Propafenone

Propafenone hydrochloride extended-release capsules are indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. Usage Considerations: • The use of propafenone hydrochloride extended-release capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use propafenone hydrochloride extended-release capsules to control ventricular rate during AF. • Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate. Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended.

Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. Studies in anesthetized dogs and isolated organ preparations show that propafenone has beta-sympatholytic activity at about 1/50 the potency of propranolol.

Propafenone hydrochloride extended-release capsules can be taken with or without food. Do not crush or further divide the contents of the capsule. The dose of propafenone hydrochloride extended-release capsules must be individually titrated on the basis of response and tolerance. Initiate therapy with propafenone hydrochloride extended-release capsules 225 mg given every 12 hours. Dosage may be increased at a minimum of 5-day intervals to 325 mg given every 12 hours. If additional therapeutic effect is needed, the dose of propafenone hydrochloride extended-release capsules may be increased to 425 mg given every 12 hours. In patients with hepatic impairment or those with significant widening of the QRS complex or second- or third-degree AV block, consider reducing the dose.

Propafenone hydrochloride extended-release capsules are contraindicated in the following circumstances: • Heart failure • Cardiogenic shock • Sinoatrial, atrioventricular and intraventricular disorders of impulse generation or conduction (e.g., sick sinus node syndrome, AV block) in the absence of an artificial pacemaker • Known Brugada Syndrome • Bradycardia • Marked hypotension • Bronchospastic disorders or severe obstructive pulmonary disease • Marked electrolyte imbalance • Heart failure. • Cardiogenic shock. • Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation and/or conduction in the absence of pacemaker. • Known Brugada Syndrome. • Bradycardia.

Boxed warning (mortality •): In the National Heart, Lung, and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind trial in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than 6 days but less than 2 years previously, an increased rate of death or reversed cardiac arrest rate (7.7%, 56/730) was seen in patients treated with encainide or flecainide (Class IC antiarrhythmics) compared with that seen in patients assigned to placebo (3 %, 22/725). • May cause new or worsened arrhythmias. Evaluate patients via ECG prior to and during therapy. • Propafenone hydrochloride extended-release capsules may unmask Brugada or Brugada-like Syndrome. Evaluate patients via ECG after initiation of therapy. • Avoid use with other antiarrhythmic agents or drugs that prolong the QT interval.

The most commonly reported adverse events with propafenone (greater than 5% and greater than placebo) excluding those not reasonably associated with the use of the drug included the following: dizziness, palpitations, chest pain, dyspnea, taste disturbance, nausea, fatigue, anxiety, constipation, upper respiratory tract infection, edema, and influenza.

• Inhibitors of CYP2D6, 1A2, and 3A4 may increase propafenone levels which may lead to cardiac arrhythmias. Simultaneous use with both a CYP3A4 and CYP2D6 inhibitor (or in patients with CYP2D6 deficiency) should be avoided. • Propafenone may increase digoxin or warfarin levels. • Orlistat may reduce propafenone concentrations. Abrupt cessation of orlistat in patients stable on propafenone hydrochloride extended-release capsules has resulted in convulsions, atrioventricular block, and circulatory failure. • Concomitant use of lidocaine may increase central nervous system side effects.

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F).