Abstract
The chemical and pharmacologic properties, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, and dosage of propafenone are reviewed. Propafenone is a class IC antiarrhythmic agent that is structurally similar to the β blockers but that has only weak β-blocking and calcium-channel-blocking activity. It is well absorbed after oral administration, but systemic bioavailability is only 12% after a 300-mg dose. Among extensive metabolizers (> 90% of the United States population), bioavailability seems to vary nonlinearly with dose and increases substantially with food; these effects are not seen in poor metabolizers. Elimination is primarily hepatic, with a mean elimination half-life after oral administration of 5.5 hours in extensive metabolizers and 17.2 hours in poor metabolizers. The relationship between plasma propafenone concentration and clinical response varies considerably among individual patients; therefore, plasma concentrations have limited usefulness in predicting efficacy or electrophysiologic effects. Propafenone is effective in treating ventricular tachycardia and in suppressing premature ventricular complexes (PVCs). It is less effective in the treatment of refractory ventricular tachycardia. Concurrent administration of digoxin, warfarin, or metoprolol with propafenone has been shown to increase the serum concentrations of those three drugs, while cimetidine slightly increases the propafenone concentrations. Additive pharmacologic effect can occur when lidocaine, procainamide, and quinidine are combined with propafenone. Overall, 21% to 32% of patients experience adverse effects, with 3% to 7% of these serious enough to warrant discontinuing therapy. The most common adverse effects are dizziness or lightheadedness, metallic taste, and nausea and vomiting; the most serious adverse effects are proarrhythmic events. The initial dosage of the treatment of ventricular arrhythmias is 150 mg every eight hours for both rapid and poor metabolizers; increases should be made gradually over a three- to four-day period. For maintenance therapy; 450 to 900 mg/day orally in three or four divided doses has been shown to be effective. Propafenone is an effective and generally well tolerated antiarrhythmic agent for the treatment of PVCs and for initial treatment of ventricular tachycardia.