Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram tablets are indicated for the treatment of: • major depressive disorder (mdd) in adults and pediatric patients 12 years of age and older. • generalized anxiety disorder (gad) in adults  additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. escitalopram tablets are contraindicated in patients: • taking maois with escitalopram tablets or within 14 days of stopping treatment with escitalopram tablets because of an increased risk of serotonin syndrome. the use of escitalopram tablets 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 escitalopram tablets 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 (2.6), and warnings and precautions (5.2)] . • taking pimozide [see drug interactions (7)] . • with a hypersensitivity to escitalopram or citalopram or any of the inactive ingredients in escitalopram tablets. 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 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. risk summary based on data from published observational studies, exposure to ssris, 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 (5.7) and clinical considerations] . available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage. there are risks of persistent pulmonary hypertension of the newborn (pphn) (see data) and poor neonatal adaptation (see clinical considerations), with exposure to selective serotonin reuptake inhibitors (ssris), including escitalopram, during pregnancy. there are risks associated with untreated depression in pregnancy (see clinical considerations). in animal reproduction studies, both escitalopram and racemic citalopram have been shown to have adverse effects on embryo/fetal and postnatal development, including fetal structural abnormalities, when administered at doses greater than human therapeutic doses (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 the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal risk and/or embryo/fetal risk women who discontinue antidepressants are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective longitudinal study of 201 pregnant women with a history of major depression, who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of escitalopram tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.7)]. fetal/neonatal adverse reactions neonates exposed to ssris or snris, including escitalopram, late in 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)] . data human data exposure to ssris, particularly later in pregnancy, may increase the risk for pphn. pphn occurs in 1 to 2 per 1,000 live births in the general populations and is associated with substantial neonatal morbidity and mortality. animal data in a rat embryo/fetal development study, oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses [approximately ≥ 55 times the maximum recommended human dose (mrhd) of 20 mg/day on a mg/m2 basis]. maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was present at all dose levels. the developmental no-effect dose of 56 mg/kg/day is approximately 27 times the mrhd of 20 mg on a mg/m2 basis. no malformations were observed at any of the doses tested (as high as 73 times the mrhd on a mg/m2 basis). when female rats were treated with escitalopram (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and growth retardation were noted at 48 mg/kg/day which is approximately 23 times the mrhd of 20 mg on a mg/m2  basis.  slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) was seen at this dose.  slightly increased offspring mortality was also seen at 24 mg/kg/day.  the no-effect dose was 12 mg/kg/day which is approximately 6 times the mrhd of 20 mg on a mg/m2 basis. in two rat embryo/fetal development studies, oral administration of racemic citalopram (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose, which is approximately 18 times the mrhd of 60 mg/day on a mg/m2  basis. this dose was also associated with maternal toxicity (clinical signs, decreased body weight gain).  the developmental no-effect dose was 56 mg/kg/day is approximately 9 times the mrhd on a mg/m2 basis.  in a rabbit study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day, or approximately 5 times the mrhd on a mg/m2 basis. thus, developmental effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit. when female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were observed at the highest dose, which is approximately 5 times the mrhd of 60 mg on a mg/m2 basis. the no-effect dose was 12.8 mg/kg/day is approximately 2 times the mrhd on a mg/m2 basis. similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, approximately 4 times the mrhd on a mg/m2 basis. a no-effect dose was not determined in that study. risk summary data from the published literature report the presence of escitalopram and desmethylescitalopram in human milk (see data ). there are reports of excessive sedation, restlessness, agitation, poor feeding and poor weight gain in infants exposed to escitalopram, through breast milk (see clinical considerations) . there are no data on the effects of escitalopram or its metabolites on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for escitalopram and any potential adverse effects on the breastfed child from escitalopram or from the underlying maternal condition. clinical considerations infants exposed to escitalopram should be monitored for excess sedation, restlessness, agitation, poor feeding and poor weight gain. data a study of 8 nursing mothers on escitalopram with daily doses of 10 to 20 mg/day showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram. major depressive disorder the safety and effectiveness of escitalopram for the treatment of major depressive disorder have been established in pediatric patients 12 years of age and older. use of escitalopram for this indication is supported by evidence from adequate and well-controlled studies in adults with additional evidence from an 8-week, flexible-dose, placebo-controlled study that compared escitalopram tablets 10 mg to 20 mg once daily to placebo in pediatric patients 12 to 17 years of age with major depressive disorder [see clinical studies (14.1)] . the safety of