United States - English - NLM (National Library of Medicine)

zydus lifesciences limited - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol tablets 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) and clinical studies (14.1) ]. carvedilol tablets 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 tablets are indicated for the management of essential hypertension [see  clinical studies (14.3, 14.4)] . it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see drug interactions (7.2)]. carvedilol tablets are contraindicated in the following conditions: - bronchial asthma or related bronchospastic conditions. d

United States - English - NLM (National Library of Medicine)

northwind pharmaceuticals, llc - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 6.25 mg - carvedilol tablets 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) and clinical studies ( 14.1) ]. carvedilol tablets 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 tablets are indicated for the management of essential hypertension [ see   clinical studies ( 14.3, 14.4)] . it can be used alone or in combination with other antihyper

United States - English - NLM (National Library of Medicine)

ncs healthcare of ky, inc dba vangard labs - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol is 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 ≤ 40% (with or without symptomatic heart failure) [ see clinical studies(14.1) ] . carvedilol is indicated for the management of essential hypertension [ see clinical studies (14.2, 14.3)]. it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see  drug interactions (7.2) ]. carvedilol is contraindicated in the following conditions: - bronchial asthma or related bronchospastic conditions. deaths from status asthmaticus have been reported following single doses of carvedilol - second- or third-degree av block - sick sinus syndrome - severe bradycardia (unless a permanent pacemaker is in place) - patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. such patients should first be weaned fro

United States - English - NLM (National Library of Medicine)

preferred pharmaceuticals,inc. - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 6.25 mg - carvedilol tablets 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 tablets 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 tablets are indicated for the management of essential hypertension [see  clinical studies (14.3, 14.4)] . it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see drug interactions (7.2)]. carvedilol tablets are contraindicated in the following conditions: risk summary available data regarding use of carvedilol 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 and any potential adverse effects on the breastfed infant from carvedilol or from the underlying maternal condition. effectiveness of carvedilol tablets 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 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%). of the 765 subjects with heart failure randomized to carvedilol in us 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 tablets 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 us clinical trials of efficacy or safety who were treated with carvedilol tablets, 21% (436) were aged 65 years or older. of 3,722 subjects receiving carvedilol tablets 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 figure 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.

United States - English - NLM (National Library of Medicine)

cardinal health 107, llc - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol tablets 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 tablets 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 tablets are indicated for the management of essential hypertension [see clinical studies (14.3, 14.4 )]. it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see  drug interactions (7.2) ]. carvedilol is contraindicated in the following conditions: risk summary available data regarding use of carvedilol 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 and any potential adverse effects on the breastfed infant from carvedilol 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 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%). 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 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.

United States - English - NLM (National Library of Medicine)

mylan pharmaceuticals inc. - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol tablets 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 tablets 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 tablets are indicated for the management of essential hypertension [see clinical studies (14.3, 14.4)] . it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see drug interactions (7.2)] . carvedilol tablets are contraindicated in the following conditions: available data regarding use of carvedilol tablets 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. 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. 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. 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. 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 tablets and any potential adverse effects on the breastfed infant from carvedilol tablets or from the underlying maternal condition. effectiveness of carvedilol tablets 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 carvedilol tablets and at twice the rate of placebo-treated subjects included chest pain (17% versus 6%), dizziness (13% versus 2%), and dyspnea (11% versus 0%). of the 765 subjects with heart failure randomized to carvedilol tablets 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 tablets 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 tablets in heart failure trials worldwide, 42% were aged 65 years or older. of the 975 subjects with myocardial infarction randomized to carvedilol tablets 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 tablets, 21% (436) were aged 65 years or older. of 3,722 subjects receiving carvedilol tablets 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.

United States - English - NLM (National Library of Medicine)

bluepoint laboratories - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol tablets 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 tablets 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 tablets are indicated for the management of essential hypertension [see clinical studies ( 14.3), ( 14.4) ) ]. it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see drug interactions(7.2)]. carvedilol tablets are contraindicated in the following conditions: - bronchial asthma or related bronchospastic conditions. deaths from status asthmaticus have been reported following single doses of carvedilol tablets. - second- or third-degree av block. - sick sinus syndrome. - severe bradycardia (unless a permanent pacemaker is in place). - patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. such patients should first be weaned from intravenous therapy before initiating carvedilol tablets. - patients with severe hepatic impairment. - patients with a history of a serious hypersensitivity reaction (e.g., stevens-johnson syndrome, anaphylactic reaction, angioedema) to any component of this medication or other medications containing carvedilol. risk summary available data regarding use of carvedilol 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 m 2 ) 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 m 2 ). 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 m 2 ), 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 m 2 ); in rabbits, it was 15 mg per kg per day (5 times the mrhd as mg per m 2 . 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 200mg per kg per day (approximately 32 times the mrhd as mg per m 2 ), 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 m 2 ) in the absence of maternal toxicity. the no-effect level was 12 mg per kg per day (2 times the mrhd as mg per m 2 ). 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 and any potential adverse effects on the breastfed infant from carvedilol or from the underlying maternal condition. effectiveness of carvedilol tablets 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 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%). of the 765 subjects with heart failure randomized to carvedilol in us 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 tablets 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 us clinical trials of efficacy or safety who were treated with carvedilol tablets, 21% (436) were aged 65 years or older. of 3,722 subjects receiving carvedilol tablets 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.

United States - English - NLM (National Library of Medicine)

nucare pharmaceuticals, inc. - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol tablets 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) and clinical studies (14.1) ]. carvedilol tablets 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 tablets are indicated for the management of essential hypertension [ see   clinical studies ( 14.3, 14.4)] . it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [ see drug interactions ( 7.2)] . carvedilol tablets are contraindicated in the following conditions: - bronchial asthma or related bronchospastic conditions. deaths from status asthmaticus have been reported following single doses of carvedilol tablets. - second- or third-degree av block. - sick sinus syndrome. - severe bradycardia (unless a permanent pacemaker is in place). - patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. such patients should first be weaned from intravenous therapy before initiating carvedilol tablets. - patients with severe hepatic impairment. - patients with a history of a serious hypersensitivity reaction (e.g., stevens-johnson syndrome, anaphylactic reaction, angioedema) to any component of this medication or other medications containing carvedilol. pregnancy category c. studies performed in pregnant rats and rabbits given carvedilol revealed increased post-implantation loss in rats at doses of 300 mg per kg per day (50 times the maximum recommended human dose [mrhd] as mg per m 2 ) and in rabbits at doses of 75 mg per kg per day (25 times the mrhd as mg per m 2 ). in the rats, there was also a decrease in fetal body weight at the maternally toxic dose of 300 mg per kg per day (50 times the mrhd as mg per m 2 ), which was accompanied by an elevation in the frequency of fetuses with delayed skeletal development (missing or stunted 13th rib). in rats the no-observed-effect level for developmental toxicity was 60 mg per kg per day (10 times the mrhd as mg per m 2 ); in rabbits it was 15 mg per kg per day (5 times the mrhd as mg per m 2 ). there are no adequate and well-controlled studies in pregnant women. carvedilol tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. it is not known whether this drug is excreted in human milk. studies in rats have shown that carvedilol and/or its metabolites (as well as other β-blockers) cross the placental barrier and are excreted in breast milk. there was increased mortality at one week post-partum in neonates from rats treated with 60 mg per kg per day (10 times the mrhd as mg per m 2 ) and above during the last trimester through day 22 of lactation. because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from β-blockers, especially bradycardia, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. the effects of other α- and β-blocking agents have included perinatal and neonatal distress. effectiveness of carvedilol tablets 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 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%). of the 765 subjects with heart failure randomized to carvedilol in us 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 myocardial infarction subjects randomized to carvedilol tablets 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 us clinical trials of efficacy or safety who were treated with carvedilol tablets, 21% (436) were aged 65 years or older. of 3,722 subjects receiving carvedilol tablets 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 figure 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.

United States - English - NLM (National Library of Medicine)

bayshore pharmaceuticals llc - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol tablets is 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 clinical studies (14.1)]. carvedilol tablet is 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 tablet is indicated for the management of essential hypertension [see clinical studies (14.3, 14.4) ]. it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see drug interactions (7.2) ]. carvedilol tablet is contraindicated in the following conditions: - bronchial asthma or related bronchospastic conditions. deaths from status asthmaticus have been reported following single doses of carvedilol tablet. - second- or third-degree av block - sick sinus syndrome - severe bradycardia (unless a permanent pacemaker is in place) - patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. such patients should first be weaned from intravenous therapy before initiating carvedilol tablet. - patients with severe hepatic impairment - patients with a history of a serious hypersensitivity reaction (e.g., stevens-johnson syndrome, anaphylactic reaction, angioedema) to any component of this medication or other medications containing carvedilol. risk summary available data regarding use of carvedilol 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 m’) 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 and any potential adverse effects on the breastfed infant from carvedilol or from the underlying maternal condition. effectiveness of carvedilol tablets in patients younger than 18 years of age has not been established. in a double-blind trial, 161 children (mean age 6 years, range 2 months to 17 years; 45% less than 2 years old) with chronic heart failure [nyha class ii to 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 two dose levels of carvedilol tablet. these dose levels produced placebo-corrected heart rate reduction of 4 to 6 heartbeats 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 patients treated with carvedilol tablet and at twice the rate of placebo-treated patients included chest pain (17% versus 6%), dizziness (13% versus 2%), and dyspnea (11% versus 0%). of the 765 subjects with heart failure randomized to carvedilol tablets in us clinical trials, 31% (235) were 65 years of age or older, and 7.3% (56) were 75 years of age or older. of the 1,156 subjects randomized to carvedilol tablets in a long-term, placebo-controlled trial in severe heart failure, 47% (547) were 65 years of age or older, and 15% (174) were 75 years of age or older. of 3,025 subjects receiving carvedilol tablets in heart failure trials worldwide, 42% were 65 years of age or older. of the 975 myocardial infarction patients randomized to carvedilol tablet in the capricorn trial, 48% (468) were 65 years of age or older, and 11% (111) were 75 years of age or older. of the 2,065 hypertensive patients in u.s. clinical trials of efficacy or safety who were treated with carvedilol tablet, 21% (436) were 65 years of age or older. of 3,722 patients receiving carvedilol tablet in hypertension clinical trials conducted worldwide, 24% were 65 years of age or older. with the exception of dizziness in hypertensive patients (incidence 8.8% in the elderly versus 6% in younger patients), no overall differences in the safety or effectiveness (see figure 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.

United States - English - NLM (National Library of Medicine)

state of florida doh central pharmacy - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - carvedilol tablets, usp 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 ≤40% (with or without symptomatic heart failure) [see clinical studies (14.2)] . carvedilol tablets, usp are indicated for the management of essential hypertension [see clinical studies (14.3, 14.4)] . it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see drug interactions (7.2)]. carvedilol tablets are contraindicated in the following conditions: - bronchial asthma or related bronchospastic conditions. deaths from status asthmaticus have been reported following single doses of carvedilol tablets. - second- or third-degree av block - sick sinus syndrome - severe bradycardia (unless a permanent pacemaker is in place) - patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy.