Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

bayer cropscience pty ltd - ethoprophos - unknown - ethoprophos organophosphorus active 0.0 - active constituent

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

bayer cropscience pty ltd - ethoprophos - mixed function pesticide - banana | cereal crop | maize | sugar cane | tobacco | barley | corn | incl.interplanted with avocado | inter-row spraying | maiz - banana weevil borer | blacksoil scarab | bundaberg canegrub | burrowing nematode - radopholus spp. | canegrub - lepidiota negatoria | canegrub - lepidiota picticollis | french's canegrub | root knot nematode | root lesion nematode | southern one-year canegrub | spiral nematode | stubby root nematode | sugarcane wireworm - agrypnus variabilis | wheat root scarab | wireworm | negatoria canegrub | picticollis canegrub | southern 1 year canegrub

Australia - English - APVMA (Australian Pesticides and Veterinary Medicines Authority)

bayer cropscience pty ltd - ethoprophos - nematicide - tobacco - root knot nematode | stubby root nematode

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

hospira, inc. - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 1 mg in 1 ml - metoprolol tartrate injection is indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used in conjunction with oral metoprolol tartrate maintenance therapy. treatment with intravenous metoprolol tartrate can be initiated as soon as the patient's clinical condition allows (see dosage and administration,  contraindications , and warnings ). hypersensitivity to metoprolol tartrate and related derivatives, or to any of the excipients; hypersensitivity to other beta-blockers (cross sensitivity between beta-blockers can occur). metoprolol tartrate is contraindicated in patients with a heart rate <45 beats/min; second- and third-degree heart block; significant first-degree heart block (p-r interval ≥0.24 sec); systolic blood pressure <100 mmhg; or moderate-to-severe cardiac failure (see warnings ).

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

aurobindo pharma limited - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 25 mg - metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal 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 metoprolol. 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. metoprolol tartrate tablets may be administered with other antihypertensive agents. metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol. metoprolol tartrate tablets are contraindicated in severe bradycardia, second- or third-degree heart block, cardiogenic shock, systolic blood pressure <100, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product. risk summary available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol during pregnancy ( see data). untreated hypertension and myocardial infarction during pregnancy can lead to adverse outcomes for the mother and the fetus (see clinical considerations). in animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 11 times the daily dose of 450 mg in a 60-kg patient on a mg/m2 basis. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 consideration 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 metoprolol crosses the placenta. neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. observe neonates and manage accordingly. data human data data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol in pregnancy. the published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. animal data metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e., 11 times, on a mg/m2 basis, the daily dose of 450 mg in a 60-kg patient. no fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e., 4 times, the daily dose of 400 mg in a 60-kg patient. risk summary limited available data from published literature report that metoprolol is present in human milk. the estimated daily infant dose of metoprolol received from breastmilk ranges from 0.05 mg to less than 1 mg. the estimated relative infant dosage was 0.5% to 2% of the mother's weight-adjusted dosage (see data). no adverse reactions of metoprolol on the breastfed infant have been identified. there is no information regarding the effects of metoprolol on milk production. clinical consideration monitoring for adverse reactions for a lactating woman who is a slow metabolizer of metoprolol, monitor the breastfed infant for bradycardia and other symptoms of beta-blockade such as dry mouth, skin or eyes, diarrhea or constipation. in a report of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant. data limited published cases estimate the infant daily dose of metoprolol received from breast milk range from 0.05 mg to less than 1 mg. in 2 women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. the estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. in a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. the average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17 to 158.7). the average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. risk summary based on the published literature, beta-blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. in animal fertility studies, metoprolol has been associated with reversible adverse effects on spermatogenesis starting at oral dose level of 3.5 mg/kg in rats, which would correspond to a dose of 34 mg/day in humans in mg/m2 equivalent, although other studies have shown no effect of metoprolol on reproductive performance in male rats. no evidence of impaired fertility due to metoprolol was observed in rats [see nonclinical toxicology (13.1)]. safety and effectiveness of metoprolol have not been established in pediatric patients. clinical studies of metoprolol in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. in worldwide clinical trials of metoprolol in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. in general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. no studies have been performed with metoprolol in patients with hepatic impairment. because metoprolol is metabolized by the liver, metoprolol blood levels are likely to increase substantially with poor hepatic function. therefore, initiate therapy at doses lower than those recommended for a given indication; and increase doses gradually in patients with impaired hepatic function. the systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. no reduction in dosage is needed in patients with chronic renal failure [see clinical pharmacology (12.3)].

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

remedyrepack inc. - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 50 mg - metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal 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 metoprolol. 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. metoprolol tartrate tablets may be administered with other antihypertensive agents. metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol. metoprolol tartrate tablets are contraindicated in severe bradycardia, second or third degree heart block, cardiogenic shock, systolic blood pressure <100, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product. available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol during pregnancy ( see data). untreated hypertension and myocardial infarction during pregnancy can lead to adverse outcomes for the mother and the fetus (see clinical considerations). in animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 11 times the daily dose of 450 mg in a 60-kg patient on a mg/m 2 basis. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. metoprolol crosses the placenta. neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. observe neonates and manage accordingly. data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol in pregnancy. the published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e., 11 times, on a mg/m 2 basis, the daily dose of 450 mg in a 60-kg patient. no fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e., 4 times, the daily dose of 400mg in a 60-kg patient. limited available data from published literature report that metoprolol is present in human milk. the estimated daily infant dose of metoprolol received from breastmilk ranges from 0.05 mg to less than 1 mg. the estimated relative infant dosage was 0.5% to 2% of the mother's weight-adjusted dosage (see data). no adverse reactions of metoprolol on the breastfed infant have been identified. there is no information regarding the effects of metoprolol on milk production. for a lactating woman who is a slow metabolizer of metoprolol, monitor the breastfed infant for bradycardia and other symptoms of beta blockade such as dry mouth, skin or eyes, diarrhea or constipation. in a report of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant. limited published cases estimate the infant daily dose of metoprolol received from breast milk range from 0.05 mg to less than 1 mg. in 2 women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. the estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. in a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. the average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17.0 to 158.7). the average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. based on the published literature, beta blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. in animal fertility studies, metoprolol has been associated with reversible adverse effects on spermatogenesis starting at oral dose level of 3.5 mg/kg in rats, which would correspond to a dose of 34 mg/day in humans in mg/m 2 equivalent, although other studies have shown no effect of metoprolol on reproductive performance in male rats. no evidence of impaired fertility due to metoprolol was observed in rats [see nonclinical toxicology (13.1)]. safety and effectiveness of metoprolol tartrate tablets have not been established in pediatric patients. clinical studies of metoprolol tartrate tablets in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. in worldwide clinical trials of metoprolol tartrate tablets in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. in general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. no studies have been performed with metoprolol tartrate tablets in patients with hepatic impairment. because metoprolol tartrate tablets are metabolized by the liver, metoprolol blood levels are likely to increase substantially with poor hepatic function. therefore, initiate therapy at doses lower than those recommended for a given indication; and increase doses gradually in patients with impaired hepatic function. the systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. no reduction in dosage is needed in patients with chronic renal failure [see clinical pharmacology (12.3)].

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

mylan pharmaceuticals inc. - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 25 mg - metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal 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 metoprolol. 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. metoprolol tartrate tablets may be administered with other antihypertensive agents. metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol. metoprolol tartrate tablets are contraindicated in severe bradycardia, second- or third-degree heart block, cardiogenic shock, systolic blood pressure <100, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product. available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol during pregnancy (see data) . untreated hypertension and myocardial infarction during pregnancy can lead to adverse outcomes for the mother and the fetus (see clinical considerations) . in animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 11 times the daily dose of 450 mg in a 60-kg patient on a mg/m2 basis. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. metoprolol crosses the placenta. neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. observe neonates and manage accordingly. data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol in pregnancy. the published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e., 11 times, on a mg/m2 basis, the daily dose of 450 mg in a 60-kg patient. no fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e., 4 times, the daily dose of 400mg in a 60-kg patient. limited available data from published literature report that metoprolol is present in human milk. the estimated daily infant dose of metoprolol received from breastmilk ranges from 0.05 mg to less than 1 mg. the estimated relative infant dosage was 0.5% to 2% of the mother's weight-adjusted dosage (see data) . no adverse reactions of metoprolol on the breastfed infant have been identified. there is no information regarding the effects of metoprolol on milk production. for a lactating woman who is a slow metabolizer of metoprolol, monitor the breastfed infant for bradycardia and other symptoms of beta-blockade such as dry mouth, skin or eyes, diarrhea or constipation. in a report of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant. limited published cases estimate the infant daily dose of metoprolol received from breast milk range from 0.05 mg to less than 1 mg. in 2 women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. the estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. in a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. the average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17.0 to 158.7). the average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. based on the published literature, beta-blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. in animal fertility studies, metoprolol has been associated with reversible adverse effects on spermatogenesis starting at oral dose level of 3.5 mg/kg in rats, which would correspond to a dose of 34 mg/day in humans in mg/m2 equivalent, although other studies have shown no effect of metoprolol on reproductive performance in male rats. no evidence of impaired fertility due to metoprolol was observed in rats [see nonclinical toxicology (13.1)] . safety and effectiveness of metoprolol tartrate tablets have not been established in pediatric patients. clinical studies of metoprolol tartrate tablets in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. in worldwide clinical trials of metoprolol tartrate tablets in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. in general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. no studies have been performed with metoprolol tartrate tablets in patients with hepatic impairment. because metoprolol tartrate tablets are metabolized by the liver, metoprolol blood levels are likely to increase substantially with poor hepatic function. therefore, initiate therapy at doses lower than those recommended for a given indication; and increase doses gradually in patients with impaired hepatic function. the systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. no reduction in dosage is needed in patients with chronic renal failure [see clinical pharmacology (12.3)].

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

mylan pharmaceuticals inc. - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - metoprolol tartrate 50 mg - metoprolol tartrate and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal 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 metoprolol. 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. metoprolol tartrate and hydrochlorothiazide tablets may be administered with other antihypertensive agents. limitation of use:  metoprolol tartrate and hydrochlorothiazide tablets are not indicated for initial therapy of hypertension. if the fixed combination represents the dose titrated to the individual patient’s needs, therapy with the fixed combination may be more convenient than with the separate components. metoprolol tartrate and hydrochlorothiazide tablets are contraindicated in patients with: untreated hypertension during pregnancy can lead to adverse outcomes for the mother and the fetus (see clinical considerations) . available data from published observational studies have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with metoprolol use during pregnancy. however, there are inconsistent reports of intrauterine growth restriction, preterm birth, and perinatal mortality with maternal use of beta blockers, including metoprolol, during pregnancy (see data) . there have been rare reports of jaundice, thrombocytopenia, and electrolyte imbalances in infants exposed to thiazide medications during pregnancy. in animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages up to 24 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. the combination of metoprolol tartrate/hydrochlorothiazide administered to rats from mid-late gestation through lactation also produced increased post-implantation loss and decreased neonatal survival (see data) . 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. 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. metoprolol metoprolol crosses the placenta. neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. observe neonates for symptoms of hypotension, bradycardia, hypoglycemia and respiratory depression and manage accordingly. data from published observational studies did not demonstrate an association of major congenital malformations and use of either metoprolol or hydrochlorothiazide in pregnancy. the published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. oral administration of metoprolol tartrate/hydrochlorothiazide combinations to pregnant rats during organogenesis at doses up to 200/50 mg/kg/day (10 and 20 times the mrhd on a mg/m2 basis for metoprolol and hydrochlorothiazide, respectively) or to pregnant rabbits at doses up to 25/6.25 mg/kg/day (about 2.5 and 5 times the mrhd on a mg/m2 basis for metoprolol and hydrochlorothiazide, respectively) produced no teratogenic effects. a 200/50 mg/kg/day metoprolol tartrate/hydrochlorothiazide combination administered to rats from mid-late gestation through lactation produced increased post-implantation loss and decreased neonatal survival. metoprolol metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at doses up to 24 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. distribution studies in mice confirm exposure of the fetus when metoprolol tartrate is administered to the pregnant animal. these studies have revealed no evidence of impaired fertility or teratogenicity. hydrochlorothiazide hydrochlorothiazide administered to pregnant mice and rats during organogenesis at doses up to 3000 and 1000 mg/kg/day (600 and 400 times the mrhd on a mg/m2 basis), respectively, produced no harm to the fetus. thiazides cross the placental barrier and appear in the cord blood. there are no data on the presence of metoprolol tartrate and hydrochlorothiazide in human milk, the effects on the breastfed infant, or the effects on milk production. however, data are available on the individual components of metoprolol tartrate and hydrochlorothiazide tablets. available data from published literature on metoprolol and hydrochlorothiazide report that each drug is present in human milk (see data) . there are no reports of adverse effects on breastfed infants exposed to metoprolol or hydrochlorothiazide during lactation. doses of hydrochlorothiazide associated with clinically significant diuresis have been associated with impaired milk production. there is no information regarding the effects of metoprolol on milk production. monitor infants exposed to metoprolol tartrate and hydrochlorothiazide tablets though breastmilk for drowsiness or poor feeding (see clinical considerations ) . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for metoprolol tartrate and hydrochlorothiazide tablets and any potential adverse effects on the breastfed child from metoprolol tartrate and hydrochlorothiazide tablets or from the underlying maternal condition. monitor the breastfed infant for bradycardia or somnolence. based on published case reports, the estimated daily infant dose of metoprolol received from breastmilk ranged from 0.05 mg to less than 1 mg. the estimated relative infant dosage was 0.5% to 2% of the mother’s weight-adjusted dosage. in two women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. the estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. in a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. the average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17.0 to 158.7). the average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. a single study involving one woman and her infant showed a peak concentration of 275 mcg/l at 3 hours following 50 mg dose. no drug was detected (< 20 mcg/l) in the infant’s plasma at 2 and 11 hours following mother’s dose. based on the published literature, beta blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. no evidence of impaired fertility due to metoprolol or hydrochlorothiazide was observed in rats [see nonclinical toxicology (13)] . safety and effectiveness in pediatric patients have not been established. clinical studies of metoprolol tartrate and hydrochlorothiazide tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. hydrochlorothiazide is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. 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 warnings and precautions (5.8)] . in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

