Propafenone Hydrochloride

• Ventricular Arrhythmias:
  Treatment of life-threatening ventricular arrhythmias such as ventricular tachycardia and premature ventricular contractions (PVCs).
• Supraventricular Arrhythmias:
  Management of paroxysmal supraventricular tachycardia (PSVT), including atrial fibrillation and atrial flutter.
• Maintenance of Sinus Rhythm:
  Prevention of recurrent atrial fibrillation or flutter following conversion to sinus rhythm.
• Off-label Uses:
  Occasionally used for other refractory arrhythmias as determined by a cardiologist.

Route: Oral (tablets); intravenous form is rarely used and limited to hospital settings.

Adults:

• Initial oral dose: 150 mg every 8 hours.
• Dose may be increased after 3 days to 225 mg every 8 hours if tolerated and needed.
• Maximum dose: 300 mg every 8 hours.
• Dosage adjustment should be guided by clinical response and side effects.

Elderly:

• Start with lower doses due to decreased metabolism and increased sensitivity.
• Careful monitoring recommended.

Hepatic Impairment:

• Use with caution; dose adjustment necessary due to reduced metabolism.
• Start at half the usual dose and titrate carefully.

Renal Impairment:

• No significant dosage adjustment generally required but monitor for toxicity.

Administration Notes:

• Tablets should be swallowed whole with water, with or without food.
• Consistency in administration relative to meals is recommended to avoid fluctuations in absorption.

Propafenone hydrochloride is a Class IC antiarrhythmic agent that exerts its effects primarily by blocking the fast sodium channels in cardiac myocytes. This action slows phase 0 depolarization of the cardiac action potential, resulting in decreased conduction velocity throughout the myocardium, particularly in the His-Purkinje system and ventricular myocardium. It also exhibits some beta-adrenergic blocking activity, contributing to decreased heart rate and contractility. The combined effect suppresses abnormal automaticity and reentrant arrhythmias, restoring and maintaining normal cardiac rhythm.

• Absorption: Well absorbed orally with bioavailability of approximately 4-30% due to first-pass metabolism. Peak plasma levels achieved within 3-6 hours.
• Distribution: Widely distributed, highly protein-bound (~90%).
• Metabolism: Extensively metabolized in the liver primarily via CYP2D6, with minor contributions from CYP1A2 and CYP3A4 isoenzymes.
• Active Metabolites: 5-hydroxypropafenone is an active metabolite contributing to antiarrhythmic activity, especially in extensive metabolizers.
• Elimination: Excreted primarily in urine and feces. Half-life varies from 3 to 10 hours depending on CYP2D6 metabolism status (poor vs extensive metabolizers).

• Pregnancy: Category C. Animal studies have shown adverse fetal effects at high doses. Use only if potential benefit justifies risk to fetus.
• Lactation: Excreted in breast milk in small amounts. Caution advised; breastfeeding not recommended unless benefits outweigh risks.

• Class: Antiarrhythmic Agent
• Subclass: Class IC sodium channel blocker

• Known hypersensitivity to propafenone or any excipients.
• Structural heart disease with significant left ventricular dysfunction (e.g., recent myocardial infarction with reduced ejection fraction).
• Cardiogenic shock or severe heart failure.
• Second- or third-degree atrioventricular (AV) block without a pacemaker.
• Sick sinus syndrome without pacemaker.
• Bradycardia or prolonged QT interval.
• Concomitant use with other Class I antiarrhythmics (e.g., flecainide) or drugs that may cause torsades de pointes.

• Use with caution in patients with ischemic heart disease, heart failure, or conduction disturbances.
• May worsen arrhythmias (proarrhythmic effect), especially in structural heart disease.
• Monitor ECG and plasma levels during therapy.
• Risk of bronchospasm in patients with reactive airway disease due to beta-blocking properties.
• Avoid abrupt discontinuation to prevent arrhythmia rebound.
• Monitor liver function during prolonged therapy.

• Common:
• Cardiovascular: Palpitations, bradycardia, hypotension, dizziness.
• CNS: Headache, fatigue, tremor, taste disturbances (metallic taste).
• GI: Nausea, constipation.
• Serious:
• Life-threatening arrhythmias, including ventricular tachycardia and fibrillation.
• Heart block or severe bradyarrhythmias.
• Allergic reactions (rash, angioedema).
• Hepatotoxicity (rare).
• Bronchospasm.
• Rare:
• Lupus-like syndrome.
• Agranulocytosis or blood dyscrasias.

• CYP2D6 substrates and inhibitors: May alter propafenone metabolism (e.g., fluoxetine, paroxetine increase levels).
• Other antiarrhythmics: Increased risk of additive cardiac effects and arrhythmias.
• Beta-blockers and calcium channel blockers: May enhance negative chronotropic and inotropic effects.
• Warfarin: Propafenone may increase anticoagulant effects; monitor INR closely.
• Digoxin: May increase digoxin levels; monitor for toxicity.
• CYP3A4 and CYP1A2 modulators: Can influence propafenone metabolism and plasma concentrations.

• Emphasis on careful patient selection, avoiding use in structural heart disease due to increased mortality risk.
• Recommendation for therapeutic drug monitoring in patients with variable metabolism or at risk of toxicity.
• Updated warnings on proarrhythmic potential and need for close ECG surveillance during initiation and dose changes.
• Not recommended as first-line in heart failure or post-myocardial infarction patients per current cardiology guidelines.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in tightly closed container.
• Keep out of reach of children.