Digoxin

Aka: Digoxin, Lanoxin, Digitalis, Digitalis Glycoside

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II. History

  1. Derived from Foxglove (Digitalis) plant
    1. Cardiac glycosides are also found in Lilly of the Valley
  2. Originally used as herbal tea to cure "Dropsy"
  3. First described by William Withering, England, 1775

III. Indications

  1. Paroxysmal Supraventricular Tachycardia (PSVT)
    1. Rarely used for PSVT, but can be considered in a hemodynamically stable patient
    2. Conversion to Normal Sinus Rhythm
  2. Chronic Congestive Heart Failure (Systolic Dysfunction)
    1. Third-line adjunct for symptomatic chronic Systolic Dysfunction
    2. Consider as adjunct if persistent symptoms despite ACE (or ARB), Beta Blocker, Diuretic and Aldosterone Antagonist
  3. Atrial Fibrillation or Atrial Flutter
    1. Third line agent for Ventricular rate control
    2. Use in reduced ejection fraction

IV. Contraindications

  1. Diastolic Dysfunction
  2. Severe Bradycardia
  3. Acute Coronary Syndrome
  4. Myocarditis
  5. Allergy to cardiac glycosides

V. Precautions

  1. Digoxin is proarrhythmic
    1. Dose cautiously in advanced age, comorbidity, Polypharmacy, impaired Renal Function and Electrolyte abnormalities
  2. Chronic Congestive Heart Failure
    1. Do not need to routinely follow Digoxin levels
    2. See Indications for Digoxin levels below
  3. Acute Congestive Heart Failure management (not recommended)
    1. High Digoxin Toxicity risk in critically ill patient
    2. Parenteral inotropes are preferred over Digoxin
      1. More potent
      2. Less toxicity
  4. Atrial Fibrillation Rate Control (not recommended for first line management)
    1. Avoid Digoxin for Atrial Fibrillation Rate Control outside of comorbid CHF
    2. Consider when Blood Pressure limits use of other rate control agents (e.g. Diltiazem, Metoprolol)
    3. Increased mortaility when used for Atrial Fibrillation Rate Control
    4. Whitbeck (2012) Eur Heart J 10.1093/eurheartj/ehs348
      1. http://eurheartj.oxfordjournals.org/content/early/2012/11/14/eurheartj.ehs348.full

VI. Mechanism

  1. Inotropic effect (Increases myocardial contractility)
    1. Inhibits membrane-bound sodium Potassium ATPase pump
      1. Increases Calcium in Sarcoplasmic Reticulum
      2. Increased Calcium influx increases myocardial contractility
      3. Results in increased Cardiac Output and venous return
      4. Results in increased renal perfusion and secondary diuresis
    2. Not affected by Beta Adrenergic ReceptorAntagonist
      1. Not dependent on endogenous Catecholamines
    3. Less Potent than Parenteral inotropes
  2. Sinoatrial Node and Atrioventricular Node effects
    1. Accelerates atrial conduction
    2. Depresses conduction through AV Node
      1. Increases AV Node sensitivity to Vagal Stimulation
  3. Peripheral Vascular Resistance Increased
    1. Increases venous return
    2. May also increase myocardial workload and risk Myocardial Ischemia

VII. Preparations

  1. Strengths (generic, $1/tab): 0.125 mg, 0.25 mg
  2. Strengths (trade, $2.50/tab): 0.0625 mg, 0.1875 mg

VIII. Dosing

  1. Dosing is oral or IV
    1. Do not use IM (risk of severe local reaction)
  2. Indications to lower Digoxin dose by 50%
    1. Drug Interactions (see above)
    2. Severe Renal Insufficiency (0.0625 mg daily)
  3. Chronic Congestive Heart Failure
    1. Standard Dose: 0.125 mg orally daily (maximum dose 0.25 mcg daily)
    2. Low Dose: 0.0625 mg daily or 0.125 mg every other day
      1. Elderly patients
      2. Underweight patients
      3. Chronic Kidney Disease
  4. Rapid Atrial Fibrillation
    1. Rarely used for Atrial Fibrillation Rate Control in 2014
      1. See precautions above
      2. Indicated only if refractory or intolerant of other preferred agents (Metoprolol, Diltiazem)
    2. Load
      1. First Dose: 0.5 mg IV
        1. Impaired Renal Function: 0.25 IV
      2. Second and Third Dose: 0.25 mg IV every 6 hours for 2 doses
        1. Impaired Renal Function: 0.125 IV every 6 hours for 2 doses
      3. Total loading dose 10 to 15 mcg/kg IV or oral divided in 3 doses every 6 to 8 hours
        1. Impaired Renal Function: 6 to 10 mcg/kg divided into 3 doses
    3. Maintenance
      1. Start: 0.125 IV or orally daily
      2. May titrate dose to 0.375 mg IV or orally daily
        1. Target Heart Rate <80 resting and <110 on exertion

