PROPAFENONE HYDROCHLORIDE

Absorption/Bioavailability Propafenone hydrochloride is nearly completely absorbed after oral administration with peak plasma levels occurring approximately 3.5 hours after administration in most individuals. Propafenone exhibits extensive saturable presystemic biotransformation (first-pass effect) resulting in a dose-dependent and dosage-form-dependent absolute bioavailability; e.g., a 150 mg tablet had absolute bioavailability of 3.4%, while a 300 mg tablet had absolute bioavailability of 10.6...

In 2 randomized, crossover, placebo-controlled, double-blind trials of 60 to 90 days’ duration in subjects with PAF or PSVT, propafenone reduced the rate of both arrhythmias, as shown in Table 3. Table 3. Reduction of Arrhythmias in Subjects with Paroxysmal Atrial Fibrillation/ Flutter or Paroxysmal Supraventricular Tachycardia

Trial 1

Trial 2Propafenone Placebo Propafenone Placebo PAF n = 30 n = 30 n = 9 n = 9 Percent attack free 53% 13% 67% 22% Median time to first recurrence >98 days 8 days 62 days 5 days PSVT n = 45 n = 45 n = 15 n = 15 Percent attack free 47% 16% 38% 7% Median time to fi...

The most commonly reported adverse events with propafenone (greater than 5%) included: unusual taste, nausea and/or vomiting, dizziness, constipation, headache, fatigue, first-degree AV block, and intraventricular conduction delay. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction r...

Propafenone hydrochloride tablets 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...

May cause new or worsened arrhythmias. Evaluate patients via ECG prior to and during therapy. (5.1) Propafenone hydrochloride may unmask Brugada or Brugada-like Syndrome. (4 , 5.2) Avoid use with other drugs that prolong the QT interval. (5.3) Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). (5.4) May provoke overt heart failure. (5.5) May cause dose-related first-degree AV block or other conduction disturbances. Only use in p...

7 DRUG INTERACTIONS Inhibitors of CYP2D6, 1A2, and 3A4 increase propafenone exposure. (7.1) Propafenone may increase digoxin or warfarin levels. (7.2 , 7.3) Orlistat may reduce propafenone exposure. Taper orlistat withdrawal. (7.4) Lidocaine may increase central nervous system side effects. (7.6) 7.1 CYP2D6 and CYP3A4 Inhibitors Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir...