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How to load digoxin

  • Loading dose
    • IV
      • Digoxin loading dose IV:  500mcg; followed by 250mcg 6 hours later and a further 250mcg 6 hours after that
    • PO
      • Digoxin loading oral: 500-750mcg 2 doses 6 hours apart (max 1500mcg in 24 hours)
  • Maintenance dose
    • 62.5mcg – 250mcg daily
    • Note: when converting from the oral to the IV formulation the dosage should be reduced by 33% to take account of the difference in bioavailability


Dose adjustments

  • Dose in renal impairment [GFR (ml/min)]
    • <10: 62.5mcg three times a week to 62.5mcg daily
    • 10-20: usually 125mcg daily
    • >20-50: usually 125mcg daily
  • Note: for patients with renal impairment interval between doses given during digitalisation should be lengthened to for example 8-10 hours.


Pharmacology of digoxin

  • Digoxin inhibits sodium-potassium ATPase. This increases intracellular sodium and thus (by stimulation of sodium-calcium exchange) an increase in the intracellular concentration of calcium.
  • The beneficial effects of digoxin result from direct actions on cardiac muscle, as well as indirect actions on the cardiovascular system mediated by effects on the autonomic nervous system.


Contraindications to digoxin

  • Hypersensitivity to digoxin


Cautions with digoxin

  • Sinus Node Disease and AV Block
    • Because digoxin slows SA and AV conduction, it commonly prolongs the PR interval.
    • May cause severe sinus bradycardia or sinoatrial block in patients with pre-existing sinus node disease and may cause advanced or complete heart block in patients with pre-existing incomplete AV block.
  • Accessory AV Pathway (Wolff-Parkinson-White Syndrome)
    • After intravenous digoxin therapy, some patients with paroxysmal atrial fibrillation or flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, leading to a very rapid ventricular response or ventricular fibrillation.
  • Electrolyte imbalance
    • In patients with hypokalemia or hypomagnesemia, toxicity may occur despite serum digoxin concentrations below 2.0 ng/ml, because potassium or magnesium depletion sensitizes the myocardium to digoxin.
    • Hypercalcemia from any cause predisposes the patient to digitalis toxicity. Calcium, particularly when administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. On the other hand, hypocalcemia can nullify the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal.


Tips for digoxin

  • Always ensure potassium, magnesium and calcium are replaced prior to digitalising


Laboratory Tests

  • Digoxin toxicity may develop in the critically ill, particularly if the patient has renal impairment. Monitoring is not routinely required but should be considered.
  • Therapeutic Range 0.6-1.2 nmol/L. Recommended sampling: 8-24 hours post dose.
  • If a patient is commenced on digoxin in the ICU levels should not be measured until the drug has achieved steady state at 5-7 days.


Interactions with digoxin

  • Potassium-depleting diuretics are a major contributing factor to digitalis toxicity.
  • 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 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 may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result.
  • Rifampin may decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin.


Adverse effects of digoxin

  • Cardiovascular
    • Ventricular extrasystoles, tachycardia, bradycardias, heart block, cardiac arrest
  • Gastrointestinal
    • Anorexia, nausea, vomiting, diarrhoea, abdominal pain
  • CNS
    • Headache, dizziness, mental disturbances, visual disturbances.