PROPAFENONE HYDROCHLORIDE capsule, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PROPAFENONE HYDROCHLORIDE (UNII: 33XCH0HOCD) (PROPAFENONE - UNII:68IQX3T69U)

Available from:

Actavis Pharma, Inc.

INN (International Name):

PROPAFENONE HYDROCHLORIDE

Composition:

PROPAFENONE HYDROCHLORIDE 225 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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 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 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/m2 basis) and 600 mg/kg/day (rat: maternal decreased body weight gain and food consumption at approximately 6 times the MRHD on a mg/m2 basis). In addition, a maternally toxic dose of 600 mg/kg/day (approximately 6 times the MRHD on a mg/m2 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/m2 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/m2 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/m2 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/m2 basis) produced increases in maternal deaths and resulted in reductions in neonatal survival, body weight gain, and delayed development in the presence of maternal toxicity. 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 mother’s clinical need for propafenone and any potential adverse effects on the breastfed infant from propafenone or from the underlying maternal condition. Infertility Males: Based on human and animal studies, propafenone hydrochloride 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)]. The safety and effectiveness of propafenone in pediatric patients have not been established. Of the total number of subjects in Phase 3 clinical trials of propafenone hydrochloride 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.

Product summary:

Propafenone Hydrochloride Extended-Release Capsules are supplied as opaque white capsules containing either 225 mg, 325 mg, or 425 mg of propafenone HCl. The 225 mg capsule is printed with “WPI” on cap and “2285” on body in black ink. The 325 mg capsule is printed with “WPI” on cap and “2286” on body in black ink. The 425 mg capsule is printed with “WPI” on cap and “2287” on body in black ink. The capsules are filled with white circular biconvex minitablets plain on both sides. Storage: Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].  Dispense in a tight container.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

PROPAFENONE HYDROCHLORIDE- PROPAFENONE HYDROCHLORIDE CAPSULE, EXTENDED
RELEASE
ACTAVIS PHARMA, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PROPAFENONE HYDROCHLORIDE
EXTENDED-RELEASE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR PROPAFENONE
HYDROCHLORIDE EXTENDED-RELEASE CAPSULES.
PROPAFENONE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 1989
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
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
Initiate therapy with 225 mg given