escitalopram was similar to adult patients with mdd [see adverse reactions (6.1)] . the safety and effectiveness of escitalopram for the treatment of major depressive disorder have not been established in pediatric patients younger than 12 years of age. in a 24-week, open-label safety study in 118 pediatric patient (aged 7 to 11 years) who had major depressive disorder, the safety findings were consistent with the known safety and tolerability profile for escitalopram. generalized anxiety disorder the safety and effectiveness of escitalopram for the treatment of generalized anxiety disorder have not been established in pediatric patients younger than 7 years of age. antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see warnings and precautions (5.1)] . decreased appetite and weight loss have been observed in association with the use of ssris. consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an ssri such as escitalopram. juvenile animal toxicity data in a juvenile animal study, male and female rats were administered escitalopram at 5, 40, or 80 mg/kg/day by oral gavage from postnatal day (pnd) 21 to pnd 69. a delay in sexual maturation was observed in both males and females at ≥ 40 mg/kg/day with a no observed adverse effect level (noael) of 5 mg/kg/day. this noael was associated with plasma auc levels less than those measured at the maximum recommended dose (mrhd) in pediatrics (20 mg). however, there was no effect on reproductive function. increased motor activity (both ambulatory and fine movements) was observed in females prior to daily dosing at ≥ 40 mg/kg/day (3.5 times the mrhd based on auc levels). a reversible disruption of learning and memory function was observed in males at 80 mg/kg/day with a noael of 40 mg/kg/day, which was associated with an auc level 3.5 times those measured at the mrhd in pediatrics. there was no effect on learning and memory function in treated female rats. additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. approximately 69 patients (6%) of the 1,144 patients receiving escitalopram in controlled trials of escitalopram in major depressive disorder and gad were 60 years of age or older [see clinical studies (14.1, 14.2)] . the number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram cannot be ruled out. in two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in subjects 65 years and older as compared to young subjects and cmax was unchanged [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram tablets for elderly patients is 10 mg daily [see dosage and administration (2.5)] . ssris, including escitalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.6)] . of 4,422 patients in clinical studies of racemic citalopram, 1,357 were 60 and over, 1,034 were 65 and over, and 457 were 75 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the geriatric and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out. increased citalopram exposure occurs in patients with hepatic impairment [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram tablets in patients with hepatic impairment is 10 mg daily [see dosage and administration (2.5)] . pharmacokinetics of escitalopram in patients with a creatinine clearance less than 20 ml/minute has not been evaluated. no dosage adjustment is necessary for patients with mild or moderate renal impairment [see dosage and administration (2.5), clinical pharmacology (12.3)] . physical and psychological dependence animal studies suggest that the abuse liability of racemic citalopram is low. escitalopram has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with escitalopram did not reveal any drug-seeking behavior. however, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate escitalopram patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - bupropion hydrochloride extended-release tablets, usp (sr) are indicated for the treatment of major depressive disorder (mdd), as defined by the diagnostic and statistical manual (dsm) . the efficacy of bupropion in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with mdd [see clinical studies(14)] . the efficacy of bupropion hydrochloride extended-release tablets, usp (sr) in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial [see clinical studies  (14)] . - bupropionhydrochloride extended-release tablets (sr) are contraindicated in patients with a seizure disorder. - bupropion hydrochloride extended-release tablets (sr) arecontraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with the immediate-release formulation of bupropion [see warnings and precautions (5.3)]. - bupropionhydrochloride extended-release tablets (sr) arecontraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see warnings and precautions (5.3), drug interactions (7.3)] . - the use of maois (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride extended-release tablets (sr) or within 14 days of discontinuing treatment with bupropion hydrochloride extended-release tablets (sr) are contraindicated. there is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (sr) are used concomitantly with maois. the use of bupropion hydrochloride extended-release tablets (sr) within 14 days of discontinuing treatment with an maoi is also contraindicated. starting bupropion hydrochloride extended-release tablets (sr) in a patient treated with reversible maois such as linezolid or intravenous methylene blue is contraindicated [see dosage and administration (2.4, 2.5), warnings and precautions (5.4), drug interactions (7.6)]. - bupropion hydrochloride extended-release tablets (sr) are contraindicated in patients with known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release tablets (sr). anaphylactoid/anaphylactic reactions and stevens-johnson syndrome have been reported [see warnings and precautions (5.8)]. pregnancy exposure registry there is an independent pregnancy exposure registry that monitors pregnancy outcomes in women exposed to any antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405­ 6185 or visiting online at https://womensmentalhealth.org/clinical-and-research­programs/pregnancyregistry/antidepressants. risk summary data from epidemiological studies of pregnant women exposed to bupropion in the first trimester have not identified an increased risk of congenital malformations overall (see data) . there are risks to the mother associated with untreated depression in pregnancy (see clinical considerations). when bupropion was administered to pregnant rats during organogenesis, there was no evidence of fetal malformations at doses up to approximately 11 times the maximum recommended human dose (mrhd) of 400 mg/day. when given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations, and skeletal variations were observed at doses approximately equal to the mrhd and greater. decreased fetal weights were seen at doses twice the mrhd and greater (see animal data) . the estimated background risk for major birth defects and miscarriage is unknown for the indicated population. 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 of 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 followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants during pregnancy at the beginning of pregnancy. the women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. consider the risks to the mother of untreated depression and potential effects on the fetus when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. data human data: data from the international bupropion pregnancy registry (675 first trimester exposures) and a retrospective cohort study using the united healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. the registry was not designed or powered to evaluate specific defects but suggested a possible increase in cardiac malformations. no increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. the prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international pregnancy registry was 1.3% (9 cardiovascular malformations/675 first trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). data from the united healthcare database, which had a limited number of exposed cases with cardiovascular malformations, and a case-control study (6,853 infants with cardiovascular malformations and 5,763 with non-cardiovascular malformations) of self-reported bupropion use from the national birth defects prevention study (nbdps) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester. study findings on bupropion exposure during the first trimester and risk for left ventricular outflow tract obstruction (lvoto) are inconsistent and do not allow conclusions regarding a possible association. the united healthcare database lacked sufficient power to evaluate this association; the nbdps found increased risk for lvoto (n = 10; adjusted or = 2.6; 95% ci: 1.2, 5.7), and the slone epidemiology case control study did not find increased risk for lvoto. study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (vsd) are inconsistent and do not allow conclusions regarding a possible association. the slone epidemiology study found an increased risk for vsd following first trimester maternal bupropion exposure (n = 17; adjusted or = 2.5; 95% ci: 1.3, 5.0) but did not find increased risk for any other cardiovascular malformations studied (including lvoto as above). the nbdps and united healthcare database study did not find an association between first trimester maternal bupropion exposure and vsd. for the findings of lvoto and vsd, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. animal data: in studies conducted in pregnant rats and rabbits, bupropion was administered orally during the period of organogenesis at doses of up to 450 and 150 mg/kg/day, respectively (approximately 11 and 7 times the mrhd, respectively, on a mg/m2 basis). there was no evidence of fetal malformations in rats. when given to pregnant rabbits during organogenesis, non-dose–related increases in incidence of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the mrhd on a mg/m2 basis) and greater. decreased fetal weights were observed at doses of 50 mg/kg/day (approximately 2 times the mrhd on a mg/m2 basis) and greater. no maternal toxicity was evident at doses of 50 mg/kg/day or less. in a pre- and postnatal development study, bupropion administered orally to pregnant rats at doses of up to 150 mg/kg/day (approximately 4 times the mrhd on a mg/m2 basis) from embryonic implantation through lactation had no effect on pup growth or development. risk summary data from published literature report the presence of bupropion and its metabolites in human milk (see data) . there are no data on the effects of bupropion or its metabolites on milk production. limited data from postmarketing reports have not identified a clear association of adverse reactions in the breastfed infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for bupropion and any potential adverse effects on the breastfed child from bupropion or from the underlying maternal condition. data in a lactation study of 10 women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. the average daily infant exposure (assuming 150 ml/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. postmarketing reports have described seizures in breastfed infants. the relationship of bupropion exposure and these seizures is unclear. safety and effectiveness in the pediatric population have not been established [see boxed warning, warnings and precautions (5.1)] . of the approximately 6,000 subjects who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation trials), 275 were aged ≥65 years and 47 were aged ≥75 years. in addition, several hundred subjects aged ≥65 years participated in clinical trials using the immediate-release formulation of bupropion (depression trials). no overall differences in safety or effectiveness were observed between these subjects and younger subjects. reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. the risk of adverse reactions may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see dosage and administration (2.3), use in specific populations (8.6), clinical pharmacology (12.3)]. consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (sr) in patients with renal impairment (gfr less than 90 ml/min). bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see dosage and administration (2.3), clinical pharmