Table 13

Dosage and Safety Considerations for Maintenance of Sinus Rhythm in AF

DrugUsual DosesExclude/Use With CautionMajor Pharmacokinetic Drug Interactions
Vaughan Williams class IA
 Disopyramide
  • Immediate release: 100–200 mg once every 6 h

  • Extended release: 200–400 mg once every 12 h

  • HF

  • Prolonged QT interval

  • Prostatism, glaucoma

  • Avoid other QT interval−prolonging drugs

  • Metabolized by CYP3A4: caution with inhibitors (e.g., verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, grapefruit juice) and inducers (e.g., rifampin, phenobarbital, phenytoin)

 Quinidine
  • 324–648 mg every 8 h

  • Prolonged QT interval

  • Diarrhea

  • Inhibits CYP2D6: ↑concentrations of tricyclic antidepressants, metoprolol, antipsychotics; ↓efficacy of codeine

  • Inhibits P-glycoprotein: ↑digoxin concentration

Vaughan Williams class IC
 Flecainide
  • 50–200 mg once every 12 h

  • Sinus or AV node dysfunction

  • HF

  • CAD

  • Atrial flutter

  • Infranodal conduction disease

  • Brugada syndrome

  • Renal or liver disease

  • Metabolized by CYP2D6 (inhibitors include quinidine, fluoxetine, tricyclics; also genetically absent in 7%–10% of population) and renal excretion (dual impairment can ↑↑plasma concentration)

 Propafenone
  • Immediate release: 150–300 mg once every 8 h

  • Extended release: 225–425 mg once every 12 h

  • Sinus or AV node dysfunction

  • HF

  • CAD

  • Atrial flutter

  • Infranodal conduction disease

  • Brugada syndrome

  • Liver disease

  • Asthma

  • Metabolized by CYP2D6 (inhibitors include quinidine, fluoxetine, tricyclics; also genetically absent in 7%–10% of population)—poor metabolizers have ↑beta blockade

  • Inhibits P-glycoprotein: ↑digoxin concentration

  • Inhibits CYP2C9: ↑warfarin concentration (↑INR 25%)

Vaughan Williams class III
 Amiodarone
  • Oral: 400–600 mg daily in divided doses for 2–4 wk; maintenance typically 100−200 mg QD

  • IV: 150 mg over 10 min; then 1 mg/min for 6 h; then 0.5 mg/min for 18 h or change to oral dosing; after 24 h, consider decreasing dose to 0.25 mg/min

  • Sinus or AV node dysfunction

  • Infranodal conduction disease

  • Lung disease

  • Prolonged QT interval

  • Inhibits most CYPs to cause drug interaction: ↑concentrations of warfarin (↑INR 0%–200%), statins, many other drugs

  • Inhibits P-glycoprotein: ↑digoxin concentration

 Dofetilide
  • 125–500 mcg once every 12 h

  • Prolonged QT interval

  • Renal disease

  • Hypokalemia

  • Hypomagnesemia

  • Diuretic therapy

  • Avoid other QT interval−prolonging drugs

  • Primary renal elimination involving glomerular filtration and active tubular secretion: verapamil, HCTZ, cimetidine, ketoconazole, trimethoprim, prochlorperazine, and megestrol are contraindicated; discontinue amiodarone at least 3 mo before initiation

 Dronedarone
  • 400 mg once every 12 h

  • Bradycardia

  • HF

  • Long-standing persistent AF/flutter

  • Liver disease

  • Prolonged QT interval

  • Metabolized by CYP3A: caution with inhibitors (e.g., verapamil, diltiazem, ketoconazole, macrolide antibiotics, protease inhibitors, grapefruit juice) and inducers (e.g., rifampin, phenobarbital, phenytoin)

  • Inhibits CYP3A, CYP2D6, P-glycoprotein: ↑concentrations of some statins, sirolimus, tacrolimus, beta blockers, digoxin

 Sotalol
  • 40–160 mg once every 12 h

  • Prolonged QT interval

  • Renal disease

  • Hypokalemia

  • Hypomagnesemia

  • Diuretic therapy

  • Avoid other QT interval−prolonging drugs

  • Sinus or AV nodal dysfunction

  • HF

  • Asthma

  • None (renal excretion)

Adapted with permission from Roden et al. (369).

AF indicates atrial fibrillation; AV, atrioventricular; CAD, coronary artery disease; HCTZ, hydrochlorothiazide; HF, heart failure; INR, international normalized ratio; IV, intravenous; and QD, once daily.