Digoxin

Aka: Digoxin, Lanoxin, Digitalis, Digitalis Glycoside

1. 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
2. Precautions
   1. Chronic Congestive Heart Failure
      1. Do not need to routinely follow Digoxin levels
      2. See Indications for Digoxin levels below
   2. 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
   3. Atrial Fibrillation Rate Control (not recommended)
      1. Avoid Digoxin for Atrial Fibrillation Rate Control outside of comorbid CHF
      2. Increased mortaility when used for Atrial Fibrillation Rate Control
      3. Whitbeck (2012) Eur Heart J 10.1093/eurheartj/ehs348
         1. http://eurheartj.oxfordjournals.org/content/early/2012/11/14/eurheartj.ehs348.full
3. Mechanism
   1. Inotropic effect (Increases myocardial contractility)
      1. Inhibits membrane-bound sodium Potassium ATPase
         1. Increases Calcium in Sarcoplasmic Reticulum
         2. Increases myocardial contractility
      2. Not affected by Beta Adrenergic Receptor antagonist
         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
4. 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
5. Contraindications
   1. Avoid in Diastolic Dysfunction
6. Drug Interactions
   1. 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)
   2. Medications that decrease Heart Rate and AV Conduction
      1. Verapamil
      2. Diltiazem
      3. Amiodarone
      4. Beta Blockers
      5. Propafenone
      6. Sotalol
   3. Medications that decrease Digoxin absorption
      1. Antacids (space administration 2 hours apart)
      2. Cholestyramine
      3. Colestipol
7. Pharmacokinetics
   1. 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
   2. Half-Life: 36 hours
8. Preparations
   1. Strengths (generic, $1/tab): 0.125 mg, 0.25 mg
   2. Strengths (trade, $2.50/tab): 0.0625 mg, 0.1875 mg
9. Dose
   1. Indications to lower Digoxin dose by 50%
      1. Drug Interactions (see above)
      2. Severe Renal Insufficiency (0.0625 mg daily)
   2. Chronic Congestive Heart Failure
      1. Standard Dose: 0.125 mg orally 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
   3. Rapid Atrial Fibrillation
      1. Rarely used for Atrial Fibrillation Rate Control in 2014
         1. See precautions above
         2. Indicated only if refractory or intollerant of other preferred agents (Metoprolol, Diltiazem)
      2. Load
         1. First Dose: 0.5 mg IV
         2. Second and Third Dose: 0.25 mg IV q6h for 2 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
10. 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
11. 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]
12. 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
13. References
    1. (2014) Presc Lett 21(4): 23