CLASS
Antiarrhythmic, inotrope
PRESENTATION
Clear colourless solution, tablets, elixir.
Formulations
- IV; 2ml vial, 500mcg, 250mcg/ml
- Tablets; 250mcg, 62.5mcg
- Elixir; 50mcg/ml
INDICATIONS & DOSING
Rate control in atrial flutter/fibrillation tachycardia
Congestive cardiac failure
- Adult; loading dose 250-500mcg IV, subsequent doses 100-300mcg IV Q6H until adequate response, maintenance 62.5-250mcg PO Q6H, max daily dose 1.5mg
- Paediatric; specific age-based dosing schedule, refer to literature
PRACTICALITIES
Administration
- Slow IV bolus over 5 minutes to avoid hypertension
Practice tips
- Less efficacious for management of arrhythmias perioperatively as commonly driven by increased sympathetic tone
- Ineffective at chemical cardioversion of AF or preventing recurrence of AF post cardioversion
- Dose reduction by ~50% recommended in the elderly and renal impairment (CrCl <60ml/min)
- Not removed by dialysis
- Requires dose monitoring to prevent toxicity; therapeutic range 1-2μg/L, toxic range >2.5μg/L (significant >10μg/L)
- The ECG signs of the digoxin effect are not indicative of toxicity; prolonged PR, characteristic ST segment depression, T-wave flattening, shortened QT (Salvador Dali’s moustache)
PHARMACOKINETICS
Onset
- IV; 5-30 minutes, peak effect ~2-3 hours
- PO; 0.5-2 hours, peak effect ~3-5 hours
Duration of action
- 3-4 days upon cessation of maintenance dosing
Metabolism
<10% undergoes hepatic metabolism
Elimination
50-70% excreted unchanged in urine, clearance largely dependent on renal function
MECHANISM
Dual mechanism of action; positive isotropy due to increased intracellular calcium concentration (via inhibition of cardiac Na/K/ATPase and subsequent Ca-exchange), and negative dromotropy due to relative intracellular hypokalaemia and indirectly via increased parasympathetic tone.
DESIRED CLINICAL EFFECTS
Cardiovascular
- Depression of SA node automaticity, depression of AV node conduction, increase in AV refractory period; rate control of atrial arrhythmias
- Increased cardiac contractility, cardiac output
OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES
Cardiovascular
- Increased atrial and ventricular automaticity with potential for dysrhythmias; atrial tachycardia, ventricular ectopy/bigemini/tachycardia
- Depression of AV node conduction, increase in AV refractory period with potential for dysrhythmias; 1st/2nd/3rd degree heart block, junctional bradycardia
- In toxicity atrial tachycardias with high-grade conduction deficit a common presentation
- Rapid IV dosing: peripheral vasoconstriction, hypertension
Neurological
- Headache, lethargy, confusion
- Reduced GCS in toxicity
- Visual disturbance; deranged red/green vision
Renal & electrolytes
- Hyperkalaemia
- Mild diuretic action
Gastrointestinal
- Anorexia, nausea/vomiting, diarrhoea
- Abdominal pain
Other
- Muscle weakness
- Rash
- Gynaecomastia
Antidote
- Digoxin-specific antibody (IgG fragments, renally excreted)
CONSIDERATIONS
Precautions
- Sinus dysfunction, high-grade AV conduction block; worsening of conduction block
- Ventricular extrasystoles, ventricular tachycardia; increased risk of ventricular fibrillation
- Wolff-Parkinson-White with atrial fibrillation, atrial flutter, antidromic AVRT; may facilitate conduction via accessory tract, leading to rapid ventricular response and degeneration to ventricular tachycardia/fibrillation
- Renal impairment, hyperthyroidism, hypokalaemia, hypercalcaemia, hypomagnesaemia, hypernatraemia, pH disturbances, hypoxaemia; increased risk of digoxin toxicity
- Myocardial ischaemia/failure/myocarditis, severe pulmonary disease; increased risk of digoxin-induced arrhythmias
- Myocardial ischaemia; increased oxygen demand, worsening of ischaemia
- Diuretics; increased risk of electrolyte disturbances
- Hypertrophic obstructive cardiomyopathy; worsening of outflow obstruction
- Carotid sinus hypersensitivity; worsening of vagal tone
Obstetric
ADEC category A
Drug interactions
- Suxamethonium, pancuronium; increased risk of dysrhythmias
- Beta-adrenergic agonists; increased risk of dysrhythmias
- Verapamil (and to a lesser extent diltiazem, nifedipine), amiodarone, diazepam, erythromycin; increased digoxin plasma concentration
- Antacids, metoclopramide, phenytoin; reduced digoxin plasma concentration
- Adenosine; risk of ventricular fibrillation
REFERENCES
Drug information has been compiled from multiple sources including
- Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
- Micromedex (IBM)
- BJA Education (Oxford Academic)
- Pharmacology for Anaesthesia and Intensive Care (Cambridge)
- Australian Prescriber (NPS MedicineWise)