Table 13. Dosage and Safety Considerations for Maintenance of Sinus Rhythm in AF.

Drug	Usual Doses	Exclude/Use with Caution	Major 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 Diuretic therapy Avoid other QT interval prolonging drugs	Metabolized by CYP3A: 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 Diuretic therapy Avoid other QT interval prolonging drugs Sinus or AV nodal dysfunction HF Asthma	None (renal excretion)

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.

Adapted from Roden et al. (369).