118) |
MSH | D004071 |
SnomedCT | 91307002, 406759007, 387521006 |
English | Glycosides, Digitalis, DIGITALIS GLYCOSIDES, Digitalis Glycosides [Chemical/Ingredient], [CV050] DIGITALIS GLYCOSIDES, digitalis glycoside, digitalis glycosides, Digitalis glycosides, Digitalis glycoside, Digitalis glycoside (substance), Digitalis Glycosides |
Swedish | Digitalisglykosider |
Czech | digitalisové glykosidy |
Finnish | Digitalisglykosidit |
Russian | GLIKOZIDY NAPERSTIANKI, NAPERSTIANKI GLIKOZIDY, ГЛИКОЗИДЫ НАПЕРСТЯНКИ, НАПЕРСТЯНКИ ГЛИКОЗИДЫ |
Croatian | DIGITALIS, GLIKOZIDI |
Polish | Glikozydy naparstnicy |
Portuguese | Glicosídeos de Digitalis, Glicosídeos Digitálicos |
Spanish | glucósido digitálico, glucósido digitálico (sustancia), Glicósidos Digitálicos |
French | Digitale, glucosides, Glucosides digitaliques |
German | Digitalisglycoside |
Italian | Glicosidi digitali |
Ontology: Digoxin (C0012265)
Definition (NCI) | A cardiac glycoside. Digoxin inhibits the sodium potassium adenosine triphosphatase (ATPase) pump, thereby increasing intracellular calcium and enhancing cardiac contractility. This agent also acts directly on the atrioventricular node to suppress conduction, thereby slowing conduction velocity. Apparently due to its effects on intracellular calcium concentrations, digoxin induces apoptosis of tumor cells via a pathway involving mitochondrial cytochrome c and caspases 8 and 3. (NCI04) |
Definition (NCI_NCI-GLOSS) | A drug used to treat irregular heartbeat and some types of heart failure. It is also being studied in the treatment of some types of cancer. Digoxin helps the heart work normally by controlling the amount of calcium that goes into the heart muscle. It also may kill cancer cells and make them more sensitive to anticancer drugs. It is a type of cardiac glycoside. |
Definition (MSH) | A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666) |
Definition (CSP) | cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone digoxigenin; digoxin has positive inotropic and negative chronotropic activity; used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation; its use in congestive heart failure and sinus rhythm is less certain; the margin between toxic and therapeutic doses is small. |
Definition (PDQ) | A cardiac glycoside. Digoxin inhibits the sodium potassium adenosine triphosphatase (ATPase) pump, thereby increasing intracellular calcium and enhancing cardiac contractility. This agent also acts directly on the atrioventricular node to suppress conduction, thereby slowing conduction velocity. Apparently due to its effects on intracellular calcium concentrations, digoxin induces apoptosis of tumor cells via a pathway involving mitochondrial cytochrome c and caspases 8 and 3. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=485249&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=485249&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C28990" NCI Thesaurus) |
Concepts | Pharmacologic Substance (T121) , Steroid (T110) , Carbohydrate (T118) |
MSH | D004077 |
SnomedCT | 264300009, 387461009, 796001 |
LNC | LP14714-7, MTHU001808 |
English | Digoxin, Card-20(22)-enolide, 3-((O-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1-4)-O-2,6-dideoxy-beta-D-ribo-hexopyranosyl-(1-4)-2,6-dideoxy-beta-D-ribo-hexopyranosyl)oxy)-12,14-dihydroxy-, (3beta,5beta,12beta)-, digoxin, digoxin (medication), Digoxin - chemical, DIGOXIN, 3beta,12beta,14-Trihydroxy-5beta,14beta-card-20(22)-enolid-3-tridigitoxosid, Digoxigenin-tridigitoxosid, 12beta-Hydroxydigitoxin, Digoxin [Chemical/Ingredient], digoxin substance, Digoxin - chemical (substance), Digoxin product, Digoxin (product), Digoxin (substance) |
Swedish | Digoxin |
Czech | digoxin |
Finnish | Digoksiini |
Russian | DIGOKSIN, ДИГОКСИН |
Japanese | ジゴキシン |
Croatian | DIGOKSIN |
Polish | Digoksyna |
Spanish | digoxina (producto), digoxina (sustancia), digoxina, Digoxina |
French | Digoxine |
German | Digoxin |
Italian | Digossina |
Portuguese | Digoxina |
Ontology: Digitalis preparation (C0304520)
Definition (NCI_NCI-GLOSS) | A substance used to make drugs that are used to treat several heart conditions, including congestive heart failure. Digitalis is made from the dried leaves of Digitalis purpurea (common foxglove) plants. It is a type of cardiac glycoside. |
Definition (CSP) | extract from genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic digitalis glycosides; most useful species are Digitalis lanata and D. purpurea. |
Concepts | Pharmacologic Substance (T121) , Carbohydrate (T118) |
SnomedCT | 387521006, 91307002 |
English | Digitalis preparation, digitalis preparations, digitalis, DIGITALIS, Digitalis, Digitalis extract, Digitalis (substance), Digitalis preparation (product), Digitalis preparation (substance) |
Spanish | digitálico (sustancia), digital (sustancia), digitálico, digital, extracto digitálico, preparado digitálico (producto), preparado digitálico (sustancia), preparado digitálico |
Ontology: Lanoxin (C0699988)
Concepts | Pharmacologic Substance (T121) , Steroid (T110) , Carbohydrate (T118) |
MSH | D004077 |
English | digoxin injection (medication), digoxin injection, digoxin (Lanoxin) injection, Lanoxin, lanoxin, Lanoxin-PG, Glaxo Wellcome Brand of Digoxin, GlaxoSmithKline Brand 1 of Digoxin, Lanoxin PG, Lenoxin, Virco Brand of Digoxin |