What are the contraindications for digoxin therapy in patients with heart conditions, such as atrial fibrillation, ventricular fibrillation, or Wolff-Parkinson-White syndrome, and impaired renal function?

Digoxin Contraindications

Absolute Contraindications

Digoxin is absolutely contraindicated in patients with ventricular fibrillation, known hypersensitivity to digoxin or other digitalis preparations, and second- or third-degree heart block without a permanent pacemaker. 1, 2

Ventricular Fibrillation

• Digoxin is contraindicated in patients with ventricular fibrillation per FDA labeling 1

Heart Block

• Second- or third-degree atrioventricular block without a permanent pacemaker is an absolute contraindication 2, 3, 4
• Significant sinus node dysfunction (sick sinus syndrome) requires extreme caution and is often considered a contraindication unless a pacemaker is in place 2, 3

Pre-Excitation Syndromes (Wolff-Parkinson-White)

• Digoxin is potentially harmful and contraindicated in patients with WPW syndrome and atrial fibrillation or atrial flutter with manifest pre-excitation on ECG 5, 2
• The mechanism: digoxin slows AV nodal conduction but can facilitate antegrade conduction along the accessory pathway during atrial fibrillation, resulting in acceleration of ventricular rate, hypotension, or ventricular fibrillation 5
• Intravenous administration of digoxin, beta-blockers, adenosine, lidocaine, and nondihydropyridine calcium channel antagonists is specifically contraindicated in WPW patients with tachycardia associated with ventricular preexcitation 5

Hypersensitivity

• Known hypersensitivity to digoxin or previous digoxin intolerance constitutes an absolute contraindication 1, 2, 3

Critical Precautions and High-Risk Situations

Impaired Renal Function

• While not an absolute contraindication, severe renal impairment requires substantial dose reduction and close monitoring 1
• Patients with impaired renal function are at high risk for toxicity due to prolonged elimination half-life and reduced clearance 1, 6
• Start with 0.0625 mg daily in patients with marked renal impairment (CrCl <30 mL/min) 2, 3

Electrolyte Disturbances

• Hypokalemia and hypomagnesemia are not absolute contraindications but dramatically increase toxicity risk even at therapeutic digoxin levels 1, 4
• Hypercalcemia predisposes patients to digitalis toxicity; calcium administered rapidly IV can produce serious arrhythmias in digitalized patients 1
• Correct electrolyte abnormalities before initiating digoxin therapy 2, 3

Acute Myocardial Infarction

• Digoxin should be used with caution in acute MI settings, as inotropic drugs may increase myocardial oxygen demand and worsen ischemia 1

Thyroid Disorders

• Hypothyroidism may reduce digoxin requirements and increase toxicity risk 1, 4
• Hyperthyroidism makes atrial arrhythmias particularly resistant to digoxin treatment 1

Common Clinical Pitfalls

Drug Interactions That Increase Toxicity Risk

• Amiodarone, verapamil, diltiazem, quinidine, clarithromycin, erythromycin, itraconazole, cyclosporine, propafenone, dronedarone, and spironolactone all increase serum digoxin levels 2, 3, 4
• When adding these medications, reduce digoxin dose by 30-50% and monitor levels closely 2, 6

Combination with Other AV Nodal Blocking Agents

• Use digoxin cautiously when combined with beta-blockers, amiodarone, or nondihydropyridine calcium channel antagonists, as bradycardia and heart block may occur 5, 4
• This is particularly important in elderly patients and those with paroxysmal atrial fibrillation 5

Electrical Cardioversion

• Consider reducing digoxin dose 1-2 days before elective cardioversion of atrial fibrillation to avoid inducing ventricular arrhythmias 1
• If digitalis toxicity is suspected, delay elective cardioversion 1
• If cardioversion cannot be delayed, use the lowest possible energy level 1

Monitoring Requirements to Prevent Toxicity

• Mandatory serial monitoring of serum potassium, magnesium, and renal function (serum creatinine) 2, 1, 4
• Target serum digoxin concentration: 0.5-0.9 ng/mL for heart failure, 0.6-1.2 ng/mL for atrial fibrillation 2, 3
• Monitor for signs of toxicity: cardiac arrhythmias (ventricular arrhythmias, AV block, sinus bradycardia), gastrointestinal symptoms (anorexia, nausea, vomiting), and neurological symptoms (visual disturbances, confusion, disorientation) 2, 3, 4