Propafenone Hydrochloride 325 mg Capsule, Extended Release, 60-count
Other active recalls for Propafenone Hydrochloride (different manufacturers) — 4 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Antiarrhythmic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Think of it as an electrical 'slow-down' for your heart. Your heart has channels that carry electrical signals triggering each beat — propafenone partially blocks those channels so...
- What exactly is propafenone doing for my heart?
- Yes, a few important ones. Grapefruit juice can raise propafenone levels in your blood, so it's best to avoid it. Several medications — including some antidepressants like paroxeti...
- Are there foods or common medications I should avoid while taking this?
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.9500 | $57.00 / 60 capsules |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Propafenone Hydrochloride 325 mg 00832-0741-60 | Upsher-Smith | 60 capsules | $0.530 | AB | Availability likely | — |
| Propafenone Hydrochloride 325 mg 16571-0737-06 | Rising | 60 capsules | $0.530 | AB | Availability likely | — |
| propafenone hydrochloride 325 mg 16714-0826-01 | Northstar | 60 capsules | $0.530 | AB | Availability likely | — |
| Propafenone Hydrochloride 325 mg 64380-0185-01 | Strides | 60 capsules | $0.530 | AB | Discontinued | — |
| propafenone hydrochloride 325 mg 68462-0409-60 | Glenmark | 60 capsules | $0.530 | AB | Availability likely | — |
| Propafenone Hydrochloride 325 mg 69680-0131-60 | Vitruvias | 60 capsules | $0.530 | AB | Availability likely | — |
| Propafenone Hydrochloride 325 mg 59651-0277-05 | Aurobindo | 500 capsules | — | AB | FDA listed | — |
| Propafenone Hydrochloride 325 mgthis 68382-0523-14 | Zydus | 60 capsules | — | AB | FDA listed | — |
| Propafenone Hydrochloride 325 mg 70771-1526-05 | Zydus | 500 capsules | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68382-0523-05 | 500 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (68382-523-05) | 2022-02-02 | Active |
| 68382-0523-14 You're viewing this | 60 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (68382-523-14) | 2022-02-02 | Active |
You're viewing the smallest of 2 pack sizes for this product.
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: MORTALITY In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind trial in patients 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 patients treated with encainide or flecainide (Class IC antiarrhythmics) compared with that seen in patients assigned to placebo (3%; 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. An increased rate of death or reversed cardiac arrest rate was seen in patients treated with encainide or flecainide (Class IC antiarrhythmics) compared with that seen in patients assigned to placebo. At present, it is prudent to consider any IC antiarrhythmic to have a significant risk of provoking proarrhythmic events 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.
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Propafenone hydrochloride extended-release capsules are indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. Usage Considerations: The use of propafenone hydrochloride extended-release capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use propafenone hydrochloride extended-release capsules to control ventricular rate during AF.
Some patients with atrial flutter treated with propafenone have developed 1:1 conduction, producing an increase in ventricular rate. Concomitant treatment with drugs that increase the functional atrioventricular (AV) nodal refractory period is recommended. The effect of propafenone on mortality has not been determined [see Boxed Warning] .
Propafenone hydrochloride extended-release capsules are an antiarrhythmic indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. (1) Usage Considerations: Use in patients with permanent atrial fibrillation or with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use to control ventricular rate during atrial fibrillation.
(1) In patients with atrial fibrillation and atrial flutter, use propafenone hydrochloride extended-release capsules with drugs that increase the atrioventricular nodal refractory period. (1) The effect of propafenone on mortality has not been determined. (1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Propafenone hydrochloride extended-release capsules can be taken with or without food. Do not crush or further divide the contents of the capsule. The dose of propafenone hydrochloride extended-release capsules must be individually titrated on the basis of response and tolerance.
Initiate therapy with propafenone hydrochloride extended-release capsules 225 mg given every 12 hours. Dosage may be increased at a minimum of 5-day intervals to 325 mg given every 12 hours. If additional therapeutic effect is needed, the dose of propafenone hydrochloride extended-release capsules may be increased to 425 mg given every 12 hours.
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. 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 extended-release capsules with both a CYP2D6 inhibitor and a CYP3A4 inhibitor [see Warnings and Precautions ( 5.4 ), Drug Interactions ( 7.1 )] .
Initiate therapy with 225 mg given every 12 hours. (2) Dosage may be increased at a minimum of 5-day intervals to 325 mg every 12 hours and, if necessary, to 425 mg every 12 hours. (2) Consider reducing the dose in patients with hepatic impairment, significant widening of the QRS complex, or second- or third-degree AV block.
(2)
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Propafenone hydrochloride extended-release capsules, USP are supplied as hard gelatin capsules containing 225 mg, 325 mg or 425 mg of propafenone hydrochloride, USP. The 225 mg capsule has a white to off-white minitablets filled in the size "1" empty hard gelatin capsules having white opaque colored cap and white opaque colored body imprinted with '522' in black ink. The 325 mg capsule has a white to off-white minitablets filled in the size "0" empty hard gelatin capsules having pink opaque colored cap and white opaque colored body imprinted with '523' in black ink.
The 425 mg capsule has a white to off-white minitablets filled in the size "0el" empty hard gelatin capsules having red opaque colored cap and white opaque colored body imprinted with '524' in black ink. Capsules: 225 mg, 325 mg, 425 mg. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Propafenone hydrochloride extended-release capsules 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 and/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)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS May cause new or worsened arrhythmias. Evaluate patients via ECG prior to and during therapy. ( 5.1 ) Propafenone hydrochloride extended-release capsules may unmask Brugada or Brugada-like Syndrome.
Evaluate patients via ECG after initiation of therapy. ( 4 , 5.2 ) Avoid use with other antiarrhythmic agents or 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. Should not be given to patients with conduction defects in absence of a pacemaker.
( 5.6 ) May affect artificial pacemakers. Pacemakers should be monitored during therapy. ( 5.7 ) Agranulocytosis: Patients should report signs of infection.
( 5.8 ) Administer cautiously to patients with impaired hepatic and renal function. ( 5.9 , 5.10 ) Exacerbation of myasthenia gravis has been reported. ( 5.11 )
5.1Proarrhythmic 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 extended-release capsules be evaluated electrocardiographically prior to and during therapy to determine whether the response to propafenone hydrochloride extended-release capsules 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 the propafenone hydrochloride extended-release capsules Atrial Fibrillation Trial (RAFT) trial [see Clinical Studies ( 14 )] , there were too few deaths to assess the long-term risk to patients.
There were 5 deaths, 3 in the pooled group for propafenone hydrochloride extended-release capsules (0.8%), and 2 in the placebo group (1.6%). In the overall database of 8 trials of propafenone hydrochloride extended-release capsules and propafenone hydrochloride immediate-release, the mortality rate was 2.5% per year on propafenone and 4% per year on placebo. Concurrent use of propafenone with other antiarrhythmic agents has not been well studied.
In a U.S. uncontrolled, open-label, multicenter trial using the immediate-release formulation in patients with symptomatic supraventricular tachycardia (SVT), 1.9% (9/474) of these patients experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) during the trial. However, in 4 of the 9 patients, the ventricular tachycardia was of atrial origin. Six of the 9 patients that developed ventricular arrhythmias did so within 14 days of onset of therapy.
About 2.3% (11/474) of all patients had recurrence of SVT during the trial which could have been a change in the patients' arrhythmia behavior or could represent a proarrhythmic event. Case reports in patients treated with propafenone for atrial fibrillation/flutter have included increased premature ventricular contractions (PVCs), VT, VF, torsades de pointes, asystole, and death. Overall in clinical trials with propafenone hydrochloride immediate-release (which included patients treated for ventricular arrhythmias, atrial fibrillation/flutter, and PSVT), 4.7% of all patients had new or worsened ventricular arrhythmia possibly representing a proarrhythmic event (0.7% was an increase in PVCs; 4% a worsening or new appearance of VT or VF).