IX. Labs: Digoxin Level Monitoring

  1. Low dose Digoxin does not require routine level monitoring (unless otherwise indicated)
  2. Indications
    1. Digoxin Toxicity suspected
    2. Elderly
    3. Chronic Kidney Disease
    4. Potential Drug Interactions (e.g. Amiodarone)
  3. Target level
    1. Targeting a specific drug level range is not typically indicated (outside of avoiding Digoxin Toxicity)
    2. Target is the lowest effective dose to control Heart Rate in Atrial Fibrillation or symptoms in Congestive Heart Failure
    3. Safe Digoxin range: 0.5 to 0.9 ng/ml

X. Adverse Effects

  1. See Digoxin Toxicity
  2. Bradycardia
  3. AV Node Block
  4. Anorexia
  5. Nausea or Vomiting
  6. Diarrhea
  7. Headache
  8. Fatigue
  9. Malaise
  10. Visual disturbance (e.g. color changes)
  11. Gynecomastia

XI. Safety

  1. Pregnancy Category C
  2. Considered safe in Lactation

XII. Drug Interactions

  1. See Digoxin Toxicity
  2. Medications that increase Digoxin concentration
    1. Quinidine
    2. Verapamil
    3. Diltiazem
    4. Amiodarone
    5. Carvedilol
    6. Omeprazole (Prilosec)
    7. Propafenone
    8. Spironolactone (may yield falsely elevated levels)
  3. Medications that decrease Heart Rate and AV Conduction (risk of AV Block)
    1. Verapamil
    2. Diltiazem
    3. Amiodarone
    4. Beta Blockers
    5. Propafenone
    6. Sotalol
  4. Medications that decrease Digoxin absorption
    1. Antacids (space administration 2 hours apart)
    2. Cholestyramine
    3. Colestipol

XIII. Pharmacokinetics

  1. Half-Life: 36 hours
  2. Protein Bound 25%
  3. Excreted unchanged in urine
  4. Effects following intravenous dose
    1. Onset
      1. Intravenous: 5 to 30 minutes
      2. Oral: 30 minutes to 2 hours
    2. Peak: 1.5 to 3 hours

XIV. Efficacy: Congestive Heart Failure (Stages C and D)

  1. Low doses (0.125 mg qd) are effective
    1. Digoxin Serum level 0.5 to 1.0 ng/ml
    2. Reduced morbidity
    3. Reduced Congestive Heart Failure signs and symptoms
    4. Neutral effect on mortality
    5. No benefit in acute Congestive Heart Failure
  2. RADIANCE trial (supports continued use of Digoxin)
    1. Packer (1993) N Engl J Med 329:1-7 [PubMed]
    2. Smith (1993) N Engl J Med 329:51-53 [PubMed]

XV. Efficacy: Atrial Fibrillation

  1. Not recommended for Atrial Fibrillation Rate Control unless comorbid Congestive Heart Failure
  2. Not a great drug for rate control with activity
  3. Delayed onset of action
  4. Not first line for emergent rapid Atrial Fibrillation
  5. Higher mortality - see precautions below

XVI. Resources

  1. Digoxin Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=41c16cff-b03e-405e-a617-d6f45d3ce2bd

XVII. References

  1. (2014) Presc Lett 21(4): 23
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 74-5
  3. Dec (2003) Med Clin North Am 87(2):317-37 +PMID: 12693728 [PubMed]
  4. Virgadamo (2015) World J Cardiol 7(11):808-16 +PMID: 26635929 [PubMed]

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Related Studies

Cost: Medications

digoxin (on 3/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
DIGOXIN 0.05 MG/ML SOLUTION Generic $1.98 per ml
DIGOXIN 0.125 MG TABLET Generic $0.18 each
DIGOXIN 0.25 MG TABLET Generic $0.19 each
DIGOXIN 125 MCG TABLET Generic $0.18 each
DIGOXIN 250 MCG TABLET Generic $0.19 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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
Derived from the NIH UMLS (Unified Medical Language System)

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
Derived from the NIH UMLS (Unified Medical Language System)

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
Derived from the NIH UMLS (Unified Medical Language System)

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
Derived from the NIH UMLS (Unified Medical Language System)

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