RYTHMOL SR- propafenone hydrochloride capsule, extended release

Šalis: Jungtinės Valstijos

kalba: anglų

Šaltinis: NLM (National Library of Medicine)

Veiklioji medžiaga:

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

Prieinama:

GlaxoSmithKline LLC

INN (Tarptautinis Pavadinimas):

PROPAFENONE HYDROCHLORIDE

Sudėtis:

PROPAFENONE HYDROCHLORIDE 225 mg

Vartojimo būdas:

ORAL

Recepto tipas:

PRESCRIPTION DRUG

Terapinės indikacijos:

RYTHMOL SR is 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: RYTHMOL SR is contraindicated in the following circumstances: Risk Summary There are no studies of RYTHMOL in pregnant women. Available data from published case reports and several decades of postmarketing experience with use of RYTHMOL 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 RYTHMOL 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, RYTHMOL 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 RYTHMOL SR (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.

Produkto santrauka:

RYTHMOL SR (propafenone HCl) capsules are supplied as white, opaque, hard gelatin capsules containing either 225 mg, 325 mg, or 425 mg of propafenone HCl. The 225-mg strength is imprinted in red with GS EUG followed by 225. The 325-mg strength is imprinted in red with GS F1Y followed by 325, and also has a single red band around ¾ of the circumference of the body. The 425-mg strength is imprinted in red with GS UY2 followed by 425, and also has 3 red bands around ¾ of the circumference of the body. Capsule Strength 60-count bottle NDC 225 mg 0173-0823-18 325 mg 0173-0824-18 425 mg 0173-0826-18 Storage: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Dispense in a tight container.

Autorizacija statusas:

New Drug Application

Prekės savybės

RYTHMOL SR- PROPAFENONE HYDROCHLORIDE CAPSULE, EXTENDED RELEASE
GLAXOSMITHKLINE LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
RYTHMOL SR SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING INFORMATION FOR RYTHMOL SR.
RYTHMOL SR (PROPAFENONE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES), FOR
ORAL USE
INITIAL U.S. APPROVAL: 1989
WARNING: MORTALITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_
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INDICATIONS AND USAGE
RYTHMOL SR is 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:
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
Capsules: 225 mg, 325 mg, 425 mg. (3)
CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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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.
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 RYTHMOL
SR with drugs that increase the atrioventricular
nodal refractory period. (1)
The effect of propafenone on mortality has not been determined. (1)
Initiate therapy with 225 mg