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

alembic pharmaceuticals inc. - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 25 mg - metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal 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 metoprolol. 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.  metoprolol tartrate tablets may be administered with other antihypertensive agents. metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol. metoprolol tartrate tablets are contraindicated in severe bradycardia, second-or third-degree heart block, cardiogenic shock, systolic blood pressure <100, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product. risk summary available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol during pregnancy ( see data). untreated hypertension and myocardial infarction during pregnancy can lead to adverse outcomes for the mother and the fetus (see clinical considerations). in animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 11 times the daily dose of 450 mg in a 60­kg patient on a mg/m2 basis. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 consideration   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 metoprolol crosses the placenta. neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. observe neonates and manage accordingly. data   human data data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol in pregnancy. the published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. animal data metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e., 11 times, on a mg/m2 basis, the daily dose of 450 mg in a 60-kg patient. no fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e., 4 times, the daily dose of 400mg in a 60-kg patient. risk summary limited available data from published literature report that metoprolol is present in human milk. the estimated daily infant dose of metoprolol received from breastmilk ranges from 0.05 mg to less than 1 mg. the estimated relative infant dosage was 0.5% to 2% of the mother's weight-adjusted dosage (see data). no adverse reactions of metoprolol on the breastfed infant have been identified. there is no information regarding the effects of metoprolol on milk production. clinical consideration   monitoring for adverse reactions for a lactating woman who is a slow metabolizer of metoprolol, monitor the breastfed infant for bradycardia and other symptoms of beta-blockade such as dry mouth, skin or eyes, diarrhea or constipation. in a report of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant. data limited published cases estimate the infant daily dose of metoprolol received from breast milk range from 0.05 mg to less than 1 mg. in 2 women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. the estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. in a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. the average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17 to 158.7). the average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. risk summary based on the published literature, beta-blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. in animal fertility studies, metoprolol has been associated with reversible adverse effects on spermatogenesis starting at oral dose level of 3.5 mg/kg in rats, which would correspond to a dose of 34 mg/day in humans in mg/m2 equivalent, although other studies have shown no effect of metoprolol on reproductive performance in male rats. no evidence of impaired fertility due to metoprolol was observed in rats [see nonclinical toxicology (13.1)]. safety and effectiveness of metoprolol tartrate have not been established in pediatric patients. clinical studies of metoprolol tartrate in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. in worldwide clinical trials of metoprolol tartrate in myocardial infarction, where approximately 478 patients were over 65years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. in general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. no studies have been performed with metoprolol tartrate in patients with hepatic impairment. because metoprolol tartrate is metabolized by the liver, metoprolol blood levels are likely to increase substantially with poor hepatic function. therefore, initiate therapy at doses lower than those recommended for a given indication; and increase doses gradually in patients with impaired hepatic function. the systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. no reduction in dosage is needed in patients with chronic renal failure [see clinical pharmacology (12.3)].

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

alembic pharmaceuticals inc. - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - metoprolol tartrate 50 mg - metoprolol tartrate and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal 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 metoprolol. 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. metoprolol tartrate and hydrochlorothiazide tablets may be administered with other antihypertensive agents. limitation of use metoprolol tartrate and hydrochlorothiazide tablets are not indicated for initial therapy of hypertension. if the fixed combination represents the dose titrated to the individual patient’s needs, therapy with the fixed combination may be more convenient than with the separate components. metoprolol tartrate and hydrochlorothiazide tablets are contraindicated in patients with: - cardiogenic shock or decompensated heart failure. - sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place. - anuria - hypersensitivity to metoprolol tartrate or hydrochlorothiazide or to other sulfonamide derived drugs. risk summary untreated hypertension during pregnancy can lead to adverse outcomes for the mother and the fetus (see clinical considerations) . available data from published observational studies have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with metoprolol use during pregnancy. however, there are inconsistent reports of intrauterine growth restriction, preterm birth, and perinatal mortality with maternal use of beta blockers, including metoprolol, during pregnancy (see data). there have been rare reports of jaundice, thrombocytopenia, and electrolyte imbalances in infants exposed to thiazide medications during pregnancy. in animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages up to 24 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. the combination of metoprolol tartrate/hydrochlorothiazide administered to rats from mid-late gestation through lactation also produced increased post-implantation loss and decreased neonatal survival (see data) . 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 consideration 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 metoprolol metoprolol crosses the placenta. neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. observe neonates for symptoms of hypotension, bradycardia, hypoglycemia and respiratory depression and manage accordingly.     data   human data data from published observational studies did not demonstrate an association of major congenital malformations and use of either metoprolol or hydrochlorothiazide in pregnancy. the published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. animal data oral administration of metoprolol tartrate/hydrochlorothiazide combinations to pregnant rats during organogenesis at doses up to 200/50 mg/kg/day (10 and 20 times the mrhd on a mg/m2 basis for metoprolol and hydrochlorothiazide, respectively) or to pregnant rabbits at doses up to 25/6.25 mg/kg/day (about 2.5 and 5 times the mrhd on a mg/m2 basis for metoprolol and hydrochlorothiazide, respectively) produced no teratogenic effects. a 200/50 mg/kg/day metoprolol tartrate/hydrochlorothiazide combination administered to rats from mid-late gestation through lactation produced increased post-implantation loss and decreased neonatal survival. metoprolol metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at doses up to 24 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. distribution studies in mice confirm exposure of the fetus when metoprolol tartrate is administered to the pregnant animal. these studies have revealed no evidence of impaired fertility or teratogenicity. hydrochlorothiazide hydrochlorothiazide administered to pregnant mice and rats during organogenesis at doses up to 3000 and 1000 mg/kg/day (600 and 400 times the mrhd on a mg/m2 basis), respectively, produced no harm to the fetus. thiazides cross the placental barrier and appear in the cord blood. risk summary there are no data on the presence of metoprolol tartrate and hydrochlorothiazide in human milk, the effects on the breastfed infant, or the effects on milk production. however, data are available on the individual components of metoprolol tartrate and hydrochlorothiazide. available data from published literature on metoprolol and hydrochlorothiazide report that each drug is present in human milk (see data) . there are no reports of adverse effects on breastfed infants exposed to metoprolol or hydrochlorothiazide during lactation. doses of hydrochlorothiazide associated with clinically significant diuresis have been associated with impaired milk production. there is no information regarding the effects of metoprolol on milk production. monitor infants exposed to metoprolol tartrate and hydrochlorothiazide though breastmilk for drowsiness or poor feeding (see clinical considerations).   the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for metoprolol tartrate and hydrochlorothiazide and any potential adverse effects on the breastfed child from metoprolol tartrate and hydrochlorothiazide or from the underlying maternal condition. clinical considerations monitor the breastfed infant for bradycardia or somnolence. data metoprolol based on published case reports, the estimated daily infant dose of metoprolol received from breastmilk ranged from 0.05 mg to less than 1 mg. the estimated relative infant dosage was 0.5% to 2% of the mother’s weight-adjusted dosage. in two women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. the estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. in a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. the average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17 to 158.7). the average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. hydrochlorothiazide a single study involving one woman and her infant showed a peak concentration of 275 mcg/l at 3 hours following 50 mg dose. no drug was detected (< 20 mcg/l) in the infant’s plasma at 2-and 11-hours following mother’s dose. infertility   males based on the published literature, beta blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. no evidence of impaired fertility due to metoprolol or hydrochlorothiazide was observed in rats [see nonclinical toxicology (13.1)]. safety and effectiveness in pediatric patients have not been established. clinical studies of metoprolol tartrate and hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. hydrochlorothiazide is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. 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 warnings and precautions (5.8)]. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.