Propafenone (Monograph)

Brand name: Rythmol
Drug class: Class Ic Antiarrhythmics
VA class: CV300
Chemical name: 1-Propanone,1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-3- phenylpropan-1-one hydrochloride
Molecular formula: C₂₁H₂₇NO₃
CAS number: 34183-22-7

Medically reviewed by Drugs.com on Nov 4, 2024. Written by ASHP.

Introduction

Propafenone is a local anesthetic type Ic antiarrhythmic agent.¹ ³ ³⁸ ¹³⁴ ²⁸⁹

Uses for Propafenone

Supraventricular Tachyarrhythmias

Used (as conventional [immediate-release] tablets) to prolong the time to recurrence of symptomatic, disabling paroxysmal supraventricular tachycardia (PSVT) (e.g., AV nodal reentrant tachycardia or AV reentrant tachycardia [Wolff-Parkinson-White, WPW, syndrome]) and symptomatic, disabling paroxysmal atrial fibrillation/flutter (PAF) in patients without structural heart disease.¹ ³ ⁶⁷ ⁶⁸ ⁹⁰ ⁹¹ ⁹² ⁹³ ⁹⁴ ⁹⁹ ¹⁰¹ ¹⁰² ¹⁰⁵ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹ ¹¹⁰ ¹³² ¹³³ ¹⁷³ ¹⁸⁷ ²⁰⁶ ²¹¹

Used (as extended-release capsules) to prolong the time to recurrence of symptomatic PAF in patients without structural heart disease.²⁸⁹ Safety and efficacy of extended-release capsules not established in patients with exclusively PSVT or atrial flutter.²⁸⁹

One of several drugs that may be used for ongoing management of patients with PSVT who do not have structural or ischemic heart disease; generally reserved for patients in whom other therapies (e.g., catheter ablation, β-adrenergic blocking agents, diltiazem, verapamil) are ineffective or contraindicated.⁷⁰⁰

Comparably effective to quinidine, disopyramide, flecainide, procainamide, sotalol in preventing recurrences of PAF and maintaining sinus rhythm following successful cardioversion of atrial fibrillation.³ ⁶⁸ ⁸⁹ ¹²⁹ ¹³³ ¹⁸³ ²⁰⁰ ²⁰¹ ²⁰² ²⁰⁴ ²⁰⁵

Safety and efficacy not established in patients with chronic atrial fibrillation.¹ ²⁸⁹

Has been used for pharmacologic cardioversion of atrial fibrillation or flutter^{† [off-label]}.¹⁵ ⁶⁸ ⁸⁸ ⁸⁹ ⁹⁰ ¹⁰¹ ¹⁰³ ¹⁰⁴ ¹⁰⁹ ¹¹⁰ ¹¹¹ ¹⁹⁵ ¹⁹⁶ ¹⁹⁷ ¹⁹⁸ ¹⁹⁹ ²⁰⁷ ²⁰⁸ ²¹¹ ²⁷² ⁷⁰¹

May be used for ongoing management of other supraventricular tachycardias (SVTs) (e.g., focal atrial tachycardia^{† [off-label]}, junctional tachycardia^{† [off-label]}).⁷⁰⁰

Because of risk of proarrhythmia, do not use in patients with structural heart disease or ischemic heart disease.⁷⁰⁰

Ventricular Arrhythmias

As conventional (immediate-release) tablets, suppresses and prevents recurrence of documented life-threatening ventricular arrhythmias (e.g., sustained VT, VF).¹ ³ (See Mortality under Cautions.)

Propafenone Dosage and Administration

General

Individualize dosage according to individual requirements, response, tolerance, general condition, and cardiovascular status.¹ ² ³ ⁹ ¹⁵ ²⁸ ⁴⁷ ⁶⁸
Initiate therapy (conventional [immediate-release] tablets) for life-threatening ventricular arrhythmias in a hospital.¹ ²⁷³
Clinical and ECG evaluation (e.g., Holter monitoring) is recommended during propafenone therapy.¹ ³ ²⁸⁹

Administration

Administer orally.

Has been administered IV^{† [off-label]},³ ¹⁷ ³¹ ⁷⁶ ⁸⁸ ⁸⁹ ⁹⁰ ⁹⁵ ⁹⁶ ⁹⁷ ⁹⁸ ¹⁰⁰ ¹⁰² ¹⁰⁴ ¹⁰⁶ ¹¹⁰ ¹¹⁹ ¹²² ¹³³ ¹⁸³ but parenteral dosage form not commercially available in US.

Oral Administration

Administer conventional (immediate-release) tablets in a consistent manner relative to food intake.⁶ ⁹ ¹²⁸ ²⁵⁶ ²⁷² ²⁷³

Administer conventional (immediate-release) tablets in 3 equally divided doses daily at 8-hour intervals.¹

Administer extended-release capsules in equally divided doses every 12 hours without regard to meals.²⁸⁹

Swallow extended-release capsules whole; do not crush.²⁸⁹

Avoid grapefruit juice.²⁷² ²⁷³ (See Drugs, Foods, and Herbal Supplements under Interactions.)

Dosage

Adjust dosage carefully according to individual requirements and response, patient tolerance, and the general condition and cardiovascular status of the patient.¹ ² ³ ⁹ ¹⁵ ²⁸ ⁴⁷ ⁶⁸ ²⁸⁹

Consider dosage reduction in patients who develop excessive prolongation of the PR interval, excessive QRS widening, or second- or third-degree AV block.¹ ² ³ ¹⁵ ⁹⁰

Usually do not use oral loading doses (conventional [immediate-release] tablets) since acute toxicity may occur.³ ⁶ ²⁷² ²⁷³ However, oral loading doses (e.g., 450–750 mg as conventional [immediate-release] tablets) have been used with apparent safety for conversion of recent-onset atrial fibrillation to normal sinus rhythm^{† [off-label]} in individuals without heart failure.⁶⁸ ⁸⁹ ⁹⁰ ¹⁰¹ ¹⁰⁹ ¹⁶⁰ ¹⁹⁵ ¹⁹⁶ ²⁰⁸ ²⁷²

Pediatric Patients

Supraventricular Arrhythmias

Oral (conventional [immediate-release] tablets)

Some clinicians suggest maximum daily dosage 600 mg/m².²⁷²

Adults

Paroxysmal Atrial Fibrillation/Flutter and Paroxysmal Supraventricular Tachyarrhythmias

Oral (conventional [immediate-release] tablets)

Initially, 150 mg every 8 hours.¹ ² ⁶⁸

Increase dosage after 3–4 days to 225 mg 3 times daily (every 8 hours) if necessary.¹ ⁶⁸ ⁹⁰

If desired therapeutic response is not attained after an additional 3–4 days, increase dosage to 300 mg 3 times daily (every 8 hours).¹ ⁶⁸ ⁹⁰

Oral (extended-release capsules)

Initially, 225 mg every 12 hours.²⁸⁹

Increase dosage after ≥5 days to 325 mg every 12 hours if necessary.²⁸⁹

If desired therapeutic response is not attained after an additional 5 days, increase dosage to 425 mg every 12 hours.²⁸⁹

If a dose is missed, only administer the next scheduled dose; do not double next dose.²⁸⁹

When switching from conventional (immediate-release) tablets to extended-release capsules, the dosage conversion ratio is not a 1:1 substitution (e.g., a patient who currently is receiving 150 mg every 8 hours of conventional (immediate-release) tablets may be switched to 325 mg of extended-release capsules every 12 hours).²⁸⁹ ³⁰⁸

Conversion of Atrial Fibrillation to Normal Sinus Rhythm†

Oral (conventional [immediate-release] tablets)

150–600 mg, as a single dose.¹⁵⁸ ²¹¹

IV†

2 mg/kg (over 10 minutes) as a single dose.¹⁵⁸ ²¹¹

Self-administration for Conversion of PAF†

Oral (conventional [immediate-release] tablets)

Adults weighing 70 kg or more: May use a single oral loading dose of 600 mg 5 minutes after noting the onset of palpitations.²⁹⁰ ³⁰⁹

Adults weighing < 70 kg: May use a single oral loading dose of 450 mg 5 minutes after noting the onset of palpitations.²⁹⁰ ³⁰⁹

Do not take more than a single oral dose during a 24-hour period.²⁹⁰

Ventricular Arrhythmias

Oral (conventional [immediate-release] tablets)

Initially, 150 mg every 8 hours.¹ ² ⁶⁸

Increase dosage after 3–4 days to 225 mg 3 times daily if necessary.¹ ⁶⁸ ⁹⁰

If desired therapeutic response is not attained after an additional 3–4 days, increase dosage to 300 mg 3 times daily.¹ ⁶⁸ ⁹⁰

Prescribing Limits

Pediatric Patients

Supraventricular Arrhythmias

Oral (conventional [immediate-release] tablets)

Some clinicians suggest maximum daily dosage of 600 mg/m².²⁷²

Adults

Supraventricular Arrhythmias

Oral (conventional [immediate-release] tablets)

Maximum daily dosage is 900 mg.¹ ⁹ ⁹⁰ ²⁷² ²⁷³

Life-threatening Ventricular Arrhythmias

Oral (conventional [immediate-release] tablets)

Maximum daily dosage is 900 mg.¹ ⁹ ⁹⁰ ²⁷² ²⁷³

Special Populations

Hepatic Impairment

When conventional (immediate-release) tablets are used, reduce dosage by approximately 70–80%; monitor patients for signs of toxicity, including hypotension, somnolence, bradycardia, conduction disturbances, seizures, and/or ventricular arrhythmias.¹ ¹¹⁵ ¹⁹³

Geriatric Patients and Those with Myocardial Damage

During initiation of therapy (conventional [immediate-release] tablets), gradual dosage escalation should be performed in geriatric patients and those with marked previous myocardial ischemia.¹ ³

Cautions for Propafenone

Contraindications

Patients with uncontrolled CHF (conventional [immediate-release] tablets),¹ CHF (extended-release capsules).²⁸⁹
Cardiogenic shock.¹ ³ ²⁸⁹
Sinoatrial, AV, or intraventricular disorders of impulse generation and/or conduction (e.g., sick sinus node syndrome, AV block) unless an artificial pacemaker is present.¹ ³ ⁶ ²³⁴ ²⁸⁹
Bradycardia.¹ ³ ²⁸⁹
Severe hypotension.¹ ³ ²⁸⁹
Bronchospastic disorders.¹ ²⁸⁹
Marked electrolyte imbalance.¹ ³ ²⁸⁹
Known hypersensitivity to propafenone.¹ ²⁸⁹

Warnings/Precautions

Warnings

Mortality

In CAST study, excessive rate of mortality and nonfatal cardiac arrest reported in patients with asymptomatic or mildly symptomatic non-life-threatening ventricular arrhythmias and recent MI (>6 days but <2 years previously) who were receiving encainide or flecainide compared with placebo.¹ ¹¹⁶ ¹¹⁷ ¹⁴⁹ ¹⁵⁵ ²³⁴ ²³⁵ ²⁸⁹ The applicability of these results to other populations (e.g., those without recent MI) or to other antiarrhythmic drugs is uncertain.¹ ⁶ ⁴⁸ ⁶² ¹¹⁸ ¹⁶⁸ ²³⁴ ²³⁵

Limit use of propafenone or other class I agents in patients with ventricular arrhythmias to those with life-threatening arrhythmias;¹ ¹¹⁶ ¹¹⁷ use in patients with less severe ventricular arrhythmias, even when symptomatic, is not recommended.¹

Arrhythmogenic and Cardiac Conduction Effects

Potential for new and/or more severe arrhythmias,¹ ² ³ ⁴ ⁶ ⁹ ¹⁵ ¹⁶ ¹⁷ ¹⁸ ⁴⁷ ⁵⁸ ⁶⁷ ⁶⁸ ⁷⁵ ¹¹³ ¹¹⁶ ¹⁶⁸ ²³⁰ ²³² ²³³ ²³⁴ ²³⁵ especially in those with CHF (NYHA class III or IV) or myocardial ischemia.²⁸⁹

Risk of clinically important conduction disturbances;¹ ⁶ ⁷⁵ ¹³⁶ ¹⁵¹ degree of lengthening of PR and QRS intervals may increase progressively with increasing dosage and plasma propafenone concentrations.¹ ² ⁴⁷ ²³³ ²⁸⁹ ¹ ² ⁶ ⁹ ⁴⁷ ⁶⁸ ¹⁶⁸ ²³³ ²⁸⁹

Reduce dosage or discontinue the drug if 2nd- or 3rd-degree AV block occurs.¹ (See Contraindications under Cautions.)