Of the patients who had worsening of VT (4%), 92% had a history of VT and/or VT/VF, 71% had coronary artery disease, and 68% had a prior myocardial infarction. The incidence of proarrhythmia in patients with less serious or benign arrhythmias, which include patie…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most commonly reported adverse events with propafenone (greater than 5% and greater than placebo) excluding those not reasonably associated with the use of the drug included the following: dizziness, palpitations, chest pain, dyspnea, taste disturbance, nausea, fatigue, anxiety, constipation, upper respiratory tract infection, edema, and influenza. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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. The data described below reflect exposure to propafenone hydrochloride extended-release capsules 225 mg twice daily in 126 patients, to propafenone hydrochloride extended-release capsules 325 mg twice daily in 135 patients, to propafenone hydrochloride extended-release capsules 425 mg twice daily in 136 patients, and to placebo in 126 patients for up to 39 weeks (mean: 20 weeks) in a placebo-controlled trial (RAFT) conducted in the U.S.
The most commonly reported adverse events with propafenone (greater than 5% and greater than placebo) excluding those not reasonably associated with the use of the drug or because they were associated with the condition being treated, were dizziness, palpitations, chest pain, dyspnea, taste disturbance, nausea, fatigue, anxiety, constipation, upper respiratory tract infection, edema, and influenza. The frequency of discontinuation due to adverse events was 17%, and the rate was highest during the first 14 days of treatment.
Cardiac-related adverse events occurring in greater than or equal to 2% of the patients in any of the RAFT propafenone extended-release treatment groups and more common with propafenone than with placebo, excluding those that are common in the population and those not plausibly related to drug therapy, included the following: angina pectoris, atrial flutter, AV block first-degree, bradycardia, congestive cardiac failure, cardiac murmur, edema, dyspnea, rales, wheezing, and cardioactive drug level above therapeutic. Propafenone prolongs the PR and QRS intervals in patients with atrial and ventricular arrhythmias.
Prolongation of the QRS interval makes it difficult to interpret the effect of propafenone on the QT interval [see Clinical Pharmacology ( 12.2 )]. Non-cardiac related adverse events occurring in greater than or equal to 2% of the patients in any of the RAFT propafenone extended-release treatment groups and more common with propafenone than with placebo, excluding those that are common in the population and those not plausibly related to drug therapy, included the following: blurred vision, constipation, diarrhea, dry mouth, flatulence, nausea, vomiting, fatigue, weakness, upper respiratory tract infection, blood alkaline phosphatase increased, hematuria, muscle weakness, dizziness (excluding vertigo), headache, taste disturbance, tremor, somnolence, anxiety, depression, ecchymosis.
No clinically important differences in incidence of adverse reactions were noted by age or gender. Too few non-Caucasian patients were enrolled to assess adverse events according to race. Adverse events occurring in 2% or more of the patients in any of the ERAFT [see Clinical Studies ( 14 )] propafenone extended-release treatment groups and not listed above include the following: bundle branch block left, bundle branch block right, conduction disorders, sinus bradycardia, and hypotension.
Other adverse events reported with propafenone clinical trials not already listed elsewhere in the prescribing information include the following adverse events by body system and preferred term. Blood and Lymphatic System Anemia, lymphadenopathy, spleen disorder, thrombocytopenia. Cardiac Uns…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Inhibitors of CYP2D6, 1A2, and 3A4 may increase propafenone levels which may lead to cardiac arrhythmias. Simultaneous use with both a CYP3A4 and CYP2D6 inhibitor (or in patients with CYP2D6 deficiency) should be avoided. ( 7.1 ) Propafenone may increase digoxin or warfarin levels.
( 7. 2, 7.3 ) Orlistat may reduce propafenone concentrations. Abrupt cessation of orlistat in patients stable on propafenone hydrochloride extended-release capsules has resulted in convulsions, atrioventricular block, and circulatory failure.
( 7.4 ) Concomitant use of lidocaine may increase central nervous system side effects. ( 7.6 )
7.1CYP2D6 and CYP3A4 Inhibitors Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin, grapefruit juice) can be expected to cause increased plasma levels of propafenone. The combination of CYP3A4 inhibition and either CYP2D6 deficiency or CYP2D6 inhibition with administration of propafenone may increase the risk of adverse reactions, including proarrhythmia. Therefore, simultaneous use of propafenone hydrochloride extended-release capsules with both a CYP2D6 inhibitor and a CYP3A4 inhibitor should be avoided [see Warnings and Precautions (5.4), Dosage and Administration (2)].
Amiodarone Concomitant administration of propafenone and amiodarone can affect conduction and repolarization and is not recommended. Cimetidine Concomitant administration of propafenone immediate-release tablets and cimetidine in 12 healthy subjects resulted in a 20% increase in steady-state plasma concentrations of propafenone. Fluoxetine Concomitant administration of propafenone and fluoxetine in extensive metabolizers increased the S-propafenone C max and AUC by 39% and 50%, respectively, and the R-propafenone C max and AUC by 71% and 50%, respectively.
Quinidine Small doses of quinidine completely inhibit the CYP2D6 hydroxylation metabolic pathway, making all patients, in effect, slow metabolizers [see Clinical Pharmacology (12.3)] . Concomitant administration of quinidine (50 mg 3 times daily) with 150 mg immediate-release propafenone 3 times daily decreased the clearance of propafenone by 60% in extensive metabolizers, making them poor metabolizers. Steady-state plasma concentrations increased by more than 2-fold for propafenone and decreased 50% for 5-OH-propafenone.
A 100 mg dose of quinidine increased steady-state concentrations of propafenone 3-fold. Avoid concomitant use of propafenone and quinidine. Rifampin Concomitant administration of rifampin and propafenone in extensive metabolizers decreased the plasma concentrations of propafenone by 67% with a corresponding decrease of 5-OH-propafenone by 65%.
The concentrations of norpropafenone increased by 30%. In poor metabolizers, there was a 50% decrease in propafenone plasma concentrations and an increase in the AUC and C max of norpropafenone by 74% and 20%, respectively. Urinary excretion of propafenone and its metabolites decreased significantly.
Similar results were noted in elderly patients: Both the AUC and C max of propafenone decreased by 84%, with a corresponding decrease in AUC and C max of 5-OH-propafenone by 69% and 57%, respectively.
7.2Digoxin Concomitant use of propafenone and digoxin increased steady-state serum digoxin exposure (AUC) in patients by 60% to 270% and decreased the clearance of digoxin by 31% to 67%. Monitor plasma digoxin levels of patients receiving propafenone and adjust digoxin dosage as needed.
7.3Warfarin The concomitant administration of propafenone and warfarin increased warfarin plasma concentrations at steady state by 39% in healthy volunteers and prolonged the prothrombin time (PT) in patients taking warfarin. Adjust the warfarin dose as needed by monitoring INR (international normalized ratio).
7.4Orlistat Orlistat may limit the fraction of propafenone available for absorption. In postmarketing reports, abrupt cessation of o…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary In the absence of studies in pregnant women, available data from published case reports and several decades of postmarketing experience with use of propafenone hydrochloride extended-release capsules 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. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk: The incidence of VT is increased and may be more symptomatic during pregnancy.
Ventricular arrhythmias most often occur in pregnant women with underlying cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse. Breakthrough arrhythmias may also occur during pregnancy, as therapeutic treatment levels may be difficult to maintain due to the increased volume of distribution and increased drug metabolism inherent in the pregnant state. Fetal/Neonatal Adverse Reactions: Propafenone and its metabolite have been shown to cross the placenta.
Adverse reactions such as fetal/neonatal arrhythmias have been associated with the use of other antiarrhythmic agents by pregnant women. Fetal/neonatal monitoring for signs and symptoms of arrhythmia is recommended during and after treatment of pregnant women with propafenone. Labor or Delivery: Risk of arrhythmias may increase during labor and delivery.
Patients treated with propafenone hydrochloride extended-release capsules should be monitored continuously for arrhythmias during labor and delivery [see Warnings and Precautions ( 5.1 )] . Data Propafenone has been shown to cause embryo-fetal mortality in rabbits and rats when given orally during organogenesis at maternally toxic doses of 150 mg/kg/day (rabbit: maternal mortality, decreased body weight gain and food consumption at approximately 3 times the MRHD on a mg/m 2 basis) and 600 mg/kg/day (rat: maternal decreased body weight gain and food consumption at approximately 6 times the MRHD on a mg/m 2 basis).
In addition, a maternally toxic dose of 600 mg/kg/day (approximately 6 times the MRHD on a mg/m 2 basis) also caused decreased fetal weights in rats. Increased placental weights and delayed ossification occurred in rabbits at a dose of 30 mg/kg/day (less than the MRHD on a mg/m 2 basis) in the absence of maternal toxicity. No adverse developmental outcomes in the absence of maternal toxicity were seen following oral doses of 15 mg/kg/day to rabbits or up to 270 mg/kg/day to rats administered during organogenesis (equivalent to 0.3 times or approximately 3 times the MRHD on a mg/m 2 basis, respectively).
In an oral study, female rats received propafenone up to 500 mg/kg/day from mid-gestation through weaning. At 90 mg/kg/day (equivalent to the MRHD on a mg/m 2 basis), there were no adverse developmental outcomes in the absence of maternal toxicity. However, doses ≥180 mg/kg/day (2 or more times the MRHD on a mg/m 2 basis) produced increases in maternal deaths and resulted in reductions in neonatal survival, body…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary In the absence of studies in pregnant women, available data from published case reports and several decades of postmarketing experience with use of propafenone hydrochloride extended-release capsules 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. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk: The incidence of VT is increased and may be more symptomatic during pregnancy.
Ventricular arrhythmias most often occur in pregnant women with underlying cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse. Breakthrough arrhythmias may also occur during pregnancy, as therapeutic treatment levels may be difficult to maintain due to the increased volume of distribution and increased drug metabolism inherent in the pregnant state. Fetal/Neonatal Adverse Reactions: Propafenone and its metabolite have been shown to cross the placenta.
Adverse reactions such as fetal/neonatal arrhythmias have been associated with the use of other antiarrhythmic agents by pregnant women. Fetal/neonatal monitoring for signs and symptoms of arrhythmia is recommended during and after treatment of pregnant women with propafenone. Labor or Delivery: Risk of arrhythmias may increase during labor and delivery.
Patients treated with propafenone hydrochloride extended-release capsules should be monitored continuously for arrhythmias during labor and delivery [see Warnings and Precautions ( 5.1 )] . Data Propafenone has been shown to cause embryo-fetal mortality in rabbits and rats when given orally during organogenesis at maternally toxic doses of 150 mg/kg/day (rabbit: maternal mortality, decreased body weight gain and food consumption at approximately 3 times the MRHD on a mg/m 2 basis) and 600 mg/kg/day (rat: maternal decreased body weight gain and food consumption at approximately 6 times the MRHD on a mg/m 2 basis).
In addition, a maternally toxic dose of 600 mg/kg/day (approximately 6 times the MRHD on a mg/m 2 basis) also caused decreased fetal weights in rats. Increased placental weights and delayed ossification occurred in rabbits at a dose of 30 mg/kg/day (less than the MRHD on a mg/m 2 basis) in the absence of maternal toxicity. No adverse developmental outcomes in the absence of maternal toxicity were seen following oral doses of 15 mg/kg/day to rabbits or up to 270 mg/kg/day to rats administered during organogenesis (equivalent to 0.3 times or approximately 3 times the MRHD on a mg/m 2 basis, respectively).
In an oral study, female rats received propafenone up to 500 mg/kg/day from mid-gestation through weaning. At 90 mg/kg/day (equivalent to the MRHD on a mg/m 2 basis), there were no adverse developmental outcomes in the absence of maternal toxicity. However, doses ≥180 mg/kg/day (2 or more times the MRHD on a mg/m 2 basis) produced increases in maternal deaths and resulted in reductions in neonatal survival, body weight gain, and delayed deve…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of propafenone in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the total number of subjects in Phase 3 clinical trials of propafenone hydrochloride extended-release 46% were 65 and older, while 16% were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals at higher doses cannot be ruled out. The effect of age on the pharmacokinetics and pharmacodynamics of propafenone has not been studied.
🆘 Overdosage ▾
10 OVERDOSAGE 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects and a direct stabilizing action on myocardial membranes. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and, to a lesser extent, myocardial fibers, propafenone reduces the fast inward current carried by sodium ions.
Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. Studies in anesthetized dogs and isolated organ preparations show that propafenone has beta-sympatholytic activity at about 1/50 the potency of propranolol.
Clinical studies employing isoproterenol challenge and exercise testing after single doses of propafenone indicate a beta-adrenergic blocking potency (per mg) about 1/40 that of propranolol in man. In clinical trials with the immediate-release formulation, resting heart rate decreases of about 8% were noted at the higher end of the therapeutic plasma concentration range. At very high concentrations in vitro , propafenone can inhibit the slow inward current carried by calcium, but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.
Moreover, propafenone inhibits a variety of cardiac potassium currents in in vitro studies (i.e., the transient outward, the delayed rectifier, and the inward rectifier current). Propafenone has local anesthetic activity approximately equal to procaine. Compared with propafenone, the main metabolite, 5-hydroxypropafenone, has similar sodium and calcium channel activity, but about 10 times less beta-blocking activity.
(N-depropylpropafenone has weaker sodium channel activity but equivalent affinity for beta-receptors.)
12.2Pharmacodynamics Cardiac Electrophysiology Electrophysiology trials in patients with ventricular tachycardia have shown that propafenone prolongs atrioventricular conduction while having little or no effect on sinus node function. Both atrioventricular nodal conduction time (AH interval) and His-Purkinje conduction time (HV interval) are prolonged. Propafenone has little or no effect on the atrial functional refractory period, but AV nodal functional and effective refractory periods are prolonged.
In patients with Wolff-Parkinson-White syndrome, Propafenone hydrochloride immediate-release tablets reduce conduction and increase the effective refractory period of the accessory pathway in both directions. Electrocardiograms: Propafenone prolongs the PR and QRS intervals. Prolongation of the QRS interval makes it difficult to interpret the effect of propafenone on the QT interval.
Table 1. Mean Change ± SD in 12-Lead Electrocardiogram Results (RAFT) Propafenone Hydrochloride Extended-release Capsules Twice-Daily Dosing Placebo 225 mg 325 mg 425 mg n = 126 n = 135 n = 136 n = 126 PR (ms) 9 ± 22 12 ± 23 21 ± 24 1 ± 16 QRS (ms) 4 ± 14 6 ± 15 6 ± 15 -2 ± 12 Heart rate 5 ± 24 7 ± 23 2 ± 22 8 ± 27 QTc a (ms) 2 ± 30 5 ± 36 6 ± 37 5 ± 35 a Calculated using Bazett's correction factor. In RAFT [see Clinical Studies (14)] , the distribution of the maximum changes in QTc compared with baseline over the trial in each patient was similar in the groups receiving propafenone hydrochloride extended-release capsules 225 mg twice daily, 325 mg twice daily, and 425 mg twice daily, and placebo.
Similar results were seen in the ERAFT trial. Table 2. Number of Patients According to the Range of Maximum QTc Change Compared with Baseline over the Trial in Each Dose Group (RAFT Trial).
Propafenone Hydrochloride Extended-release Capsules Placebo N = 100 n (%) Range Maximum QTc Change 225 mg Twice Daily N = 119 n (%) 325 mg Twice Daily N = 129 n (%) 425 mg Twice Daily N = 123 n (%) >20% 1 (1) 6 (5) 3 (2) 5 (4) 10 to 20% 19 (16) 28 (22) 32 (26) 24 (20) 0 ≤10% 99 (83) 95 (74) 88 (72) 91 (76) Hemodynamics Tria…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects and a direct stabilizing action on myocardial membranes. The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and, to a lesser extent, myocardial fibers, propafenone reduces the fast inward current carried by sodium ions.
Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. Studies in anesthetized dogs and isolated organ preparations show that propafenone has beta-sympatholytic activity at about 1/50 the potency of propranolol.
Clinical studies employing isoproterenol challenge and exercise testing after single doses of propafenone indicate a beta-adrenergic blocking potency (per mg) about 1/40 that of propranolol in man. In clinical trials with the immediate-release formulation, resting heart rate decreases of about 8% were noted at the higher end of the therapeutic plasma concentration range. At very high concentrations in vitro , propafenone can inhibit the slow inward current carried by calcium, but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.
Moreover, propafenone inhibits a variety of cardiac potassium currents in in vitro studies (i.e., the transient outward, the delayed rectifier, and the inward rectifier current). Propafenone has local anesthetic activity approximately equal to procaine. Compared with propafenone, the main metabolite, 5-hydroxypropafenone, has similar sodium and calcium channel activity, but about 10 times less beta-blocking activity.
(N-depropylpropafenone has weaker sodium channel activity but equivalent affinity for beta-receptors.)
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Propafenone Hydrochloride Extended-release Capsules, USP are supplied as hard gelatin capsules containing 225 mg, 325 mg or 425 mg of propafenone hydrochloride, USP. The 225 mg capsule has a white to off-white minitablets filled in the size "1" empty hard gelatin capsules having white opaque colored cap and white opaque colored body imprinted with '522' in black ink. They are available as follow: NDC 68382-522-14 in bottles of 60 capsules with child-resistance closure NDC 68382-522-05 in bottles of 500 capsules The 325 mg capsule has a white to off-white minitablets filled in the size "0" empty hard gelatin capsules having pink opaque colored cap and white opaque colored body imprinted with '523' in black ink.
They are available as follow: NDC 68382-523-14 in bottles of 60 capsules with child-resistance closure NDC 68382-523-05 in bottles of 500 capsules The 425 mg capsule has a white to off-white minitablets filled in the size "0el" empty hard gelatin capsules having red opaque colored cap and white opaque colored body imprinted with '524' in black ink. They are available as follow: NDC 68382-524-14 in bottles of 60 capsules with child-resistance closure NDC 68382-524-05 in bottles of 500 capsules Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature] .
Dispense in a tight container. Advise the patient to read the FDA-approved patient labeling (Patient Information).
📋 Description ▾
11 DESCRIPTION Propafenone hydrochloride, USP is an antiarrhythmic drug supplied in extended-release capsules of 225 mg, 325 mg, and 425 mg for oral administration. Chemically, propafenone hydrochloride, USP is 2'-[2-hydroxy-3-(propylamino)-propoxy]-3- phenylpropiophenone hydrochloride, with a molecular weight of 377.9. The molecular formula is C 21 H 27 NO 3 •HCl.
Propafenone hydrochloride, USP has some structural similarities to beta-blocking agents. The structural formula of propafenone hydrochloride, USP is given below: Propafenone hydrochloride, USP occurs as white powder. It is soluble in hot water and methanol and slightly soluble in chloroform.
Propafenone hydrochloride extended-release capsules, USP are filled with white to off-white minitablets containing propafenone hydrochloride, USP and the following inactive ingredients: colloidal silicon dioxide, hypromellose, magnesium stearate and silicon dioxide. In addition, each capsule contains gelatin, sodium lauryl sulphate and titanium dioxide. The 325 mg capsules also contain FD&C Blue 1 and FD & C Red 40.
The 425 mg capsules also contain FD & C Red 3, FD & C Red 40 and FD & C Yellow 6. The capsule is printed with black pharmaceutical ink which contains black iron oxide, potassium hydroxide and shellac. FDA approved dissolution method and acceptance criterion differ from the USP dissolution specification.
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💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Instruct patients to notify their healthcare providers of any change in over-the-counter, prescription, and supplement use. Instruct patients to report symptoms that may be associated with altered electrolyte balance, such as excessive or prolonged diarrhea, sweating, vomiting, or loss of appetite or thirst. Instruct patients not to double the next dose if a dose is missed.
The next dose should be taken at the usual time. Manufactured by: Zydus Lifesciences Ltd., Ahmedabad, India Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 Rev.: 11/22