CARVEDILOL PHOSPHATE capsule, extended release

Pays: États-Unis

Langue: anglais

Source: NLM (National Library of Medicine)

Ingrédients actifs:

CARVEDILOL PHOSPHATE (UNII: EQT531S367) (CARVEDILOL - UNII:0K47UL67F2)

Disponible depuis:

Bryant Ranch Prepack

Mode d'administration:

ORAL

Type d'ordonnance:

PRESCRIPTION DRUG

indications thérapeutiques:

Carvedilol Phosphate extended-release capsules are indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see Drug Interactions (7.4), Clinical Studies (14.1)] . Carvedilol Phosphate extended-release capsules are indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of less than or equal to 40% (with or without symptomatic heart failure) [see Clinical Studies (14.2)] . Carvedilol Phosphate extended-release capsules are indicated for the management of essential hypertension [see Clinical Studies (14.3, 14.4)] . They can be used alone or in combination with other antihypertensive agents, especially thiazide‑type diuretics [see Drug Interactions (7.2)] . Carvedilol Phosphate extended-release capsules are contraindicated in the following conditions: Risk Summary Available data regarding use of Carvedilol Phosphate extended-release capsules in pregnant women are insufficient to determine whether there are drug-associated risks of adverse developmental outcomes. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy. The use of beta blockers during the third trimester of pregnancy may increase the risk of hypotension, bradycardia, hypoglycemia, and respiratory depression in the neonate (see Clinical Considerations). In animal reproduction studies, there was no evidence of adverse developmental outcomes at clinically relevant doses (see Data) . Oral administration of carvedilol to pregnant rats during organogenesis resulted in post-implantation loss, decreased fetal body weight, and an increased frequency of delayed fetal skeletal development at maternally toxic doses that were 50 times the maximum recommended human dose (MRHD). In addition, oral administration of carvedilol to pregnant rabbits during organogenesis resulted in increased post-implantation loss at doses 25 times the MRHD (see Data) . The estimated background risk 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: Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal Adverse Reactions: Neonates of women with hypertension who are treated with beta-blockers during the third trimester of pregnancy may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Observe newborns for symptoms of hypotension, bradycardia, hypoglycemia, and respiratory depression and manage accordingly. Data Animal Data: Studies performed in rats and rabbits given carvedilol during fetal organogenesis revealed increased post‑implantation loss in rats at a maternally toxic dose of 300 mg per kg per day (50 times the MRHD as mg per m2 ) and in rabbits (in the absence of maternal toxicity) at doses of 75 mg per kg per day (25 times the MRHD as mg per m2 ). In the rats, there was also a decrease in fetal body weight at 300 mg per kg per day (50 times the MRHD as mg per m2 ) accompanied by an increased incidence of fetuses with delayed skeletal development. In rats, the no-effect level for embryo-fetal toxicity was 60 mg per kg per day (10 times the MRHD as mg per m2 ); in rabbits, it was 15 mg per kg per day (5 times the MRHD as mg per m2 ). In a pre- and post-natal development study in rats administered carvedilol from late gestation through lactation, increased embryo-lethality was observed at a maternally toxic dose of 200 mg per kg per day (approximately 32 times the MRHD as mg per m2 ), and pup mortality and delays in physical growth/development were observed at 60 mg per kg per day (10 times the MRHD as mg per m2 ) in the absence of maternal toxicity. The no-effect level was 12 mg per kg per day (2 times the MRHD as mg per m2 ). Carvedilol was present in fetal rat tissue. Risk Summary There are no data on the presence of carvedilol in human milk, the effects on the breastfed infant, or the effects on milk production. Carvedilol is present in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Carvedilol Phosphate extended-release capsules and any potential adverse effects on the breastfed infant from Carvedilol Phosphate extended-release capsules or from the underlying maternal condition. Effectiveness of carvedilol in patients younger than 18 years has not been established. In a double-blind trial, 161 children (mean age: 6 years; range: 2 months to 17 years; 45% younger than 2 years) with chronic heart failure [NYHA class II-IV, left ventricular ejection fraction less than 40% for children with a systemic left ventricle (LV), and moderate-severe ventricular dysfunction qualitatively by echo for those with a systemic ventricle that was not an LV] who were receiving standard background treatment were randomized to placebo or to 2 dose levels of carvedilol. These dose levels produced placebo-corrected heart rate reduction of 4 to 6 heart beats per minute, indicative of β-blockade activity. Exposure appeared to be lower in pediatric subjects than adults. After 8 months of follow-up, there was no significant effect of treatment on clinical outcomes. Adverse reactions in this trial that occurred in greater than 10% of subjects treated with immediate-release carvedilol and at twice the rate of placebo-treated subjects included chest pain (17% versus 6%), dizziness (13% versus 2%), and dyspnea (11% versus 0%). The initial clinical trials of Carvedilol Phosphate extended-release capsules in subjects with hypertension, heart failure, and left ventricular dysfunction following myocardial infarction did not include sufficient numbers of subjects aged 65 years or older to determine whether they respond differently from younger patients. A randomized trial (n = 405) comparing subjects with mild to severe heart failure switched to Carvedilol Phosphate extended-release capsules or maintained on immediate-release carvedilol tablets included 220 subjects who were aged 65 years or older. In this elderly subgroup, the combined incidence of dizziness, hypotension, or syncope was 24% (18/75) in subjects switched from the highest dose of immediate-release carvedilol tablets (25 mg twice daily) to the highest dose of Carvedilol Phosphate extended-release capsules (80 mg once daily) compared with 11% (4/36) in subjects maintained on immediate-release carvedilol tablets (25 mg twice daily). When switching from the higher doses of immediate-release carvedilol tablets to Carvedilol Phosphate extended-release capsules, a lower starting dose is recommended for elderly patients [see Dosage and Administration (2.5)] . The following information is available for trials with immediate-release carvedilol. Of the 765 subjects with heart failure randomized to carvedilol in U.S. clinical trials, 31% (235) were aged 65 years or older, and 7.3% (56) were aged 75 years or older. Of the 1,156 subjects randomized to carvedilol in a long‑term, placebo‑controlled trial in severe heart failure, 47% (547) were aged 65 years or older, and 15% (174) were aged 75 years or older. Of 3,025 subjects receiving carvedilol in heart failure trials worldwide, 42% were aged 65 years or older. Of the 975 subjects with myocardial infarction randomized to carvedilol in the CAPRICORN trial, 48% (468) were aged 65 years or older, and 11% (111) were aged 75 years or older. Of the 2,065 hypertensive subjects in U.S. clinical trials of efficacy or safety who were treated with carvedilol, 21% (436) were aged 65 years or older. Of 3,722 subjects receiving immediate-release carvedilol in hypertension clinical trials conducted worldwide, 24% were aged 65 years or older. With the exception of dizziness in hypertensive subjects (incidence 8.8% in the elderly versus 6% in younger subjects), no overall differences in the safety or effectiveness (see Figures 2 and 4) were observed between the older subjects and younger subjects in each of these populations. Similarly, other reported clinical experience has not identified differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Descriptif du produit:

The hard gelatin capsules are available in the following strengths: Store at 25°C (77°F); excursions 15° to 30°C (59° to 86°F). Dispense in a tight, light‑resistant container.

Statut de autorisation:

New Drug Application Authorized Generic

Résumé des caractéristiques du produit

CARVEDILOL PHOSPHATE- CARVEDILOL PHOSPHATE CAPSULE, EXTENDED RELEASE
BRYANT RANCH PREPACK
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CARVEDILOL PHOSPHATE
EXTENDED-RELEASE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
CARVEDILOL PHOSPHATE EXTENDED-RELEASE CAPSULES.
CARVEDILOL PHOSPHATE EXTENDED-RELEASE CAPSULES FOR ORAL USE
INITIAL U.S. APPROVAL: 1995
INDICATIONS AND USAGE
Carvedilol Phosphate extended-release capsules are an
alpha-/beta-adrenergic blocking agent indicated
for the treatment of:
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DOSAGE AND ADMINISTRATION
Take with food. Do not crush or chew capsules. Individualize dosage
and monitor during up-titration. (2)
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DOSAGE FORMS AND STRENGTHS
Capsules: 10 mg, 20 mg, 40 mg, 80 mg (3)
CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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ADVERSE REACTIONS
The safety profile of Carvedilol Phosphate extended-release was
similar to that observed for immediate-
mild to severe chronic heart failure. (1.1)
left ventricular dysfunction following myocardial infarction in
clinically stable patients. (1.2)
hypertension. (1.3)
Heart failure: Start at 10 mg once daily and increase to 20, 40, and
then 80 mg once daily over
intervals of at least 2 weeks. Maintain lower doses if higher doses
are not tolerated. (2.1)
Left ventricular dysfunction following myocardial infarction: Start at
20 mg once daily and increase to
40 mg then 80 mg once daily after intervals of 3 to 10 days. A lower
starting dose or slower titration
may be used. (2.2)
Hypertension: Start at 20 mg once daily and increase if needed for
blood pressure control to 40 mg
then 80 mg once daily over intervals of 1 to 2 weeks. (2.3)
Elderly patients (> 65 years of age): When switching from higher doses
of immediate-release
carvedilol tablets to Carvedilol Phosphate extended-release capsules,
a lower starting dose should be
considered to reduce the risk of hypotension and syncope. (2.5)
Bronchial asthma or rel