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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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.

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