Estados Unidos - inglês - NLM (National Library of Medicine)

aphena pharma solutions - tennessee, llc - metoprolol succinate (unii: th25pd4ccb) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 50 mg - metoprolol succinate extended-release tablets usp are indicated for the treatment of hypertension. it may be used alone or in combination with other antihypertensive agents [see dosage and administration (2) ] . metoprolol succinate extended-release tablets usp are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol succinate extended-release tablets usp are indicated for the treatment of stable, symptomatic (nyha class ii or iii) heart failure of ischemic, hypertensive, or cardiomyopathic origin. it was studied in patients already receiving ace inhibitors, diuretics, and, in the majority of cases, digitalis. in this population, metoprolol succinate extended-release tablets decreased the rate of mortality plus hospitalization, largely through a reduction in cardiovascular mortality and hospitalizations for heart failure. metoprolol succinate extended-release is contraindicated in severe bradycardia, second or third degree heart block

Estados Unidos - inglês - NLM (National Library of Medicine)

ncs healthcare of ky, llc dba vangard labs - metoprolol succinate (unii: th25pd4ccb) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 25 mg - metoprolol succinate extended-release 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 succinate extended-release tablets may be administered with other antihypertensive agents. metoprolol succinate extended-release tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol succinate extended-release tablets are indicated to reduce the risk of cardiovascular mortality and heart-failure hospitalization in patients with heart failure. metoprolol succinate extended-release tablets are contraindicated in severe bradycardia, second- or third-degree heart block, cardiogenic shock, 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   untreated hypertension and heart failure 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) . 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 24 times the daily dose of 200 mg in a 60 kg patient on a mg/m2 basis. 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. stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. there is a risk for preterm birth with pregnant women with chronic heart failure in 3rd trimester of pregnancy. 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 definitively 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., 24 times, on a mg/m2 basis, the daily dose of 200 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., 10 times, the daily dose of 200 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 monitor the breastfed infant for bradycardia and other symptoms of beta-blockade such as listlessness (hypoglycemia). data based on published case reports, the estimated infant daily dose of metoprolol received from breast milk range 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-hydroxy metoprolol 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. no evidence of impaired fertility due to metoprolol was observed in rats [see nonclinical toxicology (13.1)]. one hundred forty-four hypertensive pediatric patients aged 6 to 16 years were randomized to placebo or to one of three dose levels of metoprolol succinate extended-release (0.2, 1 or 2 mg/kg once daily) and followed for 4 weeks. the study did not meet its primary endpoint (dose response for reduction in sbp). some pre-specified secondary endpoints demonstrated effectiveness including: - dose-response for reduction in dbp, - 1 mg/kg vs. placebo for change in sbp, and - 2 mg/kg vs. placebo for change in sbp and dbp. the mean placebo corrected reductions in sbp ranged from 3 to 6 mmhg, and dbp from 1 to 5 mmhg. mean reduction in heart rate ranged from 5 to 7 bpm but considerably greater reductions were seen in some individuals [see dosage and administration ( 2.1)].   no clinically relevant differences in the adverse event profile were observed for pediatric patients aged 6 to 16 years as compared with adult patients. safety and effectiveness of metoprolol succinate extended-release tablets have not been established in patients <6 years of age. clinical studies of metoprolol succinate extended-release 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. of the 1,990 patients with heart failure randomized to metoprolol succinate extended-release in the merit-hf trial, 50% (990) were 65 years of age and older and 12% (238) were 75 years of age and older. there were no notable differences in efficacy or the rate of adverse reactions between older 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 succinate extended-release in patients with hepatic impairment. because metoprolol succinate extended-release 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)]. 

Estados Unidos - inglês - NLM (National Library of Medicine)

rebel distributors corp - metoprolol succinate (unii: th25pd4ccb) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 50 mg - metoprolol succinate extended-release tablets usp are indicated for the treatment of hypertension. it may be used alone or in combination with other antihypertensive agents [see dosage and administration (2) ] . metoprolol succinate extended-release tablets usp are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol succinate extended-release tablets usp are indicated for the treatment of stable, symptomatic (nyha class ii or iii) heart failure of ischemic, hypertensive, or cardiomyopathic origin. it was studied in patients already receiving ace inhibitors, diuretics, and, in the majority of cases, digitalis. in this population, metoprolol succinate extended-release tablets decreased the rate of mortality plus hospitalization, largely through a reduction in cardiovascular mortality and hospitalizations for heart failure. metoprolol succinate extended-release is contraindicated in severe bradycardia, second or third degree heart block

Estados Unidos - inglês - NLM (National Library of Medicine)

golden state medical supply, inc. - metoprolol succinate (unii: th25pd4ccb) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 100 mg - metoprolol succinate extended-release tablets, usp 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 pharmaco

Estados Unidos - inglês - NLM (National Library of Medicine)

dispensing solutions, inc. - metoprolol succinate (unii: th25pd4ccb) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 50 mg - metoprolol succinate extended-release tablets usp are indicated for the treatment of hypertension. it may be used alone or in combination with other antihypertensive agents [see dosage and administration (2) ] . metoprolol succinate extended-release tablets usp are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol succinate extended-release tablets usp are indicated for the treatment of stable, symptomatic (nyha class ii or iii) heart failure of ischemic, hypertensive, or cardiomyopathic origin. it was studied in patients already receiving ace inhibitors, diuretics, and, in the majority of cases, digitalis. in this population, metoprolol succinate extended-release tablets decreased the rate of mortality plus hospitalization, largely through a reduction in cardiovascular mortality and hospitalizations for heart failure. metoprolol succinate extended-release is contraindicated in severe bradycardia, second or third degree heart block

Estados Unidos - inglês - NLM (National Library of Medicine)

aidarex pharmaceuticals llc - metoprolol succinate (unii: th25pd4ccb) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 25 mg - metoprolol succinate extended-release 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

Estados Unidos - inglês - NLM (National Library of Medicine)

nucare pharmaceuticals,inc. - metoprolol succinate (unii: th25pd4ccb) (metoprolol - unii:geb06nhm23) - metoprolol tartrate 50 mg - metoprolol succinate extended-release tablets, usp 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 pharmaco

Estados Unidos - inglês - NLM (National Library of Medicine)

ani pharmaceuticals, inc. - erythromycin ethylsuccinate (unii: 1014ksj86f) (erythromycin - unii:63937kv33d) - erythromycin 200 mg in 5 ml - to reduce the development of drug-resistant bacteria and maintain the effectiveness of erythromycin ethylsuccinate and other antibacterial drugs, erythromycin ethylsuccinate should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. erythromycin ethylsuccinate for oral suspension usp is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the diseases listed below: upper respiratory tract infections of mild to moderate degree caused by streptococcus pyogenes, streptococcus pneumoniae, or haemophilus influenzae (when used concomitantly with adequate doses of sulfonamides, since many strains of h. influenzae are not susceptible to the erythromycin concentrations ordinarily achieved). (see appropriate sulfonamide labeling for prescribing information.) lower-respiratory tract infections of mild to moderate severity caused by streptococcus pneumonia or streptococcus pyogenes . listeriosis caused by listeria monocytogenes . pertussis (whooping cough) caused by bordetella pertussis . erythromycin is effective in eliminating the organism from the nasopharynx of infected individuals rendering them noninfectious. some clinical studies suggest that erythromycin may be helpful in the prophylaxis of pertussis in exposed susceptible individuals. respiratory tract infections due to mycoplasma pneumoniae . skin and skin structure infections of mild to moderate severity caused by streptococcus pyogenes or staphylococcus aureus (resistant staphylococci may emerge during treatment). diphtheria: infections due to corynebacterium diphtheriae , as an adjunct to antitoxin, to prevent establishment of carriers and to eradicate the organism in carriers. erythrasma: in the treatment of infections due to corynebacterium minutissimum . intestinal amebiasis caused by entamoeba histolytica (oral erythromycins only). extraenteric amebiasis requires treatment with other agents. acute pelvic inflammatory disease caused by neisseria gonorrhoeae : as an alternative drug in treatment of acute pelvic inflammatory disease caused by n. gonorrhoeae in female patients with a history of sensitivity to penicillin. patients should have a serologic test for syphilis before receiving erythromycin as treatment of gonorrhea and a follow-up serologic test for syphilis after 3 months. syphilis caused by treponema pallidum : erythromycin is an alternate choice of treatment for primary syphilis in patients allergic to the penicillins. in treatment of primary syphilis, spinal fluid examinations should be done before treatment and as part of follow-up after therapy. erythromycins are indicated for the treatment of the following infections caused by chlamydia trachomatis : conjunctivitis of the newborn, pneumonia of infancy, and urogenital infections during pregnancy. when tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of uncomplicated urethral, endocervical, or rectal infections in adults due to chlamydia trachomatis . when tetracyclines are contraindicated or not tolerated, erythromycin is indicated for the treatment of nongonococcal urethritis caused by ureaplasma urealyticum . legionnaires' disease caused by legionella pneumophila . although no controlled clinical efficacy studies have been conducted, in vitro and limited preliminary clinical data suggest that erythromycin may be effective in treating legionnaires' disease. prophylaxis prevention of initial attacks of rheumatic fever penicillin is considered by the american heart association to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of streptococcus pyogenes infections of the upper respiratory tract, e.g., tonsillitis or pharyngitis). erythromycin is indicated for the treatment of penicillin-allergic patients.1 the therapeutic dose should be administered for 10 days. prevention of recurrent attacks of rheumatic fever penicillin or sulfonamides are considered by the american heart association to be the drugs of choice in the prevention of recurrent attacks of rheumatic fever. in patients who are allergic to penicillin and sulfonamides, oral erythromycin is recommended by the american heart association in the long-term prophylaxis of streptococcal pharyngitis (for the prevention of recurrent attacks of rheumatic fever).1 erythromycin is contraindicated in patients with known hypersensitivity to this antibiotic. erythromycin is contraindicated in patients taking terfenadine, astemizole, pimozide, or cisapride. (see precautions - drug interactions .) do not use erythromycin concomitantly with hmg coa reductase inhibitors (statins) that are extensively metabolized by cyp 3a4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis.

Estados Unidos - inglês - NLM (National Library of Medicine)

rebel distributors corp - sumatriptan succinate (unii: j8bdz68989) (sumatriptan - unii:8r78f6l9vo), naproxen sodium (unii: 9tn87s3a3c) (naproxen - unii:57y76r9atq) - sumatriptan succinate 85 mg - treximet is indicated for the acute treatment of migraine attacks with or without aura in adults. carefully consider the potential benefits and risks of treximet and other treatment options when deciding to use treximet. treximet is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see contraindications). safety and effectiveness of treximet have not been established for cluster headache. treximet should not be given to patients with history, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes. in addition, patients with other significant underlying cardiovascular diseases should not receive treximet, nor should patients who have had coronary artery bypass graft (cabg) surgery. ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable angina of effort and vasospastic forms of angina, such as the prinzmetal variant), all forms of myocardial infarction, and silent

Estados Unidos - inglês - NLM (National Library of Medicine)

breckenridge pharmaceutical, inc - desvenlafaxine succinate (unii: zb22enf0xr) (desvenlafaxine - unii:ng99554anw) - desvenlafaxine 50 mg - desvenlafaxine is indicated for the treatment of adults with major depressive disorder (mdd) [see clinical studies (14)] . • hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine extended-release tablets formulation. angioedema has been reported in patients treated with desvenlafaxine [see adverse reactions (6.1)] . • the use of maois intended to treat psychiatric disorders with desvenlafaxine or within 7 days of stopping treatment with desvenlafaxine is contraindicated because of an increased risk of serotonin syndrome. the use of desvenlafaxine within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.7) and warnings and precautions (5.2)]. • starting desvenlafaxine in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.8) and warnings and precautions (5.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185. risk summary   based on data from published observational studies, exposure to snris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.4) and clinical considerations] . there are no published studies on desvenlafaxine in pregnant women; however published epidemiologic studies of pregnant women exposed to venlafaxine, the parent compound, have not reported a clear association with adverse developmental outcomes (see data) . there are risks associated with untreated depression in pregnancy and with exposure to snris and ssris, including desvenlafaxine, during pregnancy (see clinical considerations). in reproductive developmental studies in rats and rabbits treated with desvenlafaxine succinate, there was no evidence of teratogenicity at a plasma exposure (auc) that is up to 19-times (rats) and 0.5-times (rabbits) the exposure at an adult human dose of 100 mg per day. however, fetotoxicity and pup deaths were observed in rats at 4.5-times the auc exposure observed with an adult human dose of 100 mg per day. 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 a prospective longitudinal study of 201 women with a history of major depression who were euthymic at the beginning of pregnancy, showed that women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication. maternal adverse reactions exposure to desvenlafaxine in mid to late pregnancy may increase the risk for preeclampsia, and exposure to desvenlafaxine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.4)]. fetal/neonatal adverse reactions exposure to snris or ssris in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding. monitor neonates who were exposed to desvenlafaxine in the third trimester of pregnancy for drug discontinuation syndrome (see data). data human data published epidemiological studies of pregnant women exposed to the parent compound venlafaxine have not reported a clear association with major birth defects or miscarriage. methodological limitations of these observational studies include possible exposure and outcome misclassification, lack of adequate controls, adjustment for confounders, and confirmatory studies; therefore, these studies cannot establish or exclude any drug-associated risk during pregnancy. retrospective cohort studies based on claims data have shown an association between venlafaxine use and preeclampsia, compared to depressed women who did not take an antidepressant during pregnancy. one study that assessed venlafaxine exposure in the second trimester or first half of the third trimester and preeclampsia showed an increased risk compared to unexposed depressed women [adjusted (adj) rr 1.57, 95% ci 1.29 to 1.91]. preeclampsia was observed at venlafaxine doses equal to or greater than 75 mg/day and a duration of treatment >30 days. another study that assessed venlafaxine exposure in gestational weeks 10 to 20 and preeclampsia showed an increased risk at doses equal to or greater than 150 mg/day. available data are limited by possible outcome misclassification and possible confounding due to depression severity and other confounders. retrospective cohort studies based on claims data have suggested an association between venlafaxine use near the time of delivery or through delivery and postpartum hemorrhage. one study showed an increased risk for postpartum hemorrhage when venlafaxine exposure occurred through delivery, compared to unexposed depressed women [adj rr 2.24 (95% ci 1.69 to 2.97)]. there was no increased risk in women who were exposed to venlafaxine earlier in pregnancy. limitations of this study include possible confounding due to depression severity and other confounders. another study showed an increased risk for postpartum hemorrhage when snri exposure occurred for at least 15 days in the last month of pregnancy or through delivery, compared to unexposed women (adj rr 1.64 to 1.76). the results of this study may be confounded by the effects of depression. neonates exposed to snris or ssris, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.2)] . animal data when desvenlafaxine succinate was administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 300 mg/kg/day and 75 mg/kg/day, respectively, no teratogenic effects were observed. these doses were associated with a plasma exposure (auc) 19 times (rats) and 0.5 times (rabbits) the auc exposure at an adult human dose of 100 mg per day. however, fetal weights were decreased and skeletal ossification was delayed in rats in association with maternal toxicity at the highest dose, with an auc exposure at the no-effect dose that is 4.5-times the auc exposure at an adult human dose of 100 mg per day. when desvenlafaxine succinate was administered orally to pregnant rats throughout gestation and lactation, there was a decrease in pup weights and an increase in pup deaths during the first four days of lactation at the highest dose of 300 mg/kg/day. the cause of these deaths is not known. the auc exposure at the no-effect dose for rat pup mortality was 4.5-times the auc exposure at an adult human dose of 100 mg per day. post-weaning growth and reproductive performance of the progeny were not affected by maternal treatment with desvenlafaxine succinate at exposures 19 times the auc exposure at an adult human dose of 100 mg per day. risk summary available limited data from published literature show low levels of desvenlafaxine in human milk, and have not shown adverse reactions in breastfed infants (see data) . there are no data on the effects of desvenlafaxine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for desvenlafaxine and any potential adverse effects on the breastfed child from desvenlafaxine or from the underlying maternal condition. data a lactation study was conducted in 10 breastfeeding women (at a mean of 4.3 months post-partum) who were being treated with a 50 to 150 mg daily dose of desvenlafaxine for postpartum depression. sampling was performed at steady state (up to 8 samples) over a 24 hour dosing period, and included foremilk and hindmilk. the mean relative infant dose was calculated to be 6.8% (range of 5.5 to 8.1%). no adverse reactions were seen in the infants. the safety and effectiveness of desvenlafaxine have not been established in pediatric patients for the treatment of mdd.  efficacy was not demonstrated in two adequate and well controlled, 8-week, randomized, double-blind, placebo-controlled, parallel group studies conducted in 587 patients (7 to 17 years of age) for the treatment of mdd. antidepressants, such as desvenlafaxine, increase the risk of suicidal thoughts and behaviors in pediatric patients [see the boxed warning and warnings and precautions (5.1)] . desvenlafaxine was associated with a decrease in body weight in placebo-controlled trials in pediatric patients with mdd. the incidence of weight loss (≥3.5% of baseline weight) was 22%, 14%, and 7% for patients treated with low dose desvenlafaxine, high dose desvenlafaxine, and placebo, respectively. the risks associated with longer term desvenlafaxine use were assessed in 6-month, open-label extension studies in pediatric patients (7 to 17 years of age) with mdd. pediatric patients (7 to 17 years of age) had mean changes in weight that approximated expected changes, based on data from age- and sex-matched peers. in clinical trials, when compared to adult patients receiving the same dose of desvenlafaxine, exposure to desvenlafaxine was similar in adolescent patients 12 to 17 years of age, and was about 30% higher in pediatric patients 7 to 11 years of age. juvenile animal studies in a juvenile animal study, male and female rats were treated with desvenlafaxine (75, 225 and 675 mg/kg/day) starting on postnatal day (pnd) 22 through 112. behavioral deficits (longer time immobile in a motor activity test, longer time swimming in a straight channel test, and lack of habituation in an acoustic startle test) were observed in males and females but were reversed after a recovery period. a no adverse effect level (noael) was not identified for these deficits. the low adverse effect level (loael) was 75 mg/kg/day which was associated with plasma exposure (auc) twice the levels measured with a pediatric dose of 100 mg/day. in a second juvenile animal study, male and female rats were administered desvenlafaxine (75, 225 or 675 mg/kg/day) for 8 to 9 weeks starting on pnd 22 and were mated with naïve counterparts. delays in sexual maturation and decreased fertility, number of implantation sites and total live embryos were observed in treated females at all doses. the loael for these findings is 75 mg/kg/day which was associated with an auc twice the levels measured with a pediatric dose of 100 mg/day. these findings were reversed at the end of a 4-week recovery period. the relevance of these findings to humans is not known. of the 4,158 patients in pre-marketing clinical studies with desvenlafaxine, 6% were 65 years of age or older. no overall differences in safety or efficacy were observed between these patients and younger patients; however, in the short-term placebo-controlled studies, there was a higher incidence of systolic orthostatic hypotension in patients ≥65 years of age compared to patients <65 years of age treated with desvenlafaxine [see adverse reactions (6.1)] . for elderly patients, possible reduced renal clearance of desvenlafaxine should be considered when determining dose [see dosage and administration (2.2) and clinical pharmacology (12.3)] . ssris and snris, including desvenlafaxine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see warnings and precautions (5.9)] . adjust the maximum recommended dosage in patients with moderate or severe renal impairment (clcr 15 to 50 ml/min, c-g), or end-stage renal disease (clcr < 15 ml/min, c-g) [see dosage and administration (2.2) and clinical pharmacology (12.3)] . adjust the maximum recommended dosage in patients with moderate to severe hepatic impairment (child-pugh score 7 to 15) [see dosage and administration (2.3) and clinical pharmacology (12.3)] . desvenlafaxine is not a controlled substance.