Evaluate clinical status and ECG prior to and during propafenone therapy to monitor for appearance of arrhythmias and to determine the need for continued therapy.¹ ² ¹⁶⁸

Monitor patients with permanent artificial pacemakers and, if necessary, reprogram pacemakers.¹ ² ³ ²²⁵ ²²⁹ ²⁸⁹

Cardiovascular Effects

Potential for new or worsened CHF, particularly in patients with preexisting heart failure or ejection fraction <30%.¹ ² ³ ⁴ ⁹ ¹³ ¹⁷ ⁴⁷ ⁶⁸ ⁷⁵ ¹¹⁷ ²⁸⁹

Use with caution (conventional [immediate-release] tablets) in patients with a history of CHF or myocardial dysfunction.¹ ¹¹⁷ ¹⁶⁸ ²³⁵ ²³⁶

Discontinue therapy if CHF worsens (unless caused by the cardiac arrhythmia); fully compensate CHF before therapy is reinitiated.¹

Hematologic Effects

Possible reversible granulocytopenia³ ⁴⁷ and agranulocytosis.¹ ⁴⁷

Carefully evaluate patients in whom unexplained fever and/or decreased WBC counts occur (especially during the initial 3 months of therapy).¹ ²⁸⁹ WBC counts generally return to normal within 2 weeks following discontinuance.¹ ²⁸⁹

Bronchospastic Disease

Possible inhibition of bronchodilation produced by endogenous catecholamines; use generally not recommended in patients with asthma/bronchospastic disease or nonallergic bronchospastic disease (e.g., chronic bronchitis, emphysema).¹ ³ ¹⁵ ⁴⁰ ⁶⁷ ⁶⁸ ¹⁷³ ²¹⁵ ²⁸⁹ (See Contraindications under Cautions.)

General Precautions

Hepatic Impairment

Extensively metabolized in liver; use with caution in those with hepatic impairment.¹ ³ ⁸ ¹¹ ¹⁵ ³³ ⁶⁸ ¹⁷⁸ ²⁸⁹

Renal Impairment

Several metabolites excreted by kidneys; use with caution in those with renal impairment.¹ ¹³ ²⁸⁹

Antinuclear Antibodies.

Possible positive antinuclear antibody (ANA) titers.¹ ²⁸⁹

Monitor carefully patients who develop an abnormal ANA test following initiation of therapy; consider discontinuation of therapy if titers remain elevated or increase further.¹ ²⁸⁹

Impaired Spermatogenesis

Transient, reversible decreases (within normal range) in sperm count may occur.¹ ²⁸⁹

Myasthenia Gravis

Possible exacerbation of myasthenia gravis.¹ ⁵² ²⁸⁹ Avoid use in patients with this condition.³

Specific Populations

Pregnancy

Category C.¹ ²⁸⁹

Lactation

Distributed into milk.³ ²⁸⁹ Caution if used in nursing women.²⁸⁹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹ ²⁷³ ²⁸⁹

Has been used successfully and without unusual adverse effects in a limited number of infants and children^† for the management of various refractory supraventricular (e.g., PSVT, junctional ectopic tachycardia, atrial fibrillation or flutter) and ventricular (e.g., VPCs, VT) arrhythmias.³ ⁶⁸ ¹⁴⁶ ²¹² ²¹³ ²¹⁴ ²¹⁶ ²¹⁷ ²¹⁸ ²²⁰ ²⁷²

Geriatric Use

Conventional (immediate-release) tablets: Insufficient experience to determine whether geriatric patients ≥65 years of age respond differently than younger adults.¹ Select dosage with caution; start at the lower end of dosing range due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.¹

Extended-release capsules: No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.²⁸⁹

Hepatic Impairment

Extensively metabolized in liver; use with caution.¹ ³ ⁸ ¹¹ ¹⁵ ³³ ⁶⁸ ¹⁷⁸ ²⁸⁹ Careful monitoring for excessive pharmacological effects recommended.¹ Reduce dosage.¹ ³ ⁸ ¹¹ ¹⁵ ³³ ⁶⁸ ¹⁷⁸ ²⁸⁹ (See Special Populations under Dosage and Administration.)

Renal Impairment

Use with caution.¹ Careful monitoring for excessive pharmacological effects recommended.¹

Common Adverse Effects

Conventional (immediate-release) tablets: Unusual taste, nausea and/or vomiting, dizziness, constipation, headache, fatigue, blurred vision, and weakness.¹ First-degree AV block and intraventricular conduction delay in patients with ventricular arrhythmia.¹

Extended-release capsules: Constipation, diarrhea, dry mouth, nausea, vomiting, unusual taste, fatigue, weakness, dizziness, headache, somnolence, anxiety, dyspnea, ecchymosis, upper respiratory infection, abnormalities in liver function tests (e.g., increased serum concentrations of alkaline phosphatase), hematuria.²⁸⁹

Drug Interactions

Metabolized by CYP2D6 and to a lesser extent by CYP1A2, CYP3A4.¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹

Inhibits CYP2D6.¹ ²⁸⁹

Drugs and Foods Affecting Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP2D6, CYP1A2, or CYP3A4 with possible alteration in metabolism of propafenone and/or other drugs.¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹ Monitor patients.¹

Drugs Metabolized by p-Glycoprotein Transporter

Effect of propafenone on the p-glycoprotein transport system not evaluated.¹ ²⁸⁹

Drugs Affecting QT Interval

Do not use with drugs that prolong the QT interval.²⁸⁹

Antiarrhythmic Agents

Use extreme caution when propafenone is administered with other antiarrhythmic agents.³ ⁶⁸ Reserve concomitant use for management of life-threatening arrhythmias unresponsive to propafenone monotherapy.³ ⁶⁸ Do not use propafenone (extended-release capsules) with class Ia or III antiarrhythmic agents.²⁸⁹

Specific Drugs and Foods

Drug or Food	Interaction	Comments
Amiodarone	Possible increased incidence of cardiovascular effects¹ ¹³ ²⁸⁷ ²⁸⁹ Increased propafenone concentrations¹ ²⁸⁹	Concomitant use not recommended ¹ ²⁸⁹
β-adrenergic blocking agents (e.g., metoprolol, propranolol)	Increased β-adrenergic blocking agent concentrations and terminal elimination half-life¹ ²⁴⁶ ²⁴⁷ ²⁸⁹	Use concomitantly with caution; consider β-adrenergic blocking agent dosage reduction¹ ⁶ ⁹ ¹³ ²⁴⁷ ²⁸⁹
Calcium channel-blocking agents	No evidence of clinically important adverse interactions¹ ²⁸⁹
Cimetidine	Increased propafenone steady-state plasma concentrations¹ ²⁸⁹
Cyclosporine	Increased cyclosporine concentrations¹ ²⁵⁰ ²⁸⁹
Desipramine	Increased propafenone concentrations¹ ²⁸⁹ Increased desipramine serum concentrations¹	Use concomitantly with caution; reduce propafenone hydrochloride dosage¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹ Consider desipramine dosage reduction¹
Digoxin	Increased serum or plasma digoxin concentrations¹ ³ ⁹ ⁸⁵ ¹²⁴ ¹²⁵ ²⁴⁵ ²⁷⁹ ²⁸⁰ ²⁸¹ ²⁸² ²⁸³ ²⁸⁹	Carefully monitor serum digoxin concentrations and adjust digoxin dosage ¹ ³ ⁹ ⁸⁵ ¹²⁴ ¹²⁵ ²⁴⁵ ²⁸³ ²⁸⁹
Diuretics	No evidence of clinically important adverse interactions¹ ²⁸⁹
Erythromycin	Increased propafenone concentrations¹ ²⁸⁹ ¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹	Use concomitantly with caution; reduce propafenone hydrochloride dosage¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹
Fluoxetine	In extensive-metabolizer phenotypes, increased peak plasma concentrations and AUC of propafenone¹ ²⁸⁹
Grapefruit juice	Possible increased plasma concentrations of unchanged propafenone and potential adverse effects¹ ²⁵⁷ ²⁵⁸ ²⁵⁹ ²⁶⁰ ²⁶¹ ²⁶² ²⁸⁹	Avoid concomitant use²⁷² ²⁷³
Haloperidol	Increased haloperidol concentrations¹ ²⁸⁹	Use concomitantly with caution; consider haloperidol dosage reduction¹ ²⁸⁹
Imipramine	Increased imipramine concentrations¹ ²⁸⁹	Use concomitantly with caution; consider imipramine dosage reduction¹ ²⁸⁹
Ketoconazole	Increased propafenone concentrations¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹	Use concomitantly with caution; reduce propafenone hydrochloride dosage¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹
Lidocaine	Possible pharmacologic interaction (additive or antagonistic cardiac effects and additive toxicity) ¹ ² ⁹ ¹³ ¹²² ²⁸⁹
Orlistat	Possible limited absorption of propafenone¹ ²⁸⁹ Possibility of severe adverse effects with abrupt discontinuance of orlistat¹ ²⁸⁹
Paroxetine	Increased propafenone concentrations¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹	Use concomitantly with caution; reduce propafenone hydrochloride dosage¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹
Phenobarbital	Decreased plasma propafenone concentrations³
Quinidine	Increased plasma propafenone concentrations¹ ³ ¹²³ ²⁸⁹	Concomitant use not recommended ¹ ²⁸⁹
Rifampin	Increased metabolism of propafenone resulting in decreased plasma propafenone concentrations and antiarrhythmic activity¹
Ritonavir	Increased propafenone concentrations¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹	Use concomitantly with caution; reduce propafenone hydrochloride dosage¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹
Saquinavir	Increased propafenone concentrations¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹	Use concomitantly with caution; reduce propafenone hydrochloride dosage¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹
Sertraline	Increased propafenone concentrations¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹	Use concomitantly with caution; reduce propafenone hydrochloride dosage¹ ¹³¹ ¹⁹⁰ ²⁸⁵ ²⁸⁶ ²⁸⁹
Theophylline	Increased serum theophylline concentrations and toxicity¹ ²⁸⁹
Venlafaxine	Increased venlafaxine concentrations¹ ²⁸⁹	Use concomitantly with caution; consider venlafaxine dosage reduction¹ ²⁸⁹
Warfarin	Increased plasma warfarin concentrations and corresponding PTs¹ ³ ⁶ ⁹ ¹³ ¹⁵ ²⁴⁸ ²⁸⁹	Monitor PTs or INRs;²⁷⁵ adjust warfarin dosage ¹ ³ ⁹ ¹³ ²⁴⁸ ²⁸⁹

Propafenone Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed following oral administration of conventional (immediate-release) tablets.¹ ³ ¹⁵ ¹⁷ ³³ ⁴⁰ ⁶⁷ ⁶⁸ ¹³³ ¹³⁶

Absolute bioavailability of conventional (immediate-release) tablets is 5–50%.³³ ¹⁷⁴ ¹⁸⁰

Bioavailability of 325-mg extended-release capsules (given twice daily) similar to 150-mg conventional (immediate-release) tablets (given 3 times daily).²⁸⁹

Food

Food does not appear to affect bioavailability of conventional (immediate-release) tablets or extended-release capsules during multiple-dose administration.² ²⁸⁹

Special Populations

In patients with marked hepatic impairment, bioavailability of conventional (immediate-release) tablets is about 60–70%.¹ ² ¹⁷⁸ ²⁸⁹

Distribution

Extent

Rapidly distributed into lung, liver, and heart tissue.³ ⁴ ¹⁵

Propafenone crosses the placenta and is distributed into milk.³ ⁶⁴ ⁷²

Plasma or Serum Protein Binding

81–97% (mainly α₁ acid glycoprotein).³ ¹³⁸ ¹⁸⁷ ¹⁸⁸ ²⁸⁹

Special Populations

In patients with severe hepatic dysfunction, approximately 88% of propafenone is bound to plasma proteins.²⁸⁹

Elimination

Metabolism

Extensively metabolized by first-pass metabolism (hydroxylation) in the liver,¹ ³³ ¹³² ¹³³ ¹³⁶ via CYP2D6 to an active metabolite (5-hydroxypropafenone [5-OHP])¹ ¹³¹ ¹⁹⁰ ²⁸⁹ and dealkylation via CYP1A2 and CYP3A4 to another active metabolite (N-depropylpropafenone [NDPP]).¹ ¹³¹ ²⁸⁹

Elimination Route

Eliminated principally in feces via biliary excretion as metabolites and in urine or feces as unchanged drug (<1%).² ³ ⁴ ³³ ⁶⁷ ⁶⁸ ¹³⁶

Half-life

Immediate-release tablets: Averages 1–3 hours (range: 2–10 hours).¹ ² ⁴ ⁶ ⁷ ¹⁰ ¹¹ ¹² ¹⁴ ¹⁵ ¹⁶ ²⁸ ³³ ³⁷ ³⁹ ⁶⁷ ⁶⁸ ⁷¹ ¹²⁹ ¹³³ ¹³⁸ ¹⁸¹ ¹⁸⁷

Special Populations

In patients with poor metabolizer phenotypes (approximately 5–10% of Caucasians), propafenone is metabolized principally via CYP3A4 and CYP1A2;¹ ¹³¹ CYP2D6 is subject to genetic polymorphism.¹ ¹³¹ ¹⁹⁰

Extensive metabolizers convert propafenone rapidly into 5-OHP and NDPP,¹ ¹⁵ ³³ ³⁷ ⁴¹ ⁶⁸ ⁷⁰ ¹²⁹ ¹³⁰ ¹³¹ ¹³⁶ ¹⁸⁹ ¹⁹⁰ ²⁸⁹ while poor metabolizers convert it slowly to NDPP and 5-OHP usually not detectable.¹ ³³ ³⁷ ¹⁸⁴ ¹⁸⁶ ²⁸⁹

Poor metabolizers have increased plasma propafenone concentrations relative to individuals with the extensive-metabolizer phenotype³ ¹³ ¹⁵ ³³ ⁴⁰ ⁶⁷ ⁶⁹ ¹³⁰ and are more likely to experience β-blocking and adverse effects of the drug.¹³ ³⁶ ³⁹ ¹²⁹

In poor metabolizers, plasma elimination half-life and steady-state half-life average about 8-13 (range: 10–32 hours)¹ ² ³ ⁴ ⁶ ¹⁰ ¹⁶ ³³ ³⁷ ³⁹ ⁴⁰ ⁶⁸ ¹³³ and 17 hours, respectively; decreased clearance of the drug observed.³³ ⁶⁷ ¹⁷⁵

In patients with moderate to severe hepatic impairment, half-life is about 9 hours.¹ ² ³ ⁴ ⁶ ¹⁵ ³³ ¹⁷⁸

Stability

Storage

Oral

Conventional (immediate-release) Tablets

Tight, light-resistant containers at 25°C (may be exposed to 15-30°C).¹ ² ⁶⁵ ⁶⁶

Extended-release Capsules

Tight containers at 25°C (may be exposed to 15-30°C).²⁸⁹

Actions

Membrane-stabilizing antiarrhythmic agent; exhibits local anesthetic effects.³ ⁴ ¹⁷ ⁶² ⁶⁷ ²⁸⁹
Combines with fast sodium channels within the myocardium and inhibits rapid sodium influx, which decreases the maximal rate of depolarization of phase 0 of the action potential.¹ ² ³ ⁴ ⁷ ⁹ ¹⁰ ¹² ¹⁴ ¹⁵ ²² ²⁸ ³³ ³⁸ ³⁹ ⁴⁵ ⁵⁶ ⁶² ⁶³ ⁶⁷ ⁶⁸ ¹²⁹ ¹³³ ¹³⁴ ¹⁸⁰ ²⁸⁹
Combines with fast sodium channels in both their active and inactive state³ ¹³⁵ and inhibits recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels.¹ ² ⁴ ⁶ ⁷ ¹⁰ ¹¹ ¹² ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁸ ¹⁹ ³³ ³⁸ ³⁹ ⁶² ⁶⁷ ⁶⁸ ⁹⁰ ¹³⁴ ¹³⁵ ¹⁶⁸ ¹⁸⁰
Exhibits electrophysiologic effects characteristic of class Ic antiarrhythmic agents, which slowly attach to and dissociate from transmembrane sodium channels.¹³⁹ ¹⁴⁰ ¹⁴¹ ¹⁶⁸
Produces dose-related decrease in intracardiac conduction within the His-Purkinje system, AV node, and intraventricular pathways.³ ⁴ ¹⁰ ¹⁷ ¹³⁴ ²⁸⁹
Produces dose-related increases in PR, QRS, AH, and HV intervals;¹ ³ ⁶ ⁷ ⁶² ⁹⁶ ¹²⁹ ¹³³ ¹³⁴ ¹⁸⁰ ²⁸⁹ at higher workload and heart rates, dose-related increases in QT interval occur.²⁸ ⁶⁷ ⁶⁸
Increases effective refractory period (ERP) during ventricular pacing.³ ²⁷ ⁶⁷
Exhibits a dose-dependent negative inotropic effect.¹ ³ ³⁹ ⁶⁸ ¹⁴⁴ ¹⁶⁸ ²⁷² ²⁸⁹
Exhibits β-adrenergic blocking activity.¹ ² ³ ⁴ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹ ¹² ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁸ ²² ²⁴ ²⁵ ²⁶ ²⁷ ³³ ³⁶ ³⁷ ³⁸ ³⁹ ⁴² ⁴⁵ ⁴⁶ ⁴⁷ ⁵⁶ ⁶² ⁶³ ⁶⁷ ⁶⁸ ¹²⁹ ¹³³ ¹³⁷ ²⁸⁹

Importance of taking propafenone in a consistent manner relative to food.⁶ ⁹ ¹²⁸ ²⁵⁶ ²⁷² ²⁷³
Importance of not ingesting grapefruit juice concomitantly with propafenone.²⁷² ²⁷³
If a dose of extended-release capsules is missed, only administer the next scheduled dose; do not double next dose.²⁸⁹
Advise patients who self-administer conventional (immediate-release) tablets for conversion of paroxysmal atrial fibrillation to remain in a supine or sitting position until resolution of palpitations or for a period of ≥4 hours following the dose.²⁹⁰ ³⁰⁹ Importance of informing clinician if palpitations do not resolve within 6–8 hours, if new symptoms (e.g., dyspnea, presyncope, syncope) occur, or a marked increase in heart rate develops.²⁹⁰
Advise patients to promptly report fever, sore throat, chills, or any other manifestation of infection.¹ ³ ²⁸⁹
Importance of immediately informing clinician if excessive or prolonged diarrhea, sweating, vomiting, loss of appetite or thirst occurs.²⁸⁹ ²⁸⁹
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.¹ ²⁸⁹
Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹ ²⁹⁰
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Propafenone Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules, extended-release	225 mg	RythmolSR	Reliant
		325 mg	RythmolSR	Reliant
		425 mg	RythmolSR	Reliant
	Tablets, film-coated	150 mg*	Propafenone Hydrochloride Tablets
			Rythmol (scored)	Reliant
		225 mg*	Propafenone Hydrochloride Tablets
			Rythmol (scored)	Reliant
		300 mg*	Propafenone Hydrochloride Tablets
			Rythmol (scored)	Reliant

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Reliant Pharmaceuticals, Inc. Rythmol (propafenone hydrochloride) prescribing information. Liberty Corner, NJ; 2004 Sept.

2. Knoll Laboratories. Rythmol (propafenone hydrochloride) product monograph. Whippany, NJ; 1991 Jun.

3. Bryson HM, Palmer KJ, Langtry HD et al. Propafenone: a reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias. Drugs. 1993; 45:85-130. https://pubmed.ncbi.nlm.nih.gov/7680987

4. Harron DWG, Brogden RN. Propafenone: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias. Drugs. 1987; 34:617-47. https://pubmed.ncbi.nlm.nih.gov/3322781

5. Nestico PF, Morganroth J, Horowitz LN. New antiarrhythmic drugs. Drugs. 1988; 35:286-319. https://pubmed.ncbi.nlm.nih.gov/3286214

6. Funck-Brentano C, Kroemer HK, Lee JT et al. Propafenone. N Engl J Med. 1990; 322:518-25. https://pubmed.ncbi.nlm.nih.gov/2405273

7. Parker RB, McCollam PL, Bauman JL. Propafenone: a novel type Ic antiarrhythmic agent. DICP. 1989; 23:196-202. https://pubmed.ncbi.nlm.nih.gov/2655298

8. Anon. Propafenone for cardiac arrhythmias. Med Lett Drugs Ther. 1990; 32:37-8. https://pubmed.ncbi.nlm.nih.gov/2182990

9. Chow MSS, Lebsack C, Hilleman D. Propafenone: a new antiarrhythmic agent. Clin Pharm. 1988; 7:869-77. https://pubmed.ncbi.nlm.nih.gov/3061720

10. Friedman PL, Antman EM, Singh BN. Propafenone: a new class IC antiarrhythmic drug for the management of ventricular arrhythmias. Hosp Formul. 1988; 23:531-536, 542.

11. Anon. A review of propafenone. Hosp Pharm. 1990; 25:177-8.

12. Nestico PF. Propafenone: a new antiarrhythmic drug. Am Fam Physician. 1988; 38:235-8. https://pubmed.ncbi.nlm.nih.gov/3046275

13. Birgersdotter-Green U. Propafenone for cardiac arrhythmias. Am J Med Sci. 1992; 303:123-8. https://pubmed.ncbi.nlm.nih.gov/1539611

14. Brzozowski LA. Antiarrhythmic propafenone: improving patient outcomes. Dimen Crit Care Nurs. 1993; 12:116-22.

15. Shen EN. Propafenone: a promising new antiarrhythmic agent. Chest. 1990; 98:434-41. https://pubmed.ncbi.nlm.nih.gov/2198142

16. Somberg JC, Tepper D, Landau S. Propafenone: a new antiarrhythmic agent. Am Heart J. 1988; 115:1274-9. https://pubmed.ncbi.nlm.nih.gov/3287873

17. Hernandez M, Reder RF, Marinchak RA et al. Propafenone for malignant ventricular arrhythmia: an analysis of the literature. Am Heart J. 1991; 121:1178-84. https://pubmed.ncbi.nlm.nih.gov/2008842

18. Schlepper M. Propafenone, a review of its profile. Eur Heart J. 1987; 8(Suppl A):27-32. https://pubmed.ncbi.nlm.nih.gov/3556176

19. Harrison DC. Antiarrhythmic drug classification: new science and practical applications. Am J Cardiol. 1985; 56:185-7. https://pubmed.ncbi.nlm.nih.gov/2409789

20. Kowey PR, Stohler JL, Friehling TD et al. Propafenone in the treatment of patients with malignant ventricular tachyarrhythmias. Can J Cardiol. 1991; 7:175-80. https://pubmed.ncbi.nlm.nih.gov/2070286

21. Cueni L, Podrid PJ. Propafenone therapy in patients with serious ventricular arrhythmia—noninvasive evaluation of efficacy. J Electrophysiol. 1987; 1:548-60.

22. Budde T, Borggrefe M, Podczeck A et al. Acute and long-term efficacy of oral propafenone in patients with ventricular tachyarrhythmias. J Cardiovasc Pharmacol. 1991; 18:254-60. https://pubmed.ncbi.nlm.nih.gov/1717787

23. Geibel A, Meinertz T, Zehender M et al. Antiarrhythmic efficacy and tolerance of oral propafenone in patients with frequent ventricular arrhythmias: experience of a multicentre study. Eur Heart J. 1989; 10(Suppl E):81-7. https://pubmed.ncbi.nlm.nih.gov/2680506

24. Singh BN, Kaplinsky E, Kirsten E et al et al. Effects of propafenone on ventricular arrhythmias: double-blind, parallel, randomized, placebo-controlled dose-ranging study. Am Heart J. 1988; 116:1542-51. https://pubmed.ncbi.nlm.nih.gov/3057844

25. Hammill SC, Sorenson PB, Wood DL et al. Propafenone for the treatment of refractory complex ventricular ectopic activity. Mayo Clin Proc. 1986; 61:98-103. https://pubmed.ncbi.nlm.nih.gov/3945115

26. Dhin H, Baker BJ, de Soyza N et al. Sustained therapeutic efficacy and safety of oral propafenone for treatment of chronic ventricular arrhythmias: a 2-year experience. Am Heart J. 1988; 115:92-6. https://pubmed.ncbi.nlm.nih.gov/3336989

27. Kus T, Dubuc M, Lambert C et al. Efficacy of propafenone in preventing ventricular tachycardia: inverse correlation with rate-related prolongation of conduction time. J Am Coll Cardiol. 1990; 16:1229-37. https://pubmed.ncbi.nlm.nih.gov/2229772

28. Connolly SJ, Kates RE, Lebsack CS et al. Clinical pharmacology of propafenone. Circulation. 1983; 68:589-96. https://pubmed.ncbi.nlm.nih.gov/6872170

29. Mason JW for the Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. N Engl J Med. 1993; 329:452-8. https://pubmed.ncbi.nlm.nih.gov/8332150

30. Antiarrhythmic Drug Evaluation Group (A.D.E.G.). A multicentre, randomized trial on the benefit/risk profile of amiodarone, flecainide and propafenone in patients with cardiac disease and complex ventricular arrhythmias. Eur Heart J. 1992; 13:1251-8. https://pubmed.ncbi.nlm.nih.gov/1396837

31. Touboul P, Moleur P, Mathieu MP et al. A comparative evaluation of the effects of propafenone and lidocaine on early ventricular arrhythmias after acute myocardial infarction. Eur Heart J. 1988; 9:1188-93. https://pubmed.ncbi.nlm.nih.gov/3234410

32. Siebels J, Cappato R, Rüppel R et al and the CASH Investigators. Preliminary results of the Cardiac Arrest Study Hamburg (CASH). Am J Cardiol. 1993; 72:109-13F.

