Propafenone hydrochloride capsule, extended release

8 use in specific populations

8.1 pregnancy

Risk Summary

In the absence of studies in pregnant women, available data from published case reports and several decades of

post-marketing 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 2basis) and 600 mg/kg/day (rat: maternal decreased body weight gain and food consumption at approximately 6 times the MRHD on a mg/m 2basis). In addition, a maternally toxic dose of 600 mg/kg/day (approximately 6 times the MRHD on a mg/m 2basis) 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 2basis) 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 2basis, 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 2basis), 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 2basis) produced increases in maternal deaths and resulted in reductions in neonatal survival, body weight gain, and delayed development in the presence of maternal toxicity.

8.2 lactation

Risk Summary

Propafenone and its active metabolite, 5-OH-propafenone, are present in human milk ,but the levels are likely to be low. There are no data on the effects of propafenone on the breastfed infant or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for propafenone and any potential adverse effects on the breastfed infant from propafenone or from the underlying maternal condition.

8.3 females and males of reproductive potential

Infertility

Males:Based on human and animal studies, propafenone hydrochloride extended-release capsules may transiently impair spermatogenesis in males. Evaluation of the effects on spermatogenesis was performed in 11 healthy males given oral propafenone 300 mg b.i.d. for 4 days, which was then increased to 300 mg t.i.d. for an additional 4 days. Study findings included a 28% reduction in semen sample volume on Treatment Day 8 and a 27% reduction in sperm count 64 days after treatment (both values remained within the laboratories normal reference range). These effects were not seen in follow-up visits up to 120 days after treatment. Reversible decreases in spermatogenesis have been demonstrated in monkeys, dogs, and rabbits after lethal or near-lethal intravenous doses of propafenone [see Nonclinical Toxicology (13.1)].

8.4 pediatric use

The safety and effectiveness of propafenone in pediatric patients have not been established.

8.5 geriatric 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.

Patient information

Propafenone Hydrochloride (proe pa fee none hye droe klor ide)

Extended-release Capsules

What are propafenone hydrochloride extended-release capsules?

Propafenone hydrochloride extended-release capsules are a prescription medicine that is used:

  • in certain people who have a heart rhythm disorder called atrial fibrillation (AF)
  • to increase the amount of time between having symptoms of AF

It is not known if propafenone hydrochloride extended-release capsules are safe and effective in children.

Who should not take propafenone hydrochloride extended-release capsules?

Do not take propafenone hydrochloride extended -release capsules if you have:

  • heart failure (weak heart)
  • had a recent heart attack
  • have a heart condition called Brugada Syndrome
  • a heart rate that is too slow, and you do not have a pacemaker
  • very low blood pressure
  • certain breathing problems that make you short of breath or wheeze
  • certain abnormal body salt (electrolyte) levels in your blood

Talk to your doctor before taking propafenone hydrochloride extended-release capsules if you think you have any of the conditions listed above.

What should I tell my doctor before taking propafenone hydrochloride extended-release capsules?

Before you take propafenone hydrochloride extended-release capsules tell your doctor if you:

  • have liver or kidney problems
  • have breathing problems
  • have symptoms including diarrhea, sweating, vomiting, or loss of appetite or thirst that are severe. These symptoms may be a sign of abnormal electrolyte levels in your blood.
  • have myasthenia gravis
  • have lupus erythematosus
  • have been told you have or had an abnormal blood test called Antinuclear Antibody Test or ANA Test
  • are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed. Propafenone hydrochloride can pass into your milk. You and your doctor
  • should discuss the best way to feed your baby during this time
  • have any other medical conditions

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Propafenone hydrochloride extended-release capsules and certain other medicines can affect each other and cause serious side effects. Propafenone hydrochloride extended-release capsules may affect the way other medicines work, and other medicines may affect how propafenone hydrochloride extended-release capsules work.

Especially tell your doctor if you take:

  • amiodarone or other medicines for your abnormal heart beats
  • an antidepressant medicine
  • a medicine to treat anxiety
  • ritonavir (for example, KALETRA ®, NORVIR ®) or saquinavir (for example, INVIRASE ®)
  • an antibiotic medicine
  • ketoconazole (for example, NIZORAL ®)
  • digoxin (LANOXIN ®)
  • warfarin sodium (for example, COUMADIN ®, JANTOVEN ®)

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take propafenone hydrochloride extended-release capsules?

  • Take propafenone hydrochloride extended-release capsules exactly as prescribed. Your doctor will tell you how many capsules to take and how often to take them.
  • To help reduce the chance of certain side effects, your doctor may start you with a low dose of propafenone hydrochloride extended-release capsules and then slowly increase the dose.
  • Do not open or crush the capsule.
  • You may take propafenone hydrochloride extended-release capsules with or without food.
  • You should not drink grapefruit juice during treatment with propafenone hydrochloride extended-release capsules
  • If you miss a dose of propafenone hydrochloride extended-release capsules take your next dose at the usual time. Do not take 2 doses at the same time.
  • If you take too much propafenone hydrochloride extended-release capsules call your doctor or go to the nearest hospital emergency room right away.
  • Call your doctor if your heart problems get worse.

What are possible side effects of propafenone hydrochloride extended-release capsules?
Propafenone hydrochloride extended-release capsules can cause serious side effects including:

  • New or worsened abnormal heart beats, that can cause sudden death or be life-threatening. Your doctor may do an electrocardiogram (ECG orEKG) before and during treatment to check your heart for these problems.
  • New or worsened heart failure. Tell your doctor about any changes in your heart symptoms, including:
    • oany new or increased swelling in your arms or legs
    • otrouble breathing
    • osudden weight gain
  • Effects on pacemaker function. Propafenone hydrochloride extended-release capsules may affect how an implanted pacemaker or defibrillator works. Your doctor should check how your pacemaker or defibrillator is working during and after treatment with propafenone hydrochloride extended-release capsules. They may need to be re-programmed.
  • Very low white blood cell levels in your blood (agranulocytosis). Your bone marrow may not produce enough of a certain type of white blood cells called neutrophils. If this happens, you are more likely to get infections. Tell your doctor right away if you have any of these symptoms, especially during the first 3 months of treatment:
    • ofever
    • osore throat
    • ochills
  • Worsening of myasthenia gravis in people who already have this condition. Tell your doctor about any change in your symptoms.
  • Propafenone hydrochloride extended-release capsules may cause lower sperm counts in men. This could affect the ability to father a child. Talk to your doctor if this is a concern for you.

Common side effects of propafenone hydrochloride extended-release capsules include:

  • dizziness
  • fast or irregular heart beats
  • chest pain
  • trouble breathing
  • taste changes
  • nausea
  • tiredness
  • feeling anxious
  • constipation
  • upper respiratory infection or flu
  • swelling

Tell your doctor if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of propafenone hydrochloride extended-release capsules. For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store propafenone hydrochloride extended-release capsules?

  • Store propafenone hydrochloride extended-release capsules at room temperature between 68F to 77F (20C to 25C).
  • Keep the bottle tightly closed.

Keep propafenone hydrochloride extended-release capsules and all medicines out of the reach of children.

General information about propafenone hydrochloride extended-release capsules
Medicines are sometimes prescribed for conditions other than those described in patient information leaflets. Do not use propafenone hydrochloride extended-release capsules for a condition for which it was not prescribed by your doctor. Do not give propafenone hydrochloride extended-release capsules to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about propafenone hydrochloride extended-release capsules. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about propafenone hydrochloride extended-release capsules that is written for healthcare professionals. For more information about propafenone hydrochloride extended-release capsules call 1-800-206-7821.

What are the ingredients in propafenone hydrochloride extended-release capsules?
Active Ingredient: Propafenone hydrochloride

Inactive Ingredients: black iron oxide, gelatin, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, potassium hydroxide, shellac, sodium lauryl sulfate and titanium dioxide.

Brands listed are trademarks of their respective owners and are not trademarks of Glenmark Pharmaceuticals Inc., USA. The makers of these brands are not affiliated with and do not endorse Glenmark Pharmaceuticals Inc., USA or its products.

Manufactured for:
Northstar Rx LLC
Memphis, TN 38141.

Manufactured by:
Glenmark Pharmaceuticals Ltd.
Plot No. 2, Phase-2, Pharma Zone SEZ, Pithampur,
Dist-Dhar, Madhya Pradesh 454775 India

April 2019

Ingredients and appearance - Product information

Propafenone hydrochloride capsule, extended release- Propafenone hydrochloride

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 16714-825
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Propafenone hydrochloride ( UNII: 33XCH0HOCD)( Propafenone - UNII: 68IQX3T69U ) 225 mgin 1

Inactive Ingredients

Ingredient Name Code
Lactose monohydrate ( UNII: EWQ57Q8I5X)
Microcrystalline cellulose ( UNII: OP1R32D61U)
Hypromellose, unspecified ( UNII: 3NXW29V3WO)
Magnesium stearate ( UNII: 70097M6I30)
Titanium dioxide ( UNII: 15FIX9V2JP)
Gelatin, unspecified ( UNII: 2G86QN327L)
Sodium lauryl sulfate ( UNII: 368GB5141J)
Shellac ( UNII: 46N107B71O)
Ferrosoferric oxide ( UNII: XM0M87F357)
Potassium hydroxide ( UNII: WZH3C48M4T)

Product Characteristics

Color WHITE (opaque white body) Size 22 mm
Shape CAPSULE (hard gelatin) Score 1
Imprint Code 408;G

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA205268 USA

Propafenone hydrochloride capsule, extended release- Propafenone hydrochloride

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 16714-826
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Propafenone hydrochloride ( UNII: 33XCH0HOCD)( Propafenone - UNII: 68IQX3T69U ) 325 mgin 1

Inactive Ingredients

Ingredient Name Code
Lactose monohydrate ( UNII: EWQ57Q8I5X)
Microcrystalline cellulose ( UNII: OP1R32D61U)
Hypromellose, unspecified ( UNII: 3NXW29V3WO)
Magnesium stearate ( UNII: 70097M6I30)
Titanium dioxide ( UNII: 15FIX9V2JP)
Gelatin, unspecified ( UNII: 2G86QN327L)
Sodium lauryl sulfate ( UNII: 368GB5141J)
Shellac ( UNII: 46N107B71O)
Ferrosoferric oxide ( UNII: XM0M87F357)
Potassium hydroxide ( UNII: WZH3C48M4T)

Product Characteristics

Color WHITE (opaque white body) Size 23 mm
Shape CAPSULE (hard gelatin) Score 1
Imprint Code 409;G

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA205268 USA

Propafenone hydrochloride capsule, extended release- Propafenone hydrochloride

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 16714-827
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Propafenone hydrochloride ( UNII: 33XCH0HOCD)( Propafenone - UNII: 68IQX3T69U ) 425 mgin 1

Inactive Ingredients

Ingredient Name Code
Lactose monohydrate ( UNII: EWQ57Q8I5X)
Microcrystalline cellulose ( UNII: OP1R32D61U)
Hypromellose, unspecified ( UNII: 3NXW29V3WO)
Magnesium stearate ( UNII: 70097M6I30)
Titanium dioxide ( UNII: 15FIX9V2JP)
Gelatin, unspecified ( UNII: 2G86QN327L)
Sodium lauryl sulfate ( UNII: 368GB5141J)
Shellac ( UNII: 46N107B71O)
Ferrosoferric oxide ( UNII: XM0M87F357)
Potassium hydroxide ( UNII: WZH3C48M4T)

Product Characteristics

Color WHITE (opaque white body with black band) Size 23 mm
Shape CAPSULE (hard gelatin) Score 1
Imprint Code 410;G

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA205268 USA

Labeler - Northstar Rx LLC( 830546433)

Establishment

Name ID/FEI Business Operations
Northstar Rx LLC 830546433 ANALYSIS( 16714-825, 16714-826, 16714-827), MANUFACTURE( 16714-825, 16714-826, 16714-827)