pharmacopeia
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/api/v1/drug/propafenone

Boxed warning

MORTALITY In the National Heart, Lung, and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind trial in subjects with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than 6 days but less than 2 years previously, an increased rate of death or reversed cardiac arrest rate (7.7%; 56/730) was seen in subjects treated with encainide or flecainide (Class IC antiarrhythmics) compared with that seen in subjects assigned to placebo (3.0%; 22/725). The average duration of treatment with encainide or flecainide in this trial was 10 months. The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) or other antiarrhythmic drugs is uncertain, but at present, it is prudent to consider any IC antiarrhythmic to have a significant proarrhythmic risk in patients with structural heart disease. Given the lack of any evidence that these drugs improve survival, antiarrhythmic agents should generally be avoided in patients with non-life-threatening ventricular arrhythmias, even if the patients are experiencing unpleasant, but not life-threatening, symptoms or signs. WARNING: MORTALITY See full prescribing information for complete boxed warning.

2D structure
1-[2-[2-hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylpropan-1-one
SMILES CCCNCC(COC1=CC=CC=C1C(=O)CCC2=CC=CC=C2)O
InChIKey JWHAUXFOSRPERK-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects and a direct stabilizing action on myocardial membranes. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential.

Indications

Sourced from openFDA
  • Propafenone hydrochloride tablets are indicated to: prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. prolong the time to recurrence of paroxysmal supraventricular tachycardia (PSVT) associated with disabling symptoms in patients without structural heart disease.ICD-10: I48.91

Contraindications

Sourced from openFDA
  • Propafenone hydrochloride tablets are contraindicated in the following circumstances: Heart failure Cardiogenic shock Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or conduction (e.g., sick sinus node syndrome, AV block) in the absence of an artificial pacemaker Known Brugada Syndrome Bradycardia Marked hypotension Bronchospastic disorders or severe obstructive pulmonary disease Marked electrolyte imbalance Heart failure (4) Cardiogenic shock (4) Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or conduction in the absence of pacemaker (4) Known Brugada Syndrome (4) Bradycardia (4) Marked hypotension (4) Bronchospastic disorders and severe obstructive pulmonary disease (4) Marked electrolyte imbalance (4)contraindicated

Dosage & administration

Sourced from openFDA

The dose of propafenone hydrochloride tablets must be individually titrated on the basis of response and tolerance. Initiate therapy with propafenone hydrochloride tablets 150 mg given every 8 hours (450 mg per day). Dosage may be increased at a minimum of 3- to 4- day intervals to 225 mg every 8 hours (675 mg per day). If additional therapeutic effect is needed, the dose of propafenone hydrochloride tablets may be increased to 300 mg every 8 hours (900 mg per day). The usefulness and safety of dosages exceeding 900 mg per day have not been established. In patients with hepatic impairment or those with significant widening of the QRS complex or second- or third-degree AV block, consider reducing the dose. As with other antiarrhythmic agents, in the elderly or in ventricular arrhythmia patients with marked previous myocardial damage, the dose of propafenone hydrochloride tablets should be increased more gradually during the initial phase of treatment. The combination of cytochrome P450 3A4 (CYP3A4) inhibition and either cytochrome P450 2D6 (CYP2D6) deficiency or CYP2D6 inhibition with the simultaneous administration of propafenone may significantly increase the concentration of propafenone and thereby increase the risk of proarrhythmia and other adverse events. Therefore, avoid simultaneous use of propafenone hydrochloride tablets with both a CYP2D6 inhibitor and a CYP3A4 inhibitor [see Warnings and Precautions (5.4) , Drug Interactions (7.1) ] . Initiate therapy with 150 mg given every 8 hours. (2) As needed, uptitrate in 3 to 4 days to 225 to 300 mg every 8 hours.

Warnings & precautions

Sourced from openFDA

May cause new or worsened arrhythmias. Evaluate patients via ECG prior to and during therapy. (5.1) Propafenone hydrochloride may unmask Brugada or Brugada-like Syndrome. (4 , 5.2) Avoid use with other drugs that prolong the QT interval. (5.3) Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). (5.4) May provoke overt heart failure. (5.5) May cause dose-related first-degree AV block or other conduction disturbances. Only use in patients with conduction disorders who have pacemakers. (5.6) May affect artificial pacemakers. Monitor pacemaker function. (5.7) Agranulocytosis: Patients should report signs of infection. (5.8) May exacerbate myasthenia gravis. (5.11) 5.1 Proarrhythmic Effects Propafenone has caused new or worsened arrhythmias. Such proarrhythmic effects include sudden death and life-threatening ventricular arrhythmias such as ventricular fibrillation, ventricular tachycardia, asystole, and torsade de pointes. It may also worsen premature ventricular contractions or supraventricular arrhythmias, and it may prolong the QT interval. It is therefore essential that each patient given propafenone hydrochloride be evaluated electrocardiographically prior to and during therapy to determine whether the response to propafenone hydrochloride supports continued treatment. Because propafenone prolongs the QRS interval in the electrocardiogram, changes in the QT interval are difficult to interpret [see Clinical Pharmacology (12.2) ]. In a U.S.

Adverse reactions

Sourced from openFDA

The most commonly reported adverse events with propafenone (greater than 5%) included: unusual taste, nausea and/or vomiting, dizziness, constipation, headache, fatigue, first-degree AV block, and intraventricular conduction delay. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions associated with propafenone hydrochloride occur most frequently in the gastrointestinal, cardiovascular, and central nervous systems. About 20% of subjects treated with propafenone hydrochloride have discontinued treatment because of adverse reactions. Adverse reactions reported for greater than 1.5% of 474 subjects with SVT who received propafenone hydrochloride in U.S. clinical trials are presented in Table 1 by incidence and percent discontinuation, reported to the nearest percent. Table 1.

Use in specific populations

Sourced from openFDA

8.1 Pregnancy Risk Summary There are no studies of propafenone hydrochloride in pregnant women. Available data from published case reports and several decades of postmarketing experience with use of propafenone hydrochloride in pregnancy have not identified any drug-associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. Untreated arrhythmias during pregnancy may pose a risk to the pregnant woman and fetus (see Clinical Considerations). Propafenone and its metabolite, 5-OH-propafenone, cross the placenta in humans. In animal studies, propafenone was not teratogenic. At maternally toxic doses (ranging from 2 to 6 times the maximum recommended human dose [MRHD]), there was evidence of adverse developmental outcomes when administered to pregnant rabbits and rats during organogenesis or when administered to pregnant rats during mid-gestation through weaning of their offspring (see Data) . The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Pharmacokinetics

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

Overdosage

Sourced from openFDA

The symptoms of overdosage may include hypotension, somnolence, bradycardia, intra-atrial and intraventricular conduction disturbances, and rarely, convulsions and high-grade ventricular arrhythmias. Defibrillation, as well as infusion of dopamine and isoproterenol, has been effective in controlling abnormal rhythm and blood pressure. Convulsions have been alleviated with intravenous diazepam. General supportive measures such as mechanical respiratory assistance and external cardiac massage may be necessary. The hemodialysis of propafenone in patients with an overdose is expected to be of limited value in the removal of propafenone as a result of both its high protein binding (greater than 95%) and large volume of distribution.

Approval history

Sourced from openFDA
  • Oct 24, 2000ANDAANDA075203Watson Labs
  • Oct 17, 2002ANDAANDA075938Strides Pharma Intl
  • Apr 23, 2004ANDAANDA076550Ani Pharms
  • Oct 18, 2010ANDAANDA078540Strides Pharma Intl
  • May 11, 2016ANDAANDA202445Aurobindo Pharma
  • Sep 8, 2017ANDAANDA205268Glenmark Pharms Ltd
  • Jul 2, 2018ANDAANDA205956Rising
  • Jan 4, 2019ANDAANDA210339Sinotherapeutics Inc

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
5,399 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Atrial Fibrillation4859.0%
  2. 2Drug Ineffective3907.2%
  3. 3Drug Interaction3807.0%
  4. 4Dizziness3646.7%
  5. 5Dyspnoea3075.7%
  6. 6Nausea2925.4%
  7. 7Fatigue2845.3%
  8. 8Toxicity To Various Agents2564.7%
  9. 9Hypotension2534.7%
  10. 10Asthenia2514.6%
  11. 11Bradycardia2164.0%
  12. 12Diarrhoea2043.8%
  13. 13Fall2033.8%
  14. 14Off Label Use2033.8%
  15. 15Arrhythmia1933.6%

Literature

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Recent PubMed references pinned to Propafenone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 53 ClinicalTrials.gov registrations naming Propafenone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Propafenone. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

  • CYP2D6CPIC B/C (provisional)ClinPGx 1AFDA label: No Clinical PGx

Frequently asked questions

How does Propafenone work?
Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects and a direct stabilizing action on myocardial membranes. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential.
What is Propafenone used for?
According to FDA labeling, Propafenone carries indications including: Propafenone hydrochloride tablets are indicated to: prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. prolong the time to recurrence of paroxysmal supraventricular tachycardia (PSVT) associated with disabling symptoms in patients without structural heart disease.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Propafenone?
Propafenone is classified as Antiarrhythmics, class Ic, Antiarrhythmic, Adrenergic beta-Antagonists, Sodium Channel Interactions, Decreased Cardiac Muscle Organized Electrical Activity, Local Anesthesia, Negative Chronotropy.
What are the brand names for Propafenone?
Propafenone is marketed under brand names including Rythmol.
What are the contraindications for Propafenone?
Propafenone labeling lists contraindications including: Propafenone hydrochloride tablets are contraindicated in the following circumstances: Heart failure Cardiogenic shock Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or conduction (e.g., sick sinus node syndrome, AV block) in the absence of an artificial pacemaker Known Brugada Syndrome Bradycardia Marked hypotension Bronchospastic disorders or severe obstructive pulmonary disease Marked electrolyte imbalance Heart failure (4) Cardiogenic shock (4) Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or conduction in the absence of pacemaker (4) Known Brugada Syndrome (4) Bradycardia (4) Marked hypotension (4) Bronchospastic disorders and severe obstructive pulmonary disease (4) Marked electrolyte imbalance (4). Always consult the full prescribing information and a clinician.
Note. Data for propafenone is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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