Overview
11 DESCRIPTION Propafenone hydrochloride is an antiarrhythmic drug supplied in film-coated tablets of 150 mg, 225 mg and 300 mg for oral administration. Propafenone has some structural similarities to beta-blocking agents. Chemically, propafenone hydrochloride is 2’-[2-hydroxy-3-(propylamino)-propoxy]-3-phenylpropiophenone hydrochloride, with a molecular weight of 377.92.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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.
Indications
- 1 INDICATIONS AND USAGE Propafenone hydrochloride tablets are indicated to: prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. prolong the time to recurrence of paroxysmal supraventricular tachycardia (PSVT) associated with disabling symptoms in patients without structural heart disease. treat documented ventricular arrhythmias, such as sustained ventricular tachycardia that, in the judgment of the physician, are life-threatening. Initiate treatment in the hospital.
Common Doses
- 150 mg
- 450 mg
- 225 mg
- 675 mg
Dosage
2 DOSAGE AND ADMINISTRATION The dose of propafenone hydrochloride tablets must be individually titrated on the basis of response and tolerance. Initiate therapy with propafenone hydrochloride tablets 150 mg given every 8 hours (450 mg per day). Dosage may be increased at a minimum of 3- to 4- day intervals to 225 mg every 8 hours (675 mg per day). If additional therapeutic effect is needed, the dose of propafenone hydrochloride tablets may be increased to 300 mg every 8 hours (900 mg per day). The usefulness and safety of dosages exceeding 900 mg per day have not been established.
Black Box Warning
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 subjects 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 subjects treated with encainide or flecainide (Class IC antiarrhythmics) compared with that seen in subjects assigned to placebo (3.0%; 22/725).
Contraindications
- 4 CONTRAINDICATIONS 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 pulmonary disease Marked electrolyte imbalance Heart failure (4) Cardiogenic shock (4) Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or...
Side Effects
- 6 ADVERSE REACTIONS 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 rates observed in the clinical trials of a drug cannot be directly compared with...
Interactions
- 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, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, grapefruit juice) can be expected to cause increased plasma levels of propafenone.