33. Hii JTY, Duff HJ, Burgess ED. Clinical pharmacokinetics of propafenone. Clin Pharmacokinet. 1991; 21:1-10. https://pubmed.ncbi.nlm.nih.gov/1914339

34. Katoh T, Karagueuzian HS, Sugi K et al. Effects of propafenone on sinus nodal and ventricular automaticity: in vitro and in vivo correlation. Am Heart J. 1987; 113:941-52. https://pubmed.ncbi.nlm.nih.gov/3565244

35. Klein RC, Huang SK, Marcus FI et al. Enhanced antiarrhythmic efficacy of propafenone when used in combination with procainamide or quinidine. Am Heart J. 1987; 114:551-8. https://pubmed.ncbi.nlm.nih.gov/3630896

36. Lee JT, Kroemer HK, Silberstein DJ et al. The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med. 1990; 322:1764-8. https://pubmed.ncbi.nlm.nih.gov/1971708

37. Zoble RG, Kirsten EB, Brewington J and the Propafenone Research Group. Pharmacokinetic and pharmacodynamic evaluation of propafenone in patients with ventricular arrhythmia. Clin Pharmacol Ther. 1989; 45:535-41. https://pubmed.ncbi.nlm.nih.gov/2721109

38. Dukes ID, Vaughan Williams EM. The multiple modes of action of propafenone. Eur Heart J. 1984; 5:115-25. https://pubmed.ncbi.nlm.nih.gov/6144546

39. Barbey JT. Clinical pharmacology and β-blocking efficacy of propafenone. J Cardiovasc Pharmacol. 1991; 17(Suppl 6):S41-3. https://pubmed.ncbi.nlm.nih.gov/1723117

40. Siddoway LA, Thompson KA, McAllister CB et al. Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation. 1987; 75:785-91. https://pubmed.ncbi.nlm.nih.gov/3829342

41. Haefeli EW, Vozeh S, Ha HR et al. Comparison of the pharmacodynamic effects of intravenous and oral propafenone. Clin Pharmacol Ther. 1990; 48:245-54. https://pubmed.ncbi.nlm.nih.gov/2401123

42. Lombardi F, Torzillo D, Sandrone G et al. Beta-blocking effect of propafenone based on spectral analysis of heart rate variability. Am J Cardiol. 1992; 70:1028-34. https://pubmed.ncbi.nlm.nih.gov/1357951

43. Burgess E, Duff H, Wilkes P. Propafenone disposition in renal insufficiency and renal failure. J Clin Pharmacol. 1989; 29:112-3. https://pubmed.ncbi.nlm.nih.gov/2715367

44. Singlas E, Fillastre JP. Pharmacokinetics of newer drugs in patients with renal impairment (Part II). Clin Pharmacokinet. 1991; 20:389-410. https://pubmed.ncbi.nlm.nih.gov/1879096

45. Philipsborn G, Gries J, Hofmann HP et al. Pharmacological studies on propafenone and its main metabolite 5-hydroxypropafenone. Arzneimittelforschung. 1984; 34:1489-97. https://pubmed.ncbi.nlm.nih.gov/6543124

46. McLeod AA, Stiles GL, Shand DG. Demonstration of beta adrenoceptor blockade by propafenone hydrochloride: clinical pharmacologic, radioligand binding and adenylate cyclase activation studies. J Pharmacol Exp Ther. 1984; 228:461-6. https://pubmed.ncbi.nlm.nih.gov/6141285

47. Ravid S, Podrid PJ, Novrit B. Safety of long-term propafenone therapy for cardiac arrhythmia—experience with 774 patients. J Electrophysiol. 1987; 1:580-90.

48. Rankin AC. Adverse effects of antiarrhythmic drugs. Adv Drug React Toxicol Rev. 1992; 11:173-91.

49. Veale D, McComb JM, Gibson GJ. Propafenone. Lancet. 1990; 335:979. https://pubmed.ncbi.nlm.nih.gov/1970054

50. Mondardini A, Pasquino P, Bernardi P et al. Propafenone-induced liver injury: report of a case and review of the literature. Gastroenterology. 1993; 104:1524-6. https://pubmed.ncbi.nlm.nih.gov/8482464

51. Jack RA. A case of mania secondary to propafenone. J Clin Psychiatry. 1985; 46:104-5. https://pubmed.ncbi.nlm.nih.gov/2579063

52. Lecky BRF, Weir D, Chong E. Exacerbation of myasthenia by propafenone. J Neurol Neurosurg Psychiatry. 1991; 54:377. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC488508/ https://pubmed.ncbi.nlm.nih.gov/2056335

53. Chua TP, Farrell T, Lipkin DP. Myoclonus associated with propafenone. BMJ. 1994; 308:113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2539204/ https://pubmed.ncbi.nlm.nih.gov/8298383

54. Anon. Propaphenone: fatal dysrhythmias. WHO Drug Info. 1991; 5:9.

55. Latini R, Marchi S, Riva E et al. Distribution of propafenone and its active metabolite, 5-hydroxypropafenone, in human tissues. Am Heart J. 1987; 113:843-4. https://pubmed.ncbi.nlm.nih.gov/3825881

56. Lee P-K, Kerr CR, Vorderbrugge S et al. Symptomatic sinus node dysfunction associated with the use of propafenone. Am J Cardiol. 1988; 62:480-1. https://pubmed.ncbi.nlm.nih.gov/3414526

57. Lange H, Lampert S, St John Sutton M et al. Changes in cardiac output determined by continuous-wave doppler echocardiography during propafenone or mexiletine drug testing. Am J Cardiol. 1990; 65:458-62. https://pubmed.ncbi.nlm.nih.gov/2305684

58. Podrid PJ, Lampert S, Graboys TB et al. Aggravation of arrhythmia by antiarrhythmic drugs—incidence and predictors. Am J Cardiol. 1987; 59:38-44E. https://pubmed.ncbi.nlm.nih.gov/2949580

59. Anon. Propafenone: an antiarrhythmic come in from the cold. Lancet. 1989; 2:1490-1. https://pubmed.ncbi.nlm.nih.gov/2574772

60. Puech P, Gagnol JP. Class IC drugs: propafenone and flecainide. Cardiovasc Drugs Ther. 1990; 4:549-54. https://pubmed.ncbi.nlm.nih.gov/2125832

61. Rehnqvist, Ericsson CG, Eriksson S et al. Comparative investigation of the antiarrhythmic effect of propafenone (Rytmonorm) and lidocaine in patients with ventricular arrhythmias during acute myocardial infarction. Acta Med Scand. 1984; 216:525-30. https://pubmed.ncbi.nlm.nih.gov/6395642

62. Vaughn Williams EM. Significance of classifying antiarrhythmic actions since the cardiac arrhythmia suppression trial. J Clin Pharmacol. 1991; 31:123-35. https://pubmed.ncbi.nlm.nih.gov/1901320

63. Spinler SA, Elder CA, Kindwall KE. Propafenone-induced liver injury. Ann Pharmacother. 1992; 26:926-8. https://pubmed.ncbi.nlm.nih.gov/1354511

64. Libardoni M, Piovan D, Busato E et al. Transfer of propafenone and 5-OH-propafenone to foetal plasma and maternal milk. Br J Clin Pharmacol. 1991; 32:527-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1368620/ https://pubmed.ncbi.nlm.nih.gov/1958453

65. Knoll Laboratories. Product information form for American hospital formulary service: Rythmol (propafenone hydrochloride) . Mount Olive, NJ; 1989 Dec 1.

66. The United States pharmacopeia, 23rd rev, and The national formulary, 18th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1995:1313.

67. Faber TS, Camm AJ. The differentiation of propafenone from other class Ic agents, focusing on the effect on ventricular response rate attributable to its beta-blocking action. Eur J Clin Pharmacol. 1996; 51:199-208. https://pubmed.ncbi.nlm.nih.gov/9010685

68. Capucci A, Boriani G. Propafenone in the treatment of cardiac arrhythmias: a risk-benefit appraisal. Drug Saf. 1995; 12:55-72. https://pubmed.ncbi.nlm.nih.gov/7741984

69. Lalka D, Griffith RK, Cronenberger CL. The hepatic first-pass metabolism of problematic drugs. J Clin Pharmacol. 1993; 33:657-69. https://pubmed.ncbi.nlm.nih.gov/8366191

70. Haefeli WE, Vozeh S, Ha HR et al. Concentration-effect relations of 5-hydroxypropafenone in normal subjects. Am J Cardiol. 1991; 67:1022-6. https://pubmed.ncbi.nlm.nih.gov/2018005

71. Vozeh S, Schmidlin O, Taeschner W. Pharmacokinetic drug data. Clin Pharmacokinet. 1988; :254-82. https://pubmed.ncbi.nlm.nih.gov/3191648

72. Brunozzi LT, Meniconi L, Chiocchi P et al. Propafenone in the treatment of chronic ventricular arrhythmias in a pregnant patient. Br J Clin Pharmacol. 1988; 26:489-90. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386576/ https://pubmed.ncbi.nlm.nih.gov/3191001

73. Connolly S, Lebsack C, Winkle RA et al. Propafenone disposition kinetics in cardiac arrhythmia. Clin Pharmacol Ther. 1984; 36:163-8. https://pubmed.ncbi.nlm.nih.gov/6744775

74. Podrid PJ, Levine PA, Klein MP. Effect of age on antiarrhythmic drug efficacy and toxicity. Am J Cardiol. 1989; 63:735-9. https://pubmed.ncbi.nlm.nih.gov/2646900

75. Podrid PJ, Anderson JL, for the Propafenone Multicenter Study Group. Safety and tolerability of long-term propafenone therapy for supraventricular tachyarrhythmias. Am J Cardiol. 1996; 78:430-4. https://pubmed.ncbi.nlm.nih.gov/8752188

76. Podczeck A, Frohner K, Hief C et al. Acute and long-term efficacy of propafenone in patients with sustained ventricular tachyarrhythmias: assessment with programmed ventricular stimulation. Eur Heart J. 1991; 12:796-9. https://pubmed.ncbi.nlm.nih.gov/1889445

77. Tisdale JE, Kluger J, Fisher JR et al. Efficacy of class 1C antiarrhythmic agents in patients with inducible ventricular tachycardia refractory to therapy with class 1A antiarrhythmic drugs. J Clin Pharmacol. 1993; 33:623-30. https://pubmed.ncbi.nlm.nih.gov/8366187

78. Podrid PJ, Lown B. Propafenone: a new agent for ventricular arrhythmia. J Am Coll Cardiol. 1984; 4:117-25. https://pubmed.ncbi.nlm.nih.gov/6376591

79. Podrid PJ, Cytryn R, Lown B. Propafenone: noninvasive evaluation of efficacy. Am J Cardiol. 1984; 54:53-9D.

80. Brodsky MA, Allen BJ, Abate D et al. Propafenone therapy for ventricular tachycardia in the setting of congestive heart failure. Am Heart J. 1985; 110:794-9. https://pubmed.ncbi.nlm.nih.gov/4050651

81. Chilson DA, Heger JJ, Zipes DP et al. Electrophysiologic effects and clinical efficacy of oral propafenone therapy in patients with ventricular tachycardia. J Am Coll Cardiol. 1985; 5:1407-13. https://pubmed.ncbi.nlm.nih.gov/3889099

82. Haffajee CI, Degon C, Huang SKS et al. Is programmed ventricular stimulation predictive of long term outcome in patients with malignant ventricular tachycardia taking propafenone? Circulation. 1989; 80 (Suppl II):II-652. Abstract No. 2589.

83. Yeung-Lai-Wah JA, Murdock CJ, Boone J et al. Propafenone-mexiletine combination for the treatment of sustained ventricular tachycardia. J Am Coll Cardiol. 1992; 20:547-51. https://pubmed.ncbi.nlm.nih.gov/1512331

84. Reimold SC, Cantillon CO, Friedman PL et al. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Am J Cardiol. 1993; 71:558-63. https://pubmed.ncbi.nlm.nih.gov/8438741

85. Salerno DM, Granrud G, Sharkey P et al. A controlled trial of propafenone for treatment of frequent and repetitive ventricular premature complexes. Am J Cardiol. 1984; 53:77-83. https://pubmed.ncbi.nlm.nih.gov/6362387

86. Schamroth L, Myburgh DP, Schamroth CL et al. Oral propafenone in the suppression of chronic stable ventricular arrhythmias. Chest. 1985; 87:448-51. https://pubmed.ncbi.nlm.nih.gov/3884286

87. de Soyza N, Terry L, Murphy ML et al. Effect of propafenone in patients with stable ventricular arrhythmias. Am Heart J. 1984; 108:285-9. https://pubmed.ncbi.nlm.nih.gov/6380253

88. Channer KS. The drug treatment of atrial fibrillation. Br J Clin Pharmacol. 1991; 32:267-73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1368517/ https://pubmed.ncbi.nlm.nih.gov/1685662

89. Ravi Kishore AG, Camm AJ. Guidelines for the use of propafenone in treating supraventricular arrhythmias. Drugs. 1995; 50:250-62. https://pubmed.ncbi.nlm.nih.gov/8521758

90. Grant AO. Propafenone: an effective agent for the management of supraventricular arrhythmias. J Cardiovasc Electrophysiol. 1996; 7:353-64. https://pubmed.ncbi.nlm.nih.gov/8777484

91. Cobbe SM. Drug therapy of supraventricular tachyarrhythmias—based on efficacy or futility? Eur Heart J. 1994; 15(Suppl A):22-6.

92. UK Propafenone PSVT Study Group. A randomized, placebo-controlled trial of propafenone in the prophylaxis of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. Circulation. 1995; 92:2550-7. https://pubmed.ncbi.nlm.nih.gov/7586356

93. Pritchett ELC, McCarthy EA, Wilkinson WE. Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias: a randomized, placebo-controlled, crossover trial in patients tolerating oral therapy. Ann Intern Med. 1991; 114:539-44. https://pubmed.ncbi.nlm.nih.gov/2001087

94. Allen BJ, Brodsky MA, Doria R et al. Oral propafenone therapy for patients with paroxysmal supraventricular tachyarrhythmia. Chest. 1988; 94:853-4. https://pubmed.ncbi.nlm.nih.gov/3168580

95. Shen EN, Keung E, Huycke E et al. Intravenous propafenone for termination of reentrant supraventricular tachycardia: a placebo-controlled, randomized, double-blind, crossover study. Ann Intern Med. 1986; 105:655-61. https://pubmed.ncbi.nlm.nih.gov/3767146

96. Dubuc M, Kus T, Campa MA et al. Electrophysiologic effects of intravenous propafenone in Wolff-Parkinson-White syndrome. Am Heart J. 1989; 117:370-6. https://pubmed.ncbi.nlm.nih.gov/2644795

97. Ludmer PL, McGowan NE, Antman EM et al. Efficacy of propafenone in Wolff-Parkinson-White syndrome: electrophysiologic findings and long-term follow-up. J Am Coll Cardiol. 1987; 9:1357-63. https://pubmed.ncbi.nlm.nih.gov/3294970

98. Boahene KA, Klein GJ, Yee R et al. Termination of acute atrial fibrillation in the Wolff-Parkinson-White syndrome by procainamide and propafenone: importance of atrial fibrillatory cycle length. J Am Coll Cardiol. 1990; 16:1408-14. https://pubmed.ncbi.nlm.nih.gov/2229793

99. Antman EM, Beamer AD, Cantillon C et al. Long-term oral propafenone therapy for suppression of refractory symptomatic atrial fibrillation and atrial flutter. J Am Coll Cardiol. 1988; 12:1005-11. https://pubmed.ncbi.nlm.nih.gov/3417972

100. Hammill SC, McLaran CJ, Wood DL et al. Double-blind study of intravenous propafenone for paroxysmal supraventricular reentrant tachycardia. J Am Coll Cardiol. 1987; 9:1364-8. https://pubmed.ncbi.nlm.nih.gov/3584724

101. Capucci A, Boriani G, Botto GL et al. Conversion of recent-onset atrial fibrillation by a single oral loading dose of propafenone or flecainide. Am J Cardiol. 1994; 74: 503-5. https://pubmed.ncbi.nlm.nih.gov/8059737

102. Lip GYH, Watson RDS, Singh SP. Drugs for atrial fibrillation. BMJ. 1995; 311:1631-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551512/ https://pubmed.ncbi.nlm.nih.gov/8555811

103. Suttorp MJ, Kingma JH, Jessurun ER et al. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. J Am Coll Cardiol. 1990; 16:1722-7. https://pubmed.ncbi.nlm.nih.gov/2123909

104. Bianconi L, Boccadamo R, Pappalardo A et al. Effectiveness of intravenous propafenone for conversion of atrial fibrillation and flutter of recent onset. Am J Cardiol. 1989; 64:335-8. https://pubmed.ncbi.nlm.nih.gov/2667304

105. Connolly SJ, Hoffert DL. Usefulness of propafenone for recurrent paroxysmal atrial fibrillation. Am J Cardiol. 1989; 63:817-9. https://pubmed.ncbi.nlm.nih.gov/2648787

106. Vita JA, Friedman PL, Cantillon C et al. Efficacy of intravenous propafenone for the acute management of atrial fibrillation. Am J Cardiol. 1989; 63:1275-8. https://pubmed.ncbi.nlm.nih.gov/2711997

107. Porterfield JG, Porterfield LM. Therapeutic efficacy and safety of oral propafenone for atrial fibrillation. Am J Cardiol. 1989; 63:114-6. https://pubmed.ncbi.nlm.nih.gov/2909141

108. Hammill SC, Wood DL, Gersh BJ et al. Propafenone for paroxysmal atrial fibrillation. Am J Cardiol. 1988; 61:473-4. https://pubmed.ncbi.nlm.nih.gov/3341233

109. Boriani G, Biffi M, Capucci A et al. Oral propafenone to convert recent-onset atrial fibrillation in patients with and without underlying heart disease: a randomized, controlled trial. Ann Intern Med. 1997; 126:621-5. https://pubmed.ncbi.nlm.nih.gov/9103129

110. Stroobandt R, Stiels B, Hoebrechts R et al. Propafenone for conversion and prophylaxis of atrial fibrillation. Am J Cardiol. 1997; 79:418-23. https://pubmed.ncbi.nlm.nih.gov/9052343

111. Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med. 1997; 336:1429-34. https://pubmed.ncbi.nlm.nih.gov/9145681

112. Weiner B. Second generation antidysrhythmic agents. Crit Care Nurs Clin North Am. 1989; 1:417-22. https://pubmed.ncbi.nlm.nih.gov/2684236

113. Hussar DA. New drugs of 1990. Am Pharm. 1991; NS31:54-. https://pubmed.ncbi.nlm.nih.gov/2028913

114. Hopkins SJ. Propafenone. Drugs Today. 1989; 25:573-6.

115. Köppel C, Oberdisse U, Heinemeyer G. Clinical course and outcome in class IC antiarrhythmic overdose. Clin Toxicol. 1990; 28:433-44.

116. Roden DM. Risks and benefits of antiarrhythmic therapy. N Engl J Med. 1994; 331:785-91. https://pubmed.ncbi.nlm.nih.gov/8065408

117. Morganroth J, Bigger JT Jr. Pharmacologic management of ventricular arrhythmias after the cardiac arrhythmia suppression trial. Am J Cardiol. 1990; 65:1497-503. https://pubmed.ncbi.nlm.nih.gov/2091621

118. Tisdale JE, Webb CR. Are antiarrhythmic drugs obsolete? Clin Pharm. 1992; 11:714-26.

119. Murdock CJ, Kyles AE, Yeung-Lai-Wah JA et al. Atrial flutter in patients treated for atrial fibrillation with propafenone. Am J Cardiol. 1990; 66:755-7. https://pubmed.ncbi.nlm.nih.gov/2399896

120. Podrid PJ. Aggravation of ventricular arrhythmia: a drug-induced complication. Drugs. 1985; 29(Suppl 4):33-44. https://pubmed.ncbi.nlm.nih.gov/3924550

121. Anon. Drugs that cause psychiatric symptoms. Med Lett Drugs Ther. 1993; 35:65-70. https://pubmed.ncbi.nlm.nih.gov/8321161

122. Feld GK, Nademanee K, Singh BN et al. Hemodynamic and electrophysiologic effects of combined infusion of lidocaine and propafenone in humans. J Clin Pharmacol. 1987; 27:52-9. https://pubmed.ncbi.nlm.nih.gov/3680555

123. Funck-Brentano C, Kroemer HK, Pavlou H et al. Genetically-determined interaction between propafenone and low dose quinidine: role of active metabolites in modulating net drug effect. Br J Clin Pharmacol. 1989; 27:435-44. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1379722/ https://pubmed.ncbi.nlm.nih.gov/2719900

124. Bigot MC, Debruyne D, Bonnefoy L et al. Serum digoxin levels related to plasma propafenone levels during concomitant treatment. J Clin Pharmacol. 1991; 31:521-6. https://pubmed.ncbi.nlm.nih.gov/1880217

125. Calvo MV, Martin-Suarez A, Luengo CM et al. Interaction between digoxin and propafenone. Ther Drug Monit. 1989; 11:10-5. https://pubmed.ncbi.nlm.nih.gov/2911842

126. Latini R, Barbieri E, Castello C et al. Propafenone and 5-hydroxypropafenone concentrations in the right atrium of patients undergoing heart surgery. Am Heart J. 1989; 117:497-8. https://pubmed.ncbi.nlm.nih.gov/2916423

127. Lee BL, Dohrmann ML. Theophylline toxicity after propafenone treatment: evidence for drug interaction. Clin Pharmacol Ther. 1992; 51:353-5. https://pubmed.ncbi.nlm.nih.gov/1544292

128. Axelson JE, Chan GL Y, Kirsten EB et al. Food increases the bioavailability of propafenone. Br J Clin Pharmacol. 1987; 23:735-41. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1386169/ https://pubmed.ncbi.nlm.nih.gov/3606933

129. Chimienti M, Cullen MT Jr, Casadei G, for the Flecainide and Propafenone Italian Study (FAPIS) Investigators. Am J Cardiol. 1996; 77:60-5A.

130. Capucci A, Boriani G, Marchesini B et al. Minimal effective concentration values of propafenone and 5-hydroxy-propafenone in acute and chronic therapy. Cardiovasc Drugs Ther. 1990; 4:281-7. https://pubmed.ncbi.nlm.nih.gov/2285622

131. Botsch S, Gautier JP, Beaune P et al. Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Mol Pharmacol. 1993; 43:120-6. https://pubmed.ncbi.nlm.nih.gov/8423765

132. Cobbe SM. A randomized, placebo-controlled trial of propafenone in the prophylaxis of paroxysmal supraventricular tachyarrhythmias. J Am Coll Cardiol. 1994; Feb:251A.

133. Reimold SC, Antman EM. Meta-analysis of the efficacy of propafenone for treating supraventricular arrhythmias. Circulation Suppl. 1996; 94:I-665.

134. Delgado C, Tamargo J, Tejerina T. Electrophysiological effects of propafenone in untreated and propafenone-pretreated guinea-pig atrial and ventricular muscle fibres. Br J Pharmacol. 1985; 86:765-75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916619/ https://pubmed.ncbi.nlm.nih.gov/4075015

135. Honjo H, Watanabe T, Kamiya K et al. Effects of propafenone on electrical and mechanical activities of single ventricluar myocytes isolated from guinea-pig hearts. Br J Pharmacol. 1989; 97:731-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1854590/ https://pubmed.ncbi.nlm.nih.gov/2758239

136. Hege HG, Hollmann M, Kaumeier S et al. The metabolic fate of² H-labelled propafenone in man. Eur J Drug Metab Pharmacokinet. 1984; 9:41-55. https://pubmed.ncbi.nlm.nih.gov/6714269

137. Ledda F, Mantelli L, Manzini S et al. Electrophysiological and antiarrhythmic properties of propafenon in isolated cardiac preparations. J Cardiovasc Pharmacol. 1981; 3:1162-73. https://pubmed.ncbi.nlm.nih.gov/6173515

138. Hollmann M, Brode E, Hotz D et al. Investigations on the pharmacokinetics of propafenone in man. Arzneimittelforschung. 1983; 33:763-70. https://pubmed.ncbi.nlm.nih.gov/6683556

139. Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984; 24:129-47. https://pubmed.ncbi.nlm.nih.gov/6144698

140. Maisel WH, Kuntz KM, Reimold SC et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med. 1997; 127:281-4. https://pubmed.ncbi.nlm.nih.gov/9265427

141. Campbell TJ. Kinetics of onset of rate-dependent effects of class I antiarrhythmic drugs are important in determining their effects on refractoriness in guinea-pig ventricle, and provide a theoretical basis for their subclassification. Cardiovasc Res. 1983; 17:344-52. https://pubmed.ncbi.nlm.nih.gov/6883410

142. Connolly SJ, Kates RE, Lebsack CS et al. Clinical efficacy and electrophysiology of oral propafenone for ventricular tachycardia. Am J Cardiol. 1983; 52:1208-13. https://pubmed.ncbi.nlm.nih.gov/6359849

143. Prystowsky EN, Heger JJ, Chilson DA et al. Antiarrhythmic and electrophysiologic effects of oral propafenone. Am J Cardiol. 1984; 54:26-8D.

144. Stoschitzky K, Klein W, Stark G et al. Different stereoselective effects of (R)- and (S)-propafenone: clinical pharmacologic, electrophysiologic, and radioligand binding studies. Clin Pharmacol Ther. 1990; 47:740-6. https://pubmed.ncbi.nlm.nih.gov/2162749

145. Seipel L, Hoffmeister HM. Hemodynamic effects of antiarrhythmic drugs: negative inotropy versus influence on peripheral circulation. Am J Cardiol. 1989; 64:37-40J. https://pubmed.ncbi.nlm.nih.gov/2741812

146. Musto B, D’Onofrio A, Cavallaro C et al. Electrophysiological effects and clinical efficacy of propafenone in children with recurrent paroxysmal supraventricular tachycardia. Circulation. 1988; 78:863-9. https://pubmed.ncbi.nlm.nih.gov/3168194

147. Baker BJ, de Soyza N, Boyd CM et al. Effects of propafenone on left ventricular function. Circulation. 1982; 67:II-267.

148. Ruskin JN. The Cardiac Arrhythmia Suppression Trial (CAST). N Engl J Med. 1989; 321:386-8. https://pubmed.ncbi.nlm.nih.gov/2501683

149. The Cardiac Arrhythmia Suppression Trial (CAST) investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989; 321:406-12. https://pubmed.ncbi.nlm.nih.gov/2473403

150. Pratt CM, Brater DC, Harrell FE Jr et al. Clinical and regulatory implications of the Cardiac Arrhythmia Suppression Trial. Am J Cardiol. 1990; 65:103-5. https://pubmed.ncbi.nlm.nih.gov/1688479

151. Garratt C, Ward DE, Camm AJ. Lessons from the cardiac arrhythmia suppression trial. BMJ. 1989; 299:805-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1837677/ https://pubmed.ncbi.nlm.nih.gov/2510839

152. Anon. Restrictions on use of flecainide, encainide. FDA Drug Bull. 1989; 16.

153. Anon. Flecainide and CAST. Lancet. 1989; 2:481-2. https://pubmed.ncbi.nlm.nih.gov/2570188

154. Ward D, Garratt C, Camm AJ. Cardiac arrhythmia suppression trial and flecainide. Lancet. 1989; 1:1267-8. https://pubmed.ncbi.nlm.nih.gov/2566810

155. Echt DS, Liebson PR, Mitchell LB et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991; 324:781-8. https://pubmed.ncbi.nlm.nih.gov/1900101

156. Epstein AE, Hallstrom AP, Rogers WJ et al. mortality following ventricular arrhythmia suppression by encainide, flecainide, and moricizine after myocardial infarction: the original design concept of the Cardiac Arrhythmia Suppression Trial (CAST). JAMA. 1993; 270:2451-5. https://pubmed.ncbi.nlm.nih.gov/8230622

157. Vlay SC. Lessons from the past and reflections on the Cardiac Arrhythmia Suppression trial. Am J Cardiol. 1990; 65:112-3. https://pubmed.ncbi.nlm.nih.gov/1688480

158. Van Gelder IC, Brugemann J, Crijns HJGM. Pharmacological management of arrhythmias in the elderly. Drugs Aging. 1997; 11:96-110. https://pubmed.ncbi.nlm.nih.gov/9259173

159. Anon. CAST deaths revealed. Lancet. 1991; 337:969.

160. Botto GL, Bonini W, Broffoni T et al. Conversion of recent onset atrial fibrillation with single loading oral dose of propafenone: is in-hospital admission absolutely necessary? Pacing Clin Electrophysiol. 1996; 19(11 Part 2):1939-43.

161. Robson RH. Indications for flecainide. Lancet. 1989; 2:113.

162. Luedtke SA, Kuhn RJ, McCaffrey FM. Pharmacologic management of supraventricular tachycardias in children. Part 1: Wolff-Parkinson-White and atrioventricular nodal reentry. Ann Pharmacother. 1997; 31:1227-43. https://pubmed.ncbi.nlm.nih.gov/9337449

163. Coyle JD, Schaal SF. An interim perspective on the removal of encainide and flecainide from the Cardiac Arrhythmia Suppression Trial. DICP. 1989; 23:478-9. https://pubmed.ncbi.nlm.nih.gov/2500783

164. Food and Drug Administration. FDA Cardio-renal Advisory Committee will review CAST study. FDC Rep. 1989(Aug 14):3-4.

165. Luedtke SA, Kuhn RJ, McCaffrey FM. Pharmacologic management of supraventricular tachycardias in children. Part 2: Atrial flutter, atrial fibrillation, and junctional and atrial ectopic tachycardia. Ann Pharmacother. 1997; 31:1347-59. https://pubmed.ncbi.nlm.nih.gov/9391691

166. Nightingale SL. Flecainide and encainide not to be used in non-life-threatening arrhythmias. JAMA. 1989; 261:3368. https://pubmed.ncbi.nlm.nih.gov/2498536

167. Eagleton G. Dear doctor letter regarding appropriate uses of Tambocor. St. Paul, MN: 3M Riker; 1989 May.

168. Caron J, Libersa C. Adverse effects of class I antiarrhythmic drugs. Drug Saf. 1997; 17:8-36. https://pubmed.ncbi.nlm.nih.gov/9258628

169. Flaker GC, Blackshear JL, McBride R et al. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. J Am Coll Cardiol. 1992; 20:527-32. https://pubmed.ncbi.nlm.nih.gov/1512329

170. Coplen SE, Antman EM, Berlin JA et al. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion: a meta-analysis of randomized control trials. Circulation. 1990; 82:1106-16. https://pubmed.ncbi.nlm.nih.gov/2144796

171. Baker BJ, Brodsky MA, Dinh H et al. Hemodynamic effect of propafenone and the experience in patients with congestive heart failure. J Electrophysiol. 1987; 1:527-35.

172. Krenzer M. (Food and Drug Administration, Drug Information Branch): Personal communication; 1997 Sep 22.

173. Hill MR, Gotz VP, Harman E et al. Evaluation of the asthmogenicity of propafenone, a new antiarrhythmic drug: comparison of spirometry with methacholine challenge. Chest. 1986; 90:698-702. https://pubmed.ncbi.nlm.nih.gov/3533454

174. Vozeh S, Haefeli W, Ha HR et al. Nonlinear kinetics of propafenone metabolites in healthy man. Eur J Clin Pharmacol. 1990; 38:509-13. https://pubmed.ncbi.nlm.nih.gov/2379537

175. Kroemer HK, Funck-Brentano C, Silberstein DJ et al. Stereoselective disposition and pharmacologic activity of propafenone enantiomers. Circulation. 1989; 79:1068-76. https://pubmed.ncbi.nlm.nih.gov/2713973

176. Kroemer HK, Fromm MF, Eichelbaum M. Stereoselectivity in drug metabolism and action: effects of enzyme inhibition and induction. Ther Drug Monit. 1996; 18:388-92. https://pubmed.ncbi.nlm.nih.gov/8857556

177. Kroemer HK, Fromm MF, Bühl K et al. An enantiomer-enantiomer interaction of (S)- and (R)-propafenone modifies the effect of racemic drug therapy. Circulation. 1994; 89:2396-400. https://pubmed.ncbi.nlm.nih.gov/7910120

178. Lee JT, Yee YG, Dorian P et al. Influence of hepatic dysfunction on the pharmacokinetics of propafenone. J Clin Pharmacol. 1987; 27:384-9. https://pubmed.ncbi.nlm.nih.gov/3693582

179. Fromm MF, Botsch S, Heinkele G et al. Influence of renal function on the steady-state pharmacokinetics of the antiarrhythmic propafenone and its phase I and phase II metabolites. Eur J Clin Pharmacol. 1995; 48:279-83. https://pubmed.ncbi.nlm.nih.gov/7589055

180. Seipel L, Breithardt G. Propafenone—a new antiarrhythmic drug. Eur Heart J. 1980; 1:309-13. https://pubmed.ncbi.nlm.nih.gov/7023945

181. Giani P, Landolina M, Giudici V et al. Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration. Eur J Clin Pharmacol. 1988; 34:187-94. https://pubmed.ncbi.nlm.nih.gov/3383990

182. Frabetti L, Marchesini B, Capucci A et al. Antiarrhythmic efficacy of propafenone: evaluation of effective plasma levels following single and multiple doses. Eur J Clin Pharmacol. 1986; 30:665-71. https://pubmed.ncbi.nlm.nih.gov/2429844

183. Golzari H, Cebul RD, Bahler RC. Atrial fibrillation: restoration and maintenance of sinus rhythm and indications for anticoagulation therapy. Ann Intern Med. 1996; 125:311-23. https://pubmed.ncbi.nlm.nih.gov/8678396

184. Kates RE, Yee YG, Winkle RA. Metabolite cumulation during chronic propafenone dosing in arrhythmia. Clin Pharmacol Ther. 1985; 37:610-4. https://pubmed.ncbi.nlm.nih.gov/4006362

185. Reviewers’ comments (personal observations) on encainide 24:04.

186. Steurer G, Weber H, Schmidinger H et al. Plasma propafenone concentration in the evaluation of anti-arrhythmic efficacy. Eur Heart J. 1991; 12:526-32. https://pubmed.ncbi.nlm.nih.gov/2065687

187. O’Rourke DJ, Palac RT, Holzberger PT et al. Propafenone-induced drug fever in the absence of agranulocytosis. Clin Cardiol. 1997; 20:662-4. https://pubmed.ncbi.nlm.nih.gov/9220185

188. Chan GLY, Axelson JE, Price JDE et al. In vitro protein binding of propafenone in normal and uraemic human sera. Eur J Clin Pharmacol. 1989; 36:495-9. https://pubmed.ncbi.nlm.nih.gov/2753068

189. Malfatto G, Zaza A, Forster M et al. Electrophysiologic, inotropic and antiarrhythmic effects of propafenone, 5-hydroxypropafenone and N-depropylpropafenone. J Pharmacol Exp Ther. 1988; 246:419-26. https://pubmed.ncbi.nlm.nih.gov/3404440

190. Kroemer HK, Mikus G, Kronbach T et al. In vitro characterization of the human cytochrome P-450 involved in polymorphic oxidation of propafenone. Clin Pharmacol Ther. 1989; 45:28-33. https://pubmed.ncbi.nlm.nih.gov/2910635

191. Brode E, Müller-Peltzer H, Hollmann M. Comparative pharmacokinetics and clinical pharmacology of propafenone enantiomers after oral administration to man. Methods Find Exp Clin Pharmacol. 1988; 10:717-27. https://pubmed.ncbi.nlm.nih.gov/3221745

192. Kroemer HK, Fischer C, Meese CO et al. Enantiomer/enantiomer interaction of (S)- and (R)-propafenone for cytochrome P450IID6-catalyzed 5-hydroxylation: in vitro evaluation of the mechanism. Mol Pharmacol. 1991; 40:135-42. https://pubmed.ncbi.nlm.nih.gov/1857335

193. McHugh TP, Perina DG. Propafenone ingestion. Ann Emer Med. 1987; 16:437-40.

194. Knoll Pharmaceutical Company, Mount Olive, NJ: Personal communication.

195. Azpitarte J, Alvarez M, Baún O et al. Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Eur Heart J. 1997; 18:1649-54. https://pubmed.ncbi.nlm.nih.gov/9347277

196. Botto GL, Capucci A, Bonini W et al. Conversion of recent onset atrial fibrillation to sinus rhythm using a single oral loading dose of propafenone: comparison of two regimens. Intl J Cardiol. 1997; 58:55-61.

197. Connolly SJ, Mulji AS, Hoffert DL et al. Randomized placebo-controlled trial of propafenone for treatment of atrial tachyarrhythmias after cardiac surgery. J Am Coll Cardiol. 1987; 10:1145-8. https://pubmed.ncbi.nlm.nih.gov/3499456

198. Merrick AF, Odom NJ, Keenan DJM et al. Comparison of propafenone to atenolol for the prophylaxis of postcardiotomy supraventricular tachyarrhythmias: a prospective trial. Eur J Cardiothorac Surg. 1995; 9:146-9. https://pubmed.ncbi.nlm.nih.gov/7786531

199. Weiner P, Ganam R, Ganem R et al. Clinical course of recent-onsent atrial fibrillation treated with oral propafenone. Chest. 1994; 105:1013-6. https://pubmed.ncbi.nlm.nih.gov/8162718

200. Aliot E, Denjoy I, and the Flecainide AF French Study Group. Comparison of the safety and efficacy of flecainide versus propafenone in hospital out-patients with symptomatic paroxysmal atrial fibrillation/flutter. Am J Cardiol. 1996; 77:66A-71. https://pubmed.ncbi.nlm.nih.gov/8607394

201. Crijns HJGM, Gosselink ATM, Lie KI et al. Propafenone versus disopyramide for maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation: a randomized, double-blind study. Cardiovasc Drugs Ther. 1996; 10:145-52. https://pubmed.ncbi.nlm.nih.gov/8842506

202. Lee SH, Chen SA, Chiang CE et al. Comparisons of oral propafenone and quinidine as an initial treatment option in patients with symptomatic paroxysmal atrial fibrillation: a double-blind, randomized trial. J Intern Med. 1996; 239:253-60. https://pubmed.ncbi.nlm.nih.gov/8772625

203. Bianconi L, Mennuni M, Lukic V et al. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. J Am Coll Cardiol. 1996; 28:700-6. https://pubmed.ncbi.nlm.nih.gov/8772759

204. Sager PT. Atrial fibrillation: antiarrhythmic therapy versus rate control with antithrombotic therapy. Am J Cardiol. 1997; 80:74G-81. https://pubmed.ncbi.nlm.nih.gov/9354414

205. Lee SH, Chen SA, Tai CT et al. Comparisons of oral propafenone and sotalol as an initial treatment in patients with symptomatic paroxysmal atrial fibrillation. Am J Cardiol. 1997; 79:905-8. https://pubmed.ncbi.nlm.nih.gov/9104904

206. Antman EM, Beamer AD, Cantillon C et al. Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs. J Am Coll Cardiol. 1990; 15:698-707. https://pubmed.ncbi.nlm.nih.gov/2303641

207. Fresco C, Proclemer A, Pavan A et al et al. Intravenous propafenone in paroxysmal atrial fibrillation: a randomized, placebo-controlled, double-blind, multicenter clinical trial. Clin Cardiol. 1996; 19:409-12. https://pubmed.ncbi.nlm.nih.gov/8723601

208. Boriani G, Capucci A, Lenzi T et al. Propafenone for conversion of recent-onset atrial fibrillation: a controlled comparison between oral loading dose and intravenous administration. Chest. 1995; 108:355-8. https://pubmed.ncbi.nlm.nih.gov/7634866

209. Bellandi F, Dabizzi RP, Cantini F et al. Intravenous propafenone: efficacy and safety in the conversion to sinus rhythm of recent onset atrial fibrillation—a single-blind placebo-controlled study. Cardiovasc Drugs Ther. 1996; 10:153-7. https://pubmed.ncbi.nlm.nih.gov/8842507

210. Zehender M, Hohnloser S, Geibel A et al. Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients with symptoms. Br Heart J. 1992; 67:491-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1024894/ https://pubmed.ncbi.nlm.nih.gov/1622701

211. Jung F, DiMarco JP. Treatment strategies for atrial fibrillation. Am J Med. 1998; 104:272-86. https://pubmed.ncbi.nlm.nih.gov/9552091

212. Reimer A, Paul T, Kallfelz HC. Efficacy and safety of intravenous and oral propafenone in pediatric cardiac dysrhythmias. Am J Cardiol. 1991; 68:741-4. https://pubmed.ncbi.nlm.nih.gov/1892080

213. Janousek J, Paul T, Reimer A et al. Usefulness of propafenone for supraventricular arrhythmias in infants and children. Am J Cardiol. 1993; 72:294-300. https://pubmed.ncbi.nlm.nih.gov/8342507

214. Paul T, Janousek J. New antiarrhythmic drugs in pediatric use: propafenone. Pediatr Cardiol. 1994; 15:190-7. https://pubmed.ncbi.nlm.nih.gov/7991437

215. Olm M, Munne P, Jimenez MJ. Severe reactive airways disease induced by propafenone. Chest. 1989; 95:1366-7. https://pubmed.ncbi.nlm.nih.gov/2721285

216. Guccione P, Drago F, Di Donato RM et al. Oral propafenone therapy for children with arrhythmias: efficacy and adverse effects in midterm follow-up. Am Heart J. 1991; 122:1022-7. https://pubmed.ncbi.nlm.nih.gov/1927853

217. Paul T, Reimer A, Janousek J et al. Efficacy and safety of propafenone in congenital junctional ectopic tachycardia. J Am Coll Cardiol. 1992; 20:911-4. https://pubmed.ncbi.nlm.nih.gov/1527301

218. Beaufort-Krol GCM, Bink-Boelkens MTE. Oral propafenone as treatment for incessant supraventricular and ventricular tachycardia in children. Am J Cardiol. 1993; 72:1213-4. https://pubmed.ncbi.nlm.nih.gov/8237821

219. Vignati G, Mauri L, Figini A. The use of propafenone in the treatment of tachyarrhythmias in children. Eur Heart J. 1993; 14:546-50. https://pubmed.ncbi.nlm.nih.gov/8472721

220. Fish FA, Mehta AV, Johns JA. Characteristics and management of chaotic atrial tachycardia of infancy. Am J Cardiol. 1996; 78:1052-5. https://pubmed.ncbi.nlm.nih.gov/8916490

221. Miwa LJ, Jolson HM. Propafenone associated agranulocytosis. PACE. 1992; 15:387-90. https://pubmed.ncbi.nlm.nih.gov/1374882

222. Jones RJ, Brace SR, Vander Tuin EL. Probable propafenone-induced transient global amnesia. Ann Pharmacother. 1995; 29:586-90. https://pubmed.ncbi.nlm.nih.gov/7663030

223. Galasso PJ, Stanton MS, Vogel H. Propafenone-induced peripheral neuropathy. Mayo Clin Proc. 1995; 70:469-72. https://pubmed.ncbi.nlm.nih.gov/7731257

224. Sulke AN, Holt P, Sowton GE. Acceleration of conduction within an accessory pathway with propafenone. Int J Cardiol. 1990; 28:105-7. https://pubmed.ncbi.nlm.nih.gov/2365521

225. Schüppel R, Probst M. Acute cholestatic hepatitis and the sudden rise of the pacing threshold 5 weeks after VVI-pacemaker implantation. J Intern Med. 1994; 236:353-6. https://pubmed.ncbi.nlm.nih.gov/8077895

226. Mörike K, Magadum S, Mettang T et al. Propafenone in a usual dose produces severe side-effects: the impact of genetically determined metabolic status on drug therapy. J Intern Med. 1995; 238:469-72. https://pubmed.ncbi.nlm.nih.gov/7595187

227. Hii JTY, Wyse DG, Gillis AM et al. Propafenone-induced torsade de pointes: cross-reactivity with quinidine. PACE. 1991; 14:1568-70. https://pubmed.ncbi.nlm.nih.gov/1721143

228. Scanu P, Grollier G, Guilleman D et al. Malignant ventricular tachycardia during propafenone treatment in a child with junctional automatic tachycardia: effectiveness of intravenous molar sodium lactate. PACE. 1991; 14:783-6. https://pubmed.ncbi.nlm.nih.gov/1712954

229. Montefoschi N, Boccadamo R. Propafenone induced acute variation of chronic atrial pacing threshold: a case report. PACE. 1990; 13:480-3. https://pubmed.ncbi.nlm.nih.gov/1692131

230. Reimold SC. Avoiding drug problems: the safety of drugs for supraventricular tachycardia. Eur Heart J. 1997; 18(Suppl C):C40-4. https://pubmed.ncbi.nlm.nih.gov/9152674

231. Maisel WH, Kuntz KM, Reimold SC et al. Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med. 1997; 127:281-4. https://pubmed.ncbi.nlm.nih.gov/9265427

232. Falk RH. Proarrhythmia in patients treated for atrial fibrillation or flutter. Ann Intern Med. 1992; 117:141-50. https://pubmed.ncbi.nlm.nih.gov/1605429

233. Chimienti M, Cullen MT Jr, Casadei G et al. Safety of flecainide versus propafenone for the long-term management of symptomatic paroxysmal supraventricular tachyarrhythmias: report from the Flecainide and Propafenone Italian Study (FAPIS) Group. Eur Heart J. 1995; 16:1943-51. https://pubmed.ncbi.nlm.nih.gov/8682031

234. Moroe K, Annoura M, Matsuo K et al. Proarrhythmic effects of class Ic drugs. Clin Ther. 1993; 15:559-66. https://pubmed.ncbi.nlm.nih.gov/8364947

235. Morganroth J. Proarrhythmic effects of antiarrhythmic drugs: evolving concepts. Am Heart J. 1992; 123:1137-9. https://pubmed.ncbi.nlm.nih.gov/1553883

236. Santinelli V, Arnese M, Oppo I et al. Effects of flecainide and propafenone on systolic performance in subjects with normal cardiac function. Chest. 1993; 103:1068-73. https://pubmed.ncbi.nlm.nih.gov/8131440

237. Pratt CM, Moyé LA. The cardiac arrhythmia suppression trial: casting suppression in a different light. Circulation. 1995; 91:245-7. https://pubmed.ncbi.nlm.nih.gov/7805210

238. Kerns W II, English B, Ford M. Propafenone overdose. Ann Emerg Med. 1994; 24:98-103. https://pubmed.ncbi.nlm.nih.gov/8010557

239. Maxeiner H, Klug E. Lethal suicidal intoxication with propafenone, after a history of self-inflicted injuries. Forensic Sci Int. 1997; 89:27-32. https://pubmed.ncbi.nlm.nih.gov/9306661

240. Chouty F, Funck-Brentano C, Leenhardt A et al. Intravenous sodium lactate as a treatment of class I anti-arrhythmic agents overdose. Circulation. 1989; 80(Suppl II):II-430.

241. Mörike KE, Roden DM. Quinidine-enhanced β-blockade during treatment with propafenone in extensive metabolizer human subjects. Clin Pharmacol Ther. 1994; 55:28-34. https://pubmed.ncbi.nlm.nih.gov/7905369

242. Libersa C, Caron J, Broly F et al. Interaction of propafenone and mexiletine. J Am Coll Cardiol. 1993; 22:2061. https://pubmed.ncbi.nlm.nih.gov/8245368

243. Kerr CR, Yeung-Lai-Wah J. Interaction of propafenone and mexiletine. J Am Coll Cardiol. 1993; 22:2061-2. https://pubmed.ncbi.nlm.nih.gov/8245368

244. Ujhelyi MR, O’Rangers EA, Fan C et al. The pharmacokinetic and pharmacodynamic interaction between propafenone and lidocaine. Clin Pharmacol Ther. 1993; 53:38-48. https://pubmed.ncbi.nlm.nih.gov/8422740

245. Zalzstein E, Koren G, Bryson SM et al. Interaction between digoxin and propafenone in children. J Pediatr. 1990; 116:310-2. https://pubmed.ncbi.nlm.nih.gov/2299507

246. Kowey PR, Kirsten EB, Fu CHJ et al. Interaction between propranolol and propafenone in healthy volunteers. J Clin Pharmacol. 1989; 29:512-7. https://pubmed.ncbi.nlm.nih.gov/2754020

247. Wagner F, Kalusche D, Trenk D et al. Drug interaction between propafenone and metoprolol. Br J Clin Pharmacol. 1987; 24:213-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1387752/ https://pubmed.ncbi.nlm.nih.gov/3620296

248. Kates RE, Yee YG, Kirsten EB. Interaction between warfarin and propafenone in healthy volunteer subjects. Clin Pharmacol Ther. 1987; 42:305-11. https://pubmed.ncbi.nlm.nih.gov/3621785

249. Pritchett ELC, Smith WM, Kirsten EB. Pharmacokinetic and pharmacodynamic interactions of propafenone and cimetidine. J Clin Pharmacol. 1988; 28:619-24. https://pubmed.ncbi.nlm.nih.gov/3063727

250. Spes CH, Angermann CE, Horn K et al. Ciclosporin-propafenone interaction. Klin Wochenschr. 1990; 68:872. https://pubmed.ncbi.nlm.nih.gov/2214612

251. Katz MR. Raised serum levels of desipramine with the antiarrhythmic propafenone. J Clin Psychiatry. 1991; 52:432-3. https://pubmed.ncbi.nlm.nih.gov/1938981

252. Spinler SA, Gammaitoni A, Charland SL et al. Propafenone-theophylline interaction. Pharmacotherapy. 1993; 13:68-71. https://pubmed.ncbi.nlm.nih.gov/8437970

253. Ahmad S. Metoprolol-induced delirium perpetuated by propafenone. Am Fam Physician. 1991; 44:1142-4. https://pubmed.ncbi.nlm.nih.gov/1927831

254. Zipes DP. A consideration of antiarrhythmic therapy. Circulation. 1985; 72:949-56. https://pubmed.ncbi.nlm.nih.gov/3930087

255. Coumel P, Chouty F, Slama R. Logic and empiricism in the selection of antiarrhythmic agents: the role of drug combinations. Drugs. 1985; 29(Suppl 4):68-76. https://pubmed.ncbi.nlm.nih.gov/4006782

256. Koytchev R, Alken RG, Mayer O et al. Influence of food on the bioavailability and some pharmacokinetic parameters of diprafenone–a novel antiarrhythmic agent. Eur J Clin Pharmacol. 1996; 50:315-9. https://pubmed.ncbi.nlm.nih.gov/8803526

257. Spence JD. Drug interactions with grapefruit: whose responsibility is it to warn the public? Clin Pharmacol Ther. 1997; 61:395-400. (IDIS 385684)

258. Shader RI, Greenblatt DJ. Fruit juices and pharmacology. J Clin Psychopharmacol. 1997; 17:245-6. https://pubmed.ncbi.nlm.nih.gov/9241001

259. Roller L. Drugs and grapefruit juice. Clin Pharmacol Ther. 1998; 63:87. https://pubmed.ncbi.nlm.nih.gov/9465845

260. Spence JD. Drugs and grapefruit juice. Clin Pharmacol Ther. 1998; 63:87-8. https://pubmed.ncbi.nlm.nih.gov/9465845

261. Weiner M. Informing the public. Clin Pharmacol Ther. 1997; 62:578-9. https://pubmed.ncbi.nlm.nih.gov/9390116

262. Spence JD. Informing the public. Clin Pharmacol Ther. 1997; 62:579. https://pubmed.ncbi.nlm.nih.gov/9390117

263. Boucher M, Chassaing C, Hamel JD et al. Cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in the conscious dog. Eur J Pharmacol. 1996; 315:171-7. https://pubmed.ncbi.nlm.nih.gov/8960881

264. Podrid PJ. Safety and toxicity of antiarrhythmic drug therapy: benefit versus risk. J Cardiovasc Pharmacol. 1991; 17(Suppl 6):S65-73. https://pubmed.ncbi.nlm.nih.gov/1723122

265. Hapke HJ, Prigge E. Pharmacology of 2′-[2-hydroxy-3-(propylamino)-propoxy]-3-phenylpropiophenone (Propafenone, SA 79)-hydrochloride. Arzneimittelforschung. 1976; 26:1849-57. https://pubmed.ncbi.nlm.nih.gov/1037204

266. Burgess ED, Duff HJ. Hemodialysis removal of propafenone. Pharmacotherapy. 1989; 9:331-3. https://pubmed.ncbi.nlm.nih.gov/2813154

267. Prystowsky EN, Benson W Jr, Fuster V et al. Management of patients with atrial fibrillation: a statement for healthcare professionals from the subcommittee on electrocardiography and electrophysiology, American Heart Association. Circulation. 1996; 93:1262-77. https://pubmed.ncbi.nlm.nih.gov/8653857

268. Falk RH. Flecainide-induced ventricular tachycardia and fibrillation in patients treated for atrial fibrillation. Ann Intern Med. 1989; 111:107-11. https://pubmed.ncbi.nlm.nih.gov/2500880

269. Kowey PR, Marinchak RA, Rials SJ et al. Acute treatment of atrial fibrillation. Am J Cardiol. 1998; 81:16C-22C. https://pubmed.ncbi.nlm.nih.gov/9525568

270. Kennedy HL, Whitlock JA, Sprague MK et al. Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy. N Engl J Med. 1985; 312:193-7. https://pubmed.ncbi.nlm.nih.gov/2578212

271. Van Gelder IC, Brugemann J, Crijns HJGM. Current treatment recommendations in antiarrhythmic therapy. Drugs. 1998; 55:331-46. https://pubmed.ncbi.nlm.nih.gov/9530541

272. Reviewers’ comments (personal observations).

273. Knoll Pharmaceutical Company, Mt. Olive, NJ: Personal communication.

274. Tartini R, Kappenberger L, Steinbrunn W et al. Gefahrliche Interaktionen zwischen Amiodaron und Antiarrhythmika der Klasse I. (German; with English abstract.) Schweiz Med Wochenschr. 1982; 112:1585-7. (amiodarone ref 264)

275. Ansell JE, Buttaro ML, Voltis Thomas O et al et al. Consensus guidelines for coordinated outpatient oral anticoagulation therapy management. Ann Pharmacother. 1997; 31:604-15. https://pubmed.ncbi.nlm.nih.gov/9161658

276. Woodland C, Verjee Z, Giesbrecht E et al. The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers. J Pharmacol Exp Ther. 1997; 283: 39-45. https://pubmed.ncbi.nlm.nih.gov/9336306

277. Woodland C, Ito S, Koren G. A model for the prediction of digoxin-drug interactions at the renal tubular cell level. Ther Drug Monit. 1998; 20:134-8. https://pubmed.ncbi.nlm.nih.gov/9558126

278. Nolan PE Jr, Marcus FI, Erstad BL et al. Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects. J Clin Pharmacol. 1989; 29:46-52. https://pubmed.ncbi.nlm.nih.gov/2708548

279. Belz GG, Doering W, Munkes R et al. Interaction between digoxin and calcium antagonists and antiarrhythmic drugs. Clin Pharmacol Ther. 1983; 33:410-7. https://pubmed.ncbi.nlm.nih.gov/6831819

280. Hii JT, Duff HJ, Burgess ED. Clinical pharmacokinetics of propafenone. Clin Pharmacokinet. 1991; 21:1-10. https://pubmed.ncbi.nlm.nih.gov/1914339

281. Koytchev R, Alken RG,; Mayer O. Effect of diprafenone on the pharmacokinetics of digoxin. Eur J Clin Pharmacol. 1996; 50:97-100. https://pubmed.ncbi.nlm.nih.gov/8739818

282. Palumbo E, Svetoni N, Casini M et al. [Digoxin-propafenone interaction: values and limitations of plasma determination of the 2 drugs. Anti-arrhythmia effectiveness of propafenone]. G Ital Cardiol. 1986; 16:855-62. https://pubmed.ncbi.nlm.nih.gov/3817368

283. Calvo MV, Martin-Suarez A, Martin Luengo C et al. Interaction between digoxin and propafenone. Ther Drug Monit. 1989; 11:10-5. https://pubmed.ncbi.nlm.nih.gov/2911842

284. Hodges M, Salerno D, Granrud G. Double-blind placebo-controlled evaluation of propafenone in suppressing ventricular etopic activity. Am J Cardiol. 1984; 54:45D-50D. https://pubmed.ncbi.nlm.nih.gov/6388303

285. Piscitelli SC, Flexner C, Minor JR et al. Drug interactions in patients infected with human immunodeficiency virus. Clin Infect Dis. 1996; 23:685-93. https://pubmed.ncbi.nlm.nih.gov/8909827

286. Abbott Laboratories. Norvir (ritonavir) capsules and oral solution prescribing information. North Chicago, IL; 1997 Mar.

287. Marcus FI. Drug interactions with amiodarone. Am Heart J. 1983; 106(4 Part 2):924-30. https://pubmed.ncbi.nlm.nih.gov/6137140

289. Reliant Pharmaceuticals, Inc. Rythmol SR (propafenone hydrochloride) extended-release capsules prescribing information. Liberty Corner, NJ; 2005 Dec.

290. Alboni P, Botto GL, Baldi Net al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket” approach. N Engl J Med. 2004; 351:2384-91. https://pubmed.ncbi.nlm.nih.gov/15575054

291. Gronefeld GC, Hohnloser SH. The “pill-in-the-pocket” approach to atrial fibrillation.N Engl J Med. 2005; 352:1150. Letter. https://pubmed.ncbi.nlm.nih.gov/15784671

292. Konety SH, Olshansky B. The “pill-in-the-pocket” approach to atrial fibrillation.N Engl J Med. 2005; 352:1150. Letter. https://pubmed.ncbi.nlm.nih.gov/15789457

293. Wittkowsky AK. The “pill-in-the-pocket” approach to atrial fibrillation.N Engl J Med. 2005; 352:1150-1. Letter. https://pubmed.ncbi.nlm.nih.gov/15789456

294. Alboni P, Botto GI, Baldi N. The “pill-in-the-pocket” approach to atrial fibrillation.N Engl J Med. 2005; 352:1151. Reply.

295. Botto GL, Capucci A, Bonini W et al. Conversion of recent onset atrial fibrillation to sinus rhythm using a single oral loading dose of propafenone: comparison of two regimens. Int J Cardiol. 1997; 58:55-61. https://pubmed.ncbi.nlm.nih.gov/9021428

296. Boriani G, Biffi M, Capucci A et al. Oral propafenone to convert recent-onset atrial fibrillation in patients with and without underlying heart disease. A randomized, controlled trial. Ann Intern Med. 1997; 126:621-5. https://pubmed.ncbi.nlm.nih.gov/9103129

297. Azpitarte J, Alvarez M, Baun O et al. Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study. Eur Heart J. 1997; 18:1649-54. https://pubmed.ncbi.nlm.nih.gov/9347277

298. Boriani G, Biffi M, Capucci A et al. Oral loading with propafenone: a placebo-controlled study in elderly and nonelderly patients with recent onset atrial fibrillation. Pacing Clin Electrophysiol. 1998; 21(11 Pt 2):2465-9. https://pubmed.ncbi.nlm.nih.gov/9825368

299. Boriani G, Biffi M, Capucci A et al. Conversion of recent-onset atrial fibrillation to sinus rhythm: effects of different drug protocols. Pacing Clin Electrophysiol. 1998; 21(11 Pt 2):2470-4. https://pubmed.ncbi.nlm.nih.gov/9825369

300. Capucci A, Villani GQ, Aschieri D et al. Safety of oral propafenone in the conversion of recent onset atrial fibrillation to sinus rhythm: a prospective parallel placebo-controlled multicentre study. Int J Cardiol. 1999; 68:187-96. https://pubmed.ncbi.nlm.nih.gov/10189007

301. Alboni P, Tomasi C, Menozzi C et al. Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia. J Am Coll Cardiol. 2001; 37:548-53. https://pubmed.ncbi.nlm.nih.gov/11216977

302. Capucci A, Lenzi T, Boriani G et al. Effectiveness of loading oral flecainide for converting recent-onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension. Am J Cardiol. 1992; 70:69-72. https://pubmed.ncbi.nlm.nih.gov/1615873

303. Blanc JJ, Voinov C, Maarek M. Comparison of oral loading dose of propafenone and amiodarone for converting recent-onset atrial fibrillation. PARSIFAL Study Group. Am J Cardiol. 1999; 84:1029-32. https://pubmed.ncbi.nlm.nih.gov/10569658

304. Khan IA. Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol. 2001; 37:542-7. https://pubmed.ncbi.nlm.nih.gov/11216976

305. Boriani G, Martignani C, Biffi M et al. Oral loading with propafenone for conversion of recent-onset atrial fibrillation: a review on in-hospital treatment. Drugs. 2002; 62:415-23. https://pubmed.ncbi.nlm.nih.gov/11827557

306. Khan IA. Oral loading single dose flecainide for pharmacological cardioversion of recent-onset atrial fibrillation. Int J Cardiol. 2003; 87:121-8. https://pubmed.ncbi.nlm.nih.gov/12559528

307. Deneer VH, Borgh MB, Kingma JH et al.Oral antiarrhythmic drugs in converting recent onset atrial fibrillation. Pharm World Sci. 2004; 26:66-78. https://pubmed.ncbi.nlm.nih.gov/15085940

308. Reliant Pharmaceuticals, Inc. Product information (RYTH-4002) for Rythmol SR (propafenone hydrochloride) extended-release capsules. Liberty Corner, NJ; 2004 Jan.

309. Reviewers’ comments (personal observations).

310. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

700. Page RL, Joglar JA, Caldwell MA et al. 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2016; 67:e27-e115.

701. January CT, Wann LS, Alpert JS et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014; 64:e1-76. https://pubmed.ncbi.nlm.nih.gov/24685669