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Pronunciation: proe-pa-FEEN-one
Class: Antiarrhythmic agent

Trade Names

- Tablets, immediate-release 300 mg

- Tablets, immediate-release 150 mg
- Tablets, immediate-release 225 mg

Rythmol SR
- Capsule, extended-release 225 mg
- Capsule, extended-release 325 mg
- Capsule, extended-release 425 mg

Apo-Propafenone (Canada)
Gen-Propafenone (Canada)


Reduces fast inward current carried by sodium ion in the Purkinje fibers, and to a lesser extent the myocardial fibers.

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Nearly completely absorbed. T max is approximately 3.5 h for immediate-release (IR) and approximately 3 to 8 h for extended-release (ER). Bioavailability is dose- and dosage-form dependent and is 3.4% (150 mg), 10.6% (300 mg), and 21.4% (300 mg solution). Steady state is 4 to 5 days. Food increased peak blood levels and bioavailability in single dose study; however, multiple doses did not change bioavailability significantly.


Protein binding is greater than 95%. Propafenone and 5-hydroxypropafenone are distributed into breast milk. Total Vd is about 252 L.


Exhibits extensive first-pass metabolism in the liver producing 2 main active metabolites: 5-hydroxypropafenone and n-depropylpropafenone, which have antiarrhythmic activity comparable with propafenone, but present in concentrations less than 20%. Two genetically metabolism groups exist: fast and slow metabolizers; 90% are fast and 10% are slow metabolizers.


Renal (38% as metabolites, less than 1% as unchanged); fecal (53% as metabolites). The half-life is 2 to 10 h (rapid metabolizers); 10 to 32 h (slower metabolizers).

Special Populations

Hepatic Function Impairment

Cl is reduced and elimination half-life is increased.

Indications and Usage


Prolonged time to recurrence of paroxysmal atrial fibrillation/flutter or paroxysmal supraventricular tachycardia associated with disabling symptoms in patients without structural heart disease; treatment of ventricular arrhythmias (eg, sustained ventricular tachycardia [VT]) that are life-threatening.


Prolong the time to recurrence of symptomatic atrial fibrillation in patients with structural heart disease.


Uncontrolled CHF; cardiogenic shock; sinoatrial, AV, and intraventricular disorders of impulse generation and/or conduction (eg, sick sinus node syndrome, AV block) in the absence of an artificial pacemaker; bradycardia; marked hypotension; bronchospastic disorders; manifest electrolyte imbalance; known hypersensitivity to the drug.

Dosage and Administration

Individually titrate dose based on response and tolerance.


PO (IR) 150 mg every 8 h initially, increasing at a minimum of 3- to 4-day intervals to 225 mg every 8 h and, if necessary, to 300 mg every 8 h.


PO (ER) 225 mg every 12 h initially, increasing at a minimum of 5-day intervals to 325 mg every 12 h (max, 425 mg every 12 h).

General Advice

  • IR tablet
  • Administer without regard to meals but administer with food if GI upset occurs.
  • Do not increase dose more often than every 3 days during dosage titration as optimal effect may not be achieved during the first 3 days following initiation of therapy or dose change.
  • ER capsule
  • Caution patient to swallow capsule whole and not to chew, crush, or open the capsule.
  • Administer without regard to meals but administer with food if GI upset occurs.
  • Do not increase dose more often than every 5 days during dosage titration as optimal effect may not be achieved during the first 5 days following initiation of therapy or dose change.


Store IR tablets and ER capsules at controlled room temperature (59° to 86°F).

Drug Interactions

Cimetidine, certain serotonin reuptake inhibitors (eg, fluoxetine, paroxetine, sertraline), quinidine, ritonavir

May increase propafenone plasma concentrations, potentially increasing pharmacologic effects and adverse reactions.

Cyclosporine, desipramine, digoxin, metoprolol, propranolol, theophylline, venlafaxine, warfarin

Propafenone may increase plasma concentrations of these agents, increasing the risk of adverse reactions and toxicity.

Drugs that prolong the QT interval (eg, cisapride, bepridil, tricyclic antidepressants), antiarrhythmic agents (class Ia and III antiarrhythmic agents [eg, amiodarone, quinidine])

Coadministration with propafenone is not recommended because of the increased risk of life-threatening cardiac arrhythmias. Ensure class Ia or III antiarrhythmic has been withheld for at least 5 half-lives before initiating therapy with propafenone.

Local anesthetics

May increase the risk of CNS adverse reactions.


Mexiletine metabolism may be inhibited, elevating plasma levels in extensive metabolizers and increasing the risk of adverse reactions.

Rifamycins (eg, rifabutin, rifapentine)

May decrease propafenone plasma concentrations, decreasing the therapeutic effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Angina, proarrhythmia (5%); CHF (4%); first-degree AV block, palpitation, VT (3%); PVCs, increased QRS duration, syncope, bradycardia, chest pain, weakness (2%); bundle branch block, atrial fibrillation, hypotension, intraventricular conduction delay (1%); atrial flutter, AV dissociation, cardiac arrest, sick sinus syndrome, sinus pause or arrest, supraventricular tachycardia, prolongation of PR and QRS intervals (less than 1%).


Dizziness (13%); fatigue (6%); headache (5%); insomnia, anorexia, anxiety, ataxia (2%); drowsiness, tremor (1%).


Rash (3%).


Blurred vision (4%).


Nausea and vomiting (11%); unusual taste (9%); constipation (7%); diarrhea, dyspepsia (3%); dry mouth, abdominal pain, cramps (2%); flatulence (1%).


Agranulocytosis, anemia, bruising, granulocytopenia, leukopenia, thrombocytopenia.


Joint pain (1%).


Dyspnea (5%); edema, diaphoresis (1%).



Mortality risks noted for flecainide and/or encainide (type 1C antiarrhythmics). Reserved for use in patients with life-threatening ventricular arrhythmias.



Assess CBC with differential before starting therapy and periodically thereafter during prolonged treatment.

Renal function

Assess renal function (BUN, serum creatinine) and liver enzymes before initiating therapy and periodically thereafter during long-term treatment.


Category C .


Excreted in breast milk.


Safety and efficacy not established.


Because of the increased risk of impaired renal and hepatic function, use with caution.

Renal Function

Use with caution.

Hepatic Function

Use with caution.

Antinuclear antibody (ANA) titers

Positive ANA titers may occur.

CV effects

Has proarrhythmic effect; evaluate patients electrocardiographically and clinically prior to and during therapy to determine if response supports continued use.


Because propafenone exerts beta-blockade and a negative inotropic effect, fully compensate patients before giving propafenone.

Conduction disturbances

Dose-related first degree AV block, average PR interval prolongation, and increases in QRS duration may occur.

Nonallergic bronchospasm

Avoid propafenone administration.

Pacemaker threshold

Pacing and sensing thresholds of artificial pacemakers may be altered. Ensure pacing threshold is determined before starting therapy, and periodically thereafter, in patient with pacemaker.



Hypotension, somnolence, bradycardia, intra-atrial and intraventricular conduction disturbances, convulsions, high-grade ventricular arrhythmias.

Patient Information

  • Advise patient that dose of medication will be changed periodically to obtain max benefit.
  • Caution patient taking ER capsules to take prescribed dose every 12 h exactly as ordered.
  • Caution patient taking IR tablets to take prescribed dose every 8 h exactly as ordered.
  • Caution patient that serious heart disturbances can result from missing doses.
  • Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
  • Caution patient not to change the dose or stop taking unless advised by health care provider. Advise patient that serious adverse reactions can result from increasing or decreasing the dose without medical supervision.
  • Advise patient that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up.
  • Inform patient that drug controls, but does not cure, abnormal heart rhythm and to continue taking as prescribed once the heart rhythm has been controlled.
  • Instruct patient to continue taking other heart medications as prescribed by health care provider.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Advise patient with heart failure or those taking other medications with negative inotropic effect to monitor and record weight on a daily basis, and to inform health care provider if unexplained or rapid weight gain is noted.
  • Instruct patient to lie or sit down if they experience dizziness or lightheadedness when standing.
  • Advise patient to notify health care provider if any of the following occur: frequent episodes of dizziness or lightheadedness, persistent fatigue, persistent headache, constipation, vision changes, any other unusual or unexplained symptom or sign.
  • Instruct patient to immediately report the following to health care provider: fainting, pounding in chest, new or worsening shortness of breath, change in pulse or heart rhythm, swelling in feet or ankles, any symptom affecting electrolyte balance (eg, excessive or prolonged diarrhea, excessive sweating, vomiting), any sign or symptom of infection (eg, fever, sore throat, chills), bleeding, or unusual bruising.
  • Caution patient that drug may cause dizziness or drowsiness and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Advise patient to carry medical identification (eg, card, bracelet) describing cardiac condition and medication regimen.
  • Offer family instruction in basic life support.

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