Spojené štáty - angličtina - NLM (National Library of Medicine)

winthrop u.s, a business of sanofi-aventis u.s. llc - irbesartan (unii: j0e2756z7n) (irbesartan - unii:j0e2756z7n) - irbesartan is indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular (cv) events, primarily strokes and myocardial infarction. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program's joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. irbesartan may be used alone or in combination with other antihypertensive agents. irbesartan is indicated for the treatment of diabetic nephropathy in patients with type 2 diabetes and hypertension, an elevated serum creatinine, and proteinuria (>300 mg/day). in this population, irbesartan reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end-stage renal disease (need for dialysis or renal transplantation) [see clinical studies (14.2)] . irbesartan is contraindicated in patients who are hypersensitive to any component of this product. do not coadminister aliskiren with irbesartan in patients with diabetes. risk summary irbesartan can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see clinical considerations]. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue irbesartan as soon as possible. all pregnancies have a background risk of birth defect, loss or other adverse outcomes regardless of drug exposure. 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 preeclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and postpartum 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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. in the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of pregnancy. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. if oligohydramnios is observed, consider alternative treatment. closely observe infants with histories of in utero exposure to irbesartan for hypotension, oliguria, and hyperkalemia and other symptoms of renal impairment. in neonates with a history of in utero exposure to irbesartan, if oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. data animal data irbesartan crosses the placenta in rats and rabbits. in female rats given irbesartan prior to mating through gestation and lactation at oral doses of 50, 180, or 650 mg/kg/day (1.6 to 21.1 times the maximum recommended human dose (mrhd) based on body surface area), fetuses examined on gestation day 20 showed increased incidences of hydroureter and renal pelvic cavitation and/or absence of renal papilla in all irbesartan-treated groups. subcutaneous edema also occurred in fetuses at maternal doses ≥180 mg/kg/day (5.8 times the mrhd). these anomalies occurred when female rats received irbesartan from prior to mating through day 20 of gestation but were not observed in pups postnatally in the same study, or when irbesartan was given to pregnant rats only during organogenesis (gestation day 6 through gestation day 15) at oral doses from 50 to 450 mg/kg/day (up to 14.6 times the mrhd). in addition, no adverse effects on kidney development were observed in pups from dams given irbesartan from gestation day 15 through lactation day 24 at doses of 50, 180, or 650 mg/kg/day (up to 21.1 times the mrhd). the observed effects are believed to be late gestational effects of the drug. pregnant rabbits given oral doses of irbesartan of 30 mg/kg/day (1.9 times the mrhd based on body surface area) experienced a high rate of maternal mortality and abortion. surviving females had a slight increase in early resorptions and a corresponding decrease in live fetuses. radioactivity was present in the rat and rabbit fetuses during late gestation following oral doses of radiolabeled irbesartan. there are no available data on the presence of irbesartan in human milk, effects on milk production, or the breastfed infant. irbesartan or some metabolite of irbesartan is secreted in the milk of lactating rats [see clinical pharmacology (12.3)] . because of the potential for adverse effects on the nursing infant, the use of irbesartan in breastfeeding women is not recommended. irbesartan, in a study at a dose of up to 4.5 mg/kg/day, once daily, did not appear to lower blood pressure effectively in pediatric patients ages 6 to 16 years. irbesartan has not been studied in pediatric patients less than 6 years old. of 4925 subjects receiving irbesartan in controlled clinical studies of hypertension, 911 (18.5%) were 65 years and over, while 150 (3.0%) were 75 years and over. no overall differences in effectiveness or safety were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. [see clinical pharmacology (12.3)and clinical studies (14.1).]

Spojené štáty - angličtina - NLM (National Library of Medicine)

remedyrepack inc. - olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - olmesartan medoxomil tablets are indicated for the treatment of hypertension in adults and children six years of age and older, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with olmesartan medoxomil. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. it may be used alone or in combination with other antihypertensive agents. do not co-administer aliskiren with olmesartan medoxomil tablets in patients with diabetes [see drug interactions (7.3)]. risk summary olmesartan medoxomil tablets can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. in animal reproduction studies, olmesartan medoxomil treatment during organogenesis resulted in increased embryofetal toxicity in rats at doses lower than maternally toxic doses. when pregnancy is detected, discontinue olmesartan medoxomil as soon as possible. consider alternative antihypertensive therapy during pregnancy. the estimated background risk of major birth defects and miscarriage for the indicated population is 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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. in patients taking olmesartan medoxomil during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to olmesartan medoxomil for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to olmesartan medoxomil, if oliguria or hypotension occurs, utilize measures to maintain adequate blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function. data animal data no teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose (mrhd) on a mg/m 2 basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the mrhd on a mg/m 2 basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the does). in rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricula, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥ 8 mg/kg/day. the no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the mrhd of 40 mg/day. risk summary there is no information regarding the presence of olmesartan in human milk, the effects on the breastfed infant, or the effects on milk production. olmesartan is secreted at low concentration in the milk of lactating rats (see data). because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. data presence of olmesartan in milk was observed after a single oral administration of 5 mg/kg [14c] olmesartan medoxomil to lactating rats. the antihypertensive effects of olmesartan medoxomil were evaluated in one randomized, double-blind clinical study in pediatric patients 1 to 16 years of age [see clinical studies (14.2)] . the pharmacokinetics of olmesartan medoxomil was evaluated in pediatric patients 1 to 16 years of age [see clinical pharmacology (12.3)] . olmesartan medoxomil was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. olmesartan medoxomil has not been shown to be effective for hypertension in children <6 years of age. use of olmesartan medoxomil in children <1 year of age is not recommended [see warnings and precautions (5.2)] . the renin-angiotensin-aldosterone system (raas) plays a critical role in kidney development. raas blockade has been shown to lead to abnormal kidney development in very young mice. administering drugs that act directly on the renin-angiotensin aldosterone system (raas) can alter normal renal development. of the total number of hypertensive patients receiving olmesartan medoxomil in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. no overall differences in effectiveness or safety were observed between elderly patients and younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)] . increases in auc 0- ∞ and c max were observed in patients with moderate hepatic impairment compared to those in matched controls, with an increase in auc of about 60%. no initial dosage adjustment is recommended for patients with moderate to marked hepatic dysfunction [see  clinical pharmacology (12.3)] . patients with renal insufficiency have elevated serum concentrations of olmesartan compared to subjects with normal renal function. after repeated dosing, the auc was approximately tripled in patients with severe renal impairment (creatinine clearance <20 ml/min). no initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 ml/min) [see dosage and administration (2.1), warnings and precautions (5.4)and clinical pharmacology (12.3)] . the antihypertensive effect of olmesartan medoxomil was smaller in black patients (usually a low-renin population), as has been seen with ace inhibitors, beta-blockers and other angiotensin receptor blockers.

Spojené štáty - angličtina - NLM (National Library of Medicine)

remedyrepack inc. - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288), benazepril hydrochloride (unii: n1sn99t69t) (benazeprilat - unii:jrm708l703) - amlodipine and benazepril hydrochloride capsules are indicated for the treatment of hypertension in patients not adequately controlled on monotherapy with either agent. - do not coadminister aliskiren with angiotensin receptor blockers (arbs), ace inhibitors, including amlodipine and benazepril hydrochloride in patients with diabetes. - amlodipine and benazepril hydrochloride is contraindicated in patients with a history of angioedema, with or without previous ace inhibitor treatment, or patients who are hypersensitive to benazepril, to any other ace inhibitor, to amlodipine, or to any of the excipients of amlodipine and benazepril hydrochloride capsules. - amlodipine and benazepril hydrochloride is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). do not administer amlodipine and benazepril hydrochloride capsules within 36 hours of switching to or from a neprilysin inhibitor, e.g., sacubitril/valsartan [see warnings and precautions ( 5.1)] . risk summary amlodipine and benazepril hydrochloride capsules can cause fetal harm when administered to a pregnant woman. use of drugs that act on the ras during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the ras from other antihypertensive agents. when pregnancy is detected, discontinue amlodipine and benazepril hydrochloride capsules as soon as possible. the estimated background risk of major birth defects and miscarriage for the indicated population is 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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. if oligohydramnios is observed, consider alternative drug treatment. closely observe neonates with histories of in utero exposure to amlodipine and benazepril hydrochloride for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to amlodipine and benazepril hydrochloride, if oliguria or hypotension occurs, support blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. data animal data benazepril and amlodipine: when rats received benazepril:amlodipine at doses ranging from 5:2.5 to 50:25 mg/kg/day, dystocia was observed at an increasing dose-related incidence at all doses tested. on a body surface area basis, the 2.5 mg/kg/day dose of amlodipine is twice the amlodipine dose delivered when the maximum recommended dose of amlodipine and benazepril hydrochloride capsules is given to a 60 kg patient. similarly, the 5 mg/kg/day dose of benazepril is approximately equivalent with the benazepril dose delivered when the maximum recommended dose of amlodipine and benazepril hydrochloride capsules is given to a 60 kg patient. no teratogenic effects were seen when benazepril and amlodipine were administered in combination to pregnant rats or rabbits. rats received doses of up to 50:25 mg (benazepril:amlodipine)/kg/day (12 times the mrhd on a body surface area basis, assuming a 60 kg patient). rabbits received doses of up to 1.5:0.75 mg/kg/day (equivalent to the maximum recommended dose of amlodipine and benazepril hydrochloride capsules given to a 60 kg patient). risk summary minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women treated with benazepril, so that a newborn child ingesting nothing but breast milk would receive less than 0.1% of the maternal doses of benazepril and benazeprilat. limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. no adverse effects of amlodipine on the breastfed infant have been observed. there is no available information on the effects of amlodipine or benazepril on milk production. safety and effectiveness in pediatric patients have not been established. in geriatric patients, exposure to amlodipine is increased, thus consider lower initial doses of amlodipine and benazepril hydrochloride [see clinical pharmacology ( 12.3)]. of the total number of patients who received amlodipine and benazepril hydrochloride in u.s. clinical studies of amlodipine and benazepril hydrochloride, over 19% were 65 years or older while about 2% were 75 years or older. overall differences in effectiveness or safety were not observed between these patients and younger patients. clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. exposure to amlodipine is increased in patients with hepatic insufficiency, thus consider using lower doses of amlodipine and benazepril hydrochloride capsules [see clinical pharmacology ( 12.3)] . in patients with severe renal impairment systemic exposure to benazepril is increased. the recommended dose of benazepril in this subgroup is 5 mg which is not an available strength with amlodipine and benazepril hydrochloride capsules. amlodipine and benazepril hydrochloride capsules are not recommended in patients with severe renal impairment. no dose adjustment of amlodipine and benazepril hydrochloride capsules is needed in patients with mild or moderate impairment of renal function [see dosage and administration ( 2.2), warnings and precautions ( 5.7) and clinical pharmacology ( 12.3)] .

Spojené štáty - angličtina - NLM (National Library of Medicine)

lifestar pharma llc - olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - olmesartan medoxomil is indicated for the treatment of hypertension in adults and children six years of age and older, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with olmesartan medoxomil tablets. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. it may be used alone or in combination with other antihypertensive agents. do not co-administer aliskiren with olmesartan medoxomil tablets in patients with diabetes [see drug interactions (7.3)]. risk summary olmesartan medoxomil tablets can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. in animal reproduction studies, olmesartan medoxomil tablets treatment during organogenesis resulted in increased embryofetal toxicity in rats at doses lower than maternally toxic doses. when pregnancy is detected, discontinue olmesartan medoxomil tablets as soon as possible. consider alternative antihypertensive therapy during pregnancy. the estimated background risk of major birth defects and miscarriage for the indicated population is 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%–4% and 15%–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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. in patients taking olmesartan medoxomil during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to olmesartan medoxomil for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to olmesartan medoxomil, if oliguria or hypotension occurs, utilize measures to maintain adequate blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function. data animal data no teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose (mrhd) on a mg/m 2 basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the mrhd on a mg/m 2 basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the does). in rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricula, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥ 8 mg/kg/day. the no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the mrhd of 40 mg/day. risk summary there is no information regarding the presence of olmesartan in human milk, the effects on the breastfed infant, or the effects on milk production. olmesartan is secreted at low concentration in the milk of lactating rats (see data) . because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. data presence of olmesartan in milk was observed after a single oral administration of 5 mg/kg [ 14 c] olmesartan medoxomil to lactating rats. the antihypertensive effects of olmesartan medoxomil tablets were evaluated in one randomized, double-blind clinical study in pediatric patients 1 to 16 years of age [see clinical studies (14.2)] . the pharmacokinetics of olmesartan medoxomil tablets were evaluated in pediatric patients 1 to 16 years of age [see clinical pharmacology (12.3)] . olmesartan medoxomil tablets was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. olmesartan medoxomil tablets have not been shown to be effective for hypertension in children <6 years of age. use of olmesartan medoxomil in children <1 year of age is not recommended [see warnings and precautions (5.2)]. the renin-angiotensin aldosterone system (raas) plays a critical role in kidney development. raas blockade has been shown to lead to abnormal kidney development in very young mice. administering drugs that act directly on the renin­ angiotensin aldosterone system (raas) can alter normal renal development. of the total number of hypertensive patients receiving olmesartan medoxomil tablets in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. no overall differences in effectiveness or safety were observed between elderly patients and younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)]. increases in auc 0-∞ and c max were observed in patients with moderate hepatic impairment compared to those in matched controls, with an increase in auc of about 60%. no initial dosage adjustment is recommended for patients with moderate to marked hepatic dysfunction [see clinical pharmacology (12.3)]. patients with renal insufficiency have elevated serum concentrations of olmesartan compared to subjects with normal renal function. after repeated dosing, the auc was approximately tripled in patients with severe renal impairment (creatinine clearance <20 ml/min). no initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 ml/min) [see dosage and administration (2.1) ,  warnings and precautions (5.4) and clinical pharmacology (12.3)]. the antihypertensive effect of olmesartan medoxomil tablets was smaller in black patients (usually a low-renin population), as has been seen with ace inhibitors, beta-blockers and other angiotensin receptor blockers.

Spojené štáty - angličtina - NLM (National Library of Medicine)

remedyrepack inc. - irbesartan (unii: j0e2756z7n) (irbesartan - unii:j0e2756z7n) - irbesartan tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular (cv) events, primarily strokes and myocardial infarction. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. irbesartan tablets may be used alone or in combination with other antihypertensive agents. irbesartan tablets are indicated for the treatment of diabetic nephropathy in patients with type 2 diabetes and hypertension, an elevated serum creatinine, and proteinuria (>300 mg/day). in this population, irbesartan reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end-stage renal disease (need for dialysis or renal transplantation) [see clinical studies ( 14.2)]. irbesartan tablets are contraindicated in patients who are hypersensitive to any component of this product. do not co-administrate aliskiren with irbesartan tablets in patients with diabetes. risk summary   irbesartan can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see clinical considerations]. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue irbesartan as soon as possible.  all pregnancies have a background risk of birth defect, loss or other adverse outcomes regardless of drug exposure. 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 preeclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and postpartum 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  oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. in the unusual case that there is no appropriate alternative to therapy with drugs affecting the reninangiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.  perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of pregnancy. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. if oligohydramnios is observed, consider alternative treatment. closely observe infants with histories of in utero exposure to irbesartan for hypotension, oliguria, and hyperkalemia and other symptoms of renal impairment. in neonates with a history of in utero exposure to irbesartan, if oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.  data  animal data  irbesartan crosses the placenta in rats and rabbits. in female rats given irbesartan prior to mating though gestation and lactation at oral doses of 50, 180, or 650 mg/kg/day (1.6 to 21.1 times the maximum recommended human dose (mrhd) based on body surface area), fetuses examined on gestation day 20 showed increased incidences of hydroureter and renal pelvic cavitation and/or absence of renal papilla in all irbesartan-treated groups. subcutaneous edema also occurred in fetuses at maternal doses ≥180 mg/kg/day (5.8 times the mrhd). these anomalies occurred when female rats received irbesartan from prior to mating through day 20 of gestation but were not observed in pups postnatally in the same study, or when irbesartan was given to pregnant rats only during organogenesis (gestation day 6 through gestation day 15) at oral doses from 50 to 450 mg/kg/day (up to 14.6 times the mrhd). in addition, no adverse effects on kidney development were observed in pups from dams given irbesartan from gestation day 15 through lactation day 24 at doses of 50, 180, or 650 mg/kg/day (up to 21.1 times the mrhd). the observed effects are believed to be late gestational effects of the drug. pregnant rabbits given oral doses of irbesartan of 30 mg/kg/day (1.9 times the mrhd based on body surface area) experienced a high rate of maternal mortality and abortion. surviving females had a slight increase in early resorptions and a corresponding decrease in live fetuses.  radioactivity was present in the rat and rabbit fetuses during late gestation following oral doses of radiolabeled irbesartan. there are no available data on the presence of irbesartan in human milk, effects on milk production, or the breastfed infant. irbesartan or some metabolite of irbesartan is secreted in the milk of lactating rats [see clinical pharmacology (12.3)] . because of the potential for adverse effects on the nursing infant, the use of irbesartan in breastfeeding women is not recommended.  irbesartan, in a study at a dose of up to 4.5 mg/kg/day, once daily, did not appear to lower blood pressure effectively in pediatric patients ages 6 to 16 years. irbesartan has not been studied in pediatric patients less than 6 years old. of 4925 subjects receiving irbesartan in controlled clinical studies of hypertension, 911 (18.5%) were 65 years and over, while 150 (3.0%) were 75 years and over. no overall differences in effectiveness or safety were observed between these subjects and younger  subjects, but greater sensitivity of some older individuals cannot be ruled out. [see clinical pharmacology ( 12.3) and clinical studies ( 14.1).]

Spojené štáty - angličtina - NLM (National Library of Medicine)

preferred pharmaceuticlas inc. - benazepril hydrochloride (unii: n1sn99t69t) (benazeprilat - unii:jrm708l703) - benazepril hydrochloride tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mm hg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. it may be used alone or in combination with thiazide diuretics. benazepril hydrochloride tablets are contraindicated in patients: benazepril hydrochloride tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). do not administer benazepril hydrochloride tablets within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see warnings and precautions (5.2)]. do not coadminister aliskiren with angiotensin receptor blockers, ace inhibitors; including benazepril hydrochloride tablets in patients with diabetes [see drug interactions (7.4)] . risk summary  benazepril can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue benazepril as soon as possible. the estimated background risk of major birth defects and miscarriage for the indicated population are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the general u.s. 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     oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. in the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of pregnancy. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to benazepril for hypotension, oliguria, and hyperkalemia. if oliguria or hypotension occur in neonates with a history of in utero exposure to benazepril, support blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.  minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women treated with benazepril. a newborn child ingesting entirely breast milk would receive less than 0.1% of the mg/kg maternal dose of benazepril and benazeprilat. the antihypertensive effects of benazepril have been evaluated in a double-blind study in pediatric patients 7 to 16 years of age [see clinical pharmacology (12.3)] . the pharmacokinetics of benazepril have been evaluated in pediatric patients 6 to 16 years of age [see clinical pharmacology (12.3)] . infants below the age of 1 year should not be given benazepril because of the risk of effects on kidney development. safety and effectiveness of benazepril have not been established in pediatric patients less than 6 years of age or in children with glomerular filtration rate < 30 ml/min/1.73m² [see dosage and administration (2.1) and clinical pharmacology 12.3)].   of the total number of patients who received benazepril in u.s. clinical studies of benazepril, 18% were 65 or older while 2% were 75 or older. no overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. benazepril and benazeprilat are substantially excreted by the kidney. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see dosage and administration (2.2)] . ace inhibitors, including benazepril, as monotherapy, have an effect on blood pressure that is less in black patients than in non-blacks. dose adjustment of benazepril is required in patients undergoing hemodialysis or whose creatinine clearance is ≤ 30 ml/min. no dose adjustment of benazepril is required in patients with creatinine clearance > 30 ml/min [see dosage and administration (2.2) and clinical pharmacology (12.3)] .

Spojené štáty - angličtina - NLM (National Library of Medicine)

remedyrepack inc. - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288), benazepril hydrochloride (unii: n1sn99t69t) (benazeprilat - unii:jrm708l703) - amlodipine and benazepril hydrochloride capsules are indicated for the treatment of hypertension in patients not adequately controlled on monotherapy with either agent. - do not coadminister aliskiren with angiotensin receptor blockers (arbs), ace inhibitors, including amlodipine and benazepril hydrochloride in patients with diabetes. - amlodipine and benazepril hydrochloride is contraindicated in patients with a history of angioedema, with or without previous ace inhibitor treatment, or patients who are hypersensitive to benazepril, to any other ace inhibitor, to amlodipine, or to any of the excipients of amlodipine and benazepril hydrochloride capsules. - amlodipine and benazepril hydrochloride is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). do not administer amlodipine and benazepril hydrochloride capsules within 36 hours of switching to or from a neprilysin inhibitor, e.g., sacubitril/valsartan [see warnings and precautions ( 5.1)] . risk summary amlodipine and benazepril hydrochloride capsules can cause fetal harm when administered to a pregnant woman. use of drugs that act on the ras during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the ras from other antihypertensive agents. when pregnancy is detected, discontinue amlodipine and benazepril hydrochloride capsules as soon as possible. the estimated background risk of major birth defects and miscarriage for the indicated population is 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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. if oligohydramnios is observed, consider alternative drug treatment. closely observe neonates with histories of in utero exposure to amlodipine and benazepril hydrochloride for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to amlodipine and benazepril hydrochloride, if oliguria or hypotension occurs, support blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. data animal data benazepril and amlodipine: when rats received benazepril:amlodipine at doses ranging from 5:2.5 to 50:25 mg/kg/day, dystocia was observed at an increasing dose-related incidence at all doses tested. on a body surface area basis, the 2.5 mg/kg/day dose of amlodipine is twice the amlodipine dose delivered when the maximum recommended dose of amlodipine and benazepril hydrochloride capsules is given to a 60 kg patient. similarly, the 5 mg/kg/day dose of benazepril is approximately equivalent with the benazepril dose delivered when the maximum recommended dose of amlodipine and benazepril hydrochloride capsules is given to a 60 kg patient. no teratogenic effects were seen when benazepril and amlodipine were administered in combination to pregnant rats or rabbits. rats received doses of up to 50:25 mg (benazepril:amlodipine)/kg/day (12 times the mrhd on a body surface area basis, assuming a 60 kg patient). rabbits received doses of up to 1.5:0.75 mg/kg/day (equivalent to the maximum recommended dose of amlodipine and benazepril hydrochloride capsules given to a 60 kg patient). risk summary minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women treated with benazepril, so that a newborn child ingesting nothing but breast milk would receive less than 0.1% of the maternal doses of benazepril and benazeprilat. limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. no adverse effects of amlodipine on the breastfed infant have been observed. there is no available information on the effects of amlodipine or benazepril on milk production. safety and effectiveness in pediatric patients have not been established. in geriatric patients, exposure to amlodipine is increased, thus consider lower initial doses of amlodipine and benazepril hydrochloride [see clinical pharmacology ( 12.3)]. of the total number of patients who received amlodipine and benazepril hydrochloride in u.s. clinical studies of amlodipine and benazepril hydrochloride, over 19% were 65 years or older while about 2% were 75 years or older. overall differences in effectiveness or safety were not observed between these patients and younger patients. clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. exposure to amlodipine is increased in patients with hepatic insufficiency, thus consider using lower doses of amlodipine and benazepril hydrochloride capsules [see clinical pharmacology ( 12.3)] . in patients with severe renal impairment systemic exposure to benazepril is increased. the recommended dose of benazepril in this subgroup is 5 mg which is not an available strength with amlodipine and benazepril hydrochloride capsules. amlodipine and benazepril hydrochloride capsules are not recommended in patients with severe renal impairment. no dose adjustment of amlodipine and benazepril hydrochloride capsules is needed in patients with mild or moderate impairment of renal function [see dosage and administration ( 2.2), warnings and precautions ( 5.7) and clinical pharmacology ( 12.3)] .

Spojené štáty - angličtina - NLM (National Library of Medicine)

bryant ranch prepack - olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - olmesartan medoxomil tablets are indicated for the treatment of hypertension in adults and children six years of age and older, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with olmesartan medoxomil. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. it may be used alone or in combination with other antihypertensive agents. do not co-administer aliskiren with olmesartan medoxomil in patients with diabetes [see drug interactions (7.3)]. risk summary olmesartan medoxomil can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. in animal reproduction studies, olmesartan medoxomil treatment during organogenesis resulted in increased embryofetal toxicity in rats at doses lower than maternally toxic doses. when pregnancy is detected, discontinue olmesartan medoxomil as soon as possible. consider alternative antihypertensive therapy during pregnancy. the estimated background risk of major birth defects and miscarriage for the indicated population is 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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. in patients taking olmesartan medoxomil tablets during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to olmesartan medoxomil for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to olmesartan medoximil, if oliguria or hypotension occurs, utilize measures to maintain adequate blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function. data animal data no teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose (mrhd) on a mg/m 2 basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the mrhd on a mg/m 2 basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the does). in rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricula, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥ 8 mg/kg/day. the no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the mrhd of 40 mg/day. risk summary there is no information regarding the presence of olmesartan in human milk, the effects on the breastfed infant, or the effects on milk production. olmesartan is secreted at low concentration in the milk of lactating rats (see data) . because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. data presence of olmesartan in milk was observed after a single oral administration of 5 mg/kg [ 14 c] olmesartan medoxomil to lactating rats. the antihypertensive effects of olmesartan medoxomil were evaluated in one randomized, double-blind clinical study in pediatric patients 1 to 16 years of age [see clinical studies (14.2)] . the pharmacokinetics of olmesartan medoxomil were evaluated in pediatric patients 1 to 16 years of age [see clinical pharmacology (12.3)] . olmesartan medoxomil was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. olmesartan medoxomil has not been shown to be effective for hypertension in children <6 years of age. use of olmesartan medoxomil in children <1 year of age is not recommended [see warnings and precautions (5.2)]. the renin-angiotensin-aldosterone system (raas) plays a critical role in kidney development. raas blockade has been shown to lead to abnormal kidney development in very young mice. administering drugs that act directly on the renin-angiotensin aldosterone system (raas) can alter normal renal development. of the total number of hypertensive patients receiving olmesartan medoxomil in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. no overall differences in effectiveness or safety were observed between elderly patients and younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)] . increases in auc 0-∞ and c max were observed in patients with moderate hepatic impairment compared to those in matched controls, with an increase in auc of about 60%. no initial dosage adjustment is recommended for patients with moderate to marked hepatic dysfunction [see clinical pharmacology (12.3)] . patients with renal insufficiency have elevated serum concentrations of olmesartan compared to subjects with normal renal function. after repeated dosing, the auc was approximately tripled in patients with severe renal impairment (creatinine clearance <20 ml/min). no initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 ml/min) [see dosage and administration (2.1), warnings and precautions (5.4) and clinical pharmacology (12.3)] . the antihypertensive effect of olmesartan medoxomil was smaller in black patients (usually a low-renin population), as has been seen with ace inhibitors, beta-blockers and other angiotensin receptor blockers.

Spojené štáty - angličtina - NLM (National Library of Medicine)

bryant ranch prepack - olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - olmesartan medoxomil tablets are indicated for the treatment of hypertension in adults and children six years of age and older, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with olmesartan medoxomil. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. it may be used alone or in combination with other antihypertensive agents. do not co-administer aliskiren with olmesartan medoxomil in patients with diabetes [see drug interactions (7.3)]. risk summary olmesartan medoxomil can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. in animal reproduction studies, olmesartan medoxomil treatment during organogenesis resulted in increased embryofetal toxicity in rats at doses lower than maternally toxic doses. when pregnancy is detected, discontinue olmesartan medoxomil as soon as possible. consider alternative antihypertensive therapy during pregnancy. the estimated background risk of major birth defects and miscarriage for the indicated population is 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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. in patients taking olmesartan medoxomil tablets during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to olmesartan medoxomil for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to olmesartan medoximil, if oliguria or hypotension occurs, utilize measures to maintain adequate blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function. data animal data no teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose (mrhd) on a mg/m 2 basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the mrhd on a mg/m 2 basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the does). in rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricula, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥ 8 mg/kg/day. the no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the mrhd of 40 mg/day. risk summary there is no information regarding the presence of olmesartan in human milk, the effects on the breastfed infant, or the effects on milk production. olmesartan is secreted at low concentration in the milk of lactating rats (see data) . because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. data presence of olmesartan in milk was observed after a single oral administration of 5 mg/kg [ 14 c] olmesartan medoxomil to lactating rats. the antihypertensive effects of olmesartan medoxomil were evaluated in one randomized, double-blind clinical study in pediatric patients 1 to 16 years of age [see clinical studies (14.2)] . the pharmacokinetics of olmesartan medoxomil were evaluated in pediatric patients 1 to 16 years of age [see clinical pharmacology (12.3)] . olmesartan medoxomil was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. olmesartan medoxomil has not been shown to be effective for hypertension in children <6 years of age. use of olmesartan medoxomil in children <1 year of age is not recommended [see warnings and precautions (5.2)]. the renin-angiotensin-aldosterone system (raas) plays a critical role in kidney development. raas blockade has been shown to lead to abnormal kidney development in very young mice. administering drugs that act directly on the renin-angiotensin aldosterone system (raas) can alter normal renal development. of the total number of hypertensive patients receiving olmesartan medoxomil in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. no overall differences in effectiveness or safety were observed between elderly patients and younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)] . increases in auc 0-∞ and c max were observed in patients with moderate hepatic impairment compared to those in matched controls, with an increase in auc of about 60%. no initial dosage adjustment is recommended for patients with moderate to marked hepatic dysfunction [see clinical pharmacology (12.3)] . patients with renal insufficiency have elevated serum concentrations of olmesartan compared to subjects with normal renal function. after repeated dosing, the auc was approximately tripled in patients with severe renal impairment (creatinine clearance <20 ml/min). no initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 ml/min) [see dosage and administration (2.1), warnings and precautions (5.4) and clinical pharmacology (12.3)] . the antihypertensive effect of olmesartan medoxomil was smaller in black patients (usually a low-renin population), as has been seen with ace inhibitors, beta-blockers and other angiotensin receptor blockers.

Spojené štáty - angličtina - NLM (National Library of Medicine)

bryant ranch prepack - olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - olmesartan medoxomil tablets are indicated for the treatment of hypertension in adults and children six years of age and older, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with olmesartan medoxomil. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. it may be used alone or in combination with other antihypertensive agents. do not co-administer aliskiren with olmesartan medoxomil in patients with diabetes [see drug interactions (7.3)]. risk summary olmesartan medoxomil can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. in animal reproduction studies, olmesartan medoxomil treatment during organogenesis resulted in increased embryofetal toxicity in rats at doses lower than maternally toxic doses. when pregnancy is detected, discontinue olmesartan medoxomil as soon as possible. consider alternative antihypertensive therapy during pregnancy. the estimated background risk of major birth defects and miscarriage for the indicated population is 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 oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. in patients taking olmesartan medoxomil tablets during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to olmesartan medoxomil for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to olmesartan medoximil, if oliguria or hypotension occurs, utilize measures to maintain adequate blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and supporting renal function. data animal data no teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose (mrhd) on a mg/m 2 basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the mrhd on a mg/m 2 basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the does). in rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricula, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥ 8 mg/kg/day. the no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the mrhd of 40 mg/day. risk summary there is no information regarding the presence of olmesartan in human milk, the effects on the breastfed infant, or the effects on milk production. olmesartan is secreted at low concentration in the milk of lactating rats (see data) . because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. data presence of olmesartan in milk was observed after a single oral administration of 5 mg/kg [ 14 c] olmesartan medoxomil to lactating rats. the antihypertensive effects of olmesartan medoxomil were evaluated in one randomized, double-blind clinical study in pediatric patients 1 to 16 years of age [see clinical studies (14.2)] . the pharmacokinetics of olmesartan medoxomil were evaluated in pediatric patients 1 to 16 years of age [see clinical pharmacology (12.3)] . olmesartan medoxomil was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. olmesartan medoxomil has not been shown to be effective for hypertension in children <6 years of age. use of olmesartan medoxomil in children <1 year of age is not recommended [see warnings and precautions (5.2)]. the renin-angiotensin-aldosterone system (raas) plays a critical role in kidney development. raas blockade has been shown to lead to abnormal kidney development in very young mice. administering drugs that act directly on the renin-angiotensin aldosterone system (raas) can alter normal renal development. of the total number of hypertensive patients receiving olmesartan medoxomil in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. no overall differences in effectiveness or safety were observed between elderly patients and younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)] . increases in auc 0-∞ and c max were observed in patients with moderate hepatic impairment compared to those in matched controls, with an increase in auc of about 60%. no initial dosage adjustment is recommended for patients with moderate to marked hepatic dysfunction [see clinical pharmacology (12.3)] . patients with renal insufficiency have elevated serum concentrations of olmesartan compared to subjects with normal renal function. after repeated dosing, the auc was approximately tripled in patients with severe renal impairment (creatinine clearance <20 ml/min). no initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 ml/min) [see dosage and administration (2.1), warnings and precautions (5.4) and clinical pharmacology (12.3)] . the antihypertensive effect of olmesartan medoxomil was smaller in black patients (usually a low-renin population), as has been seen with ace inhibitors, beta-blockers and other angiotensin receptor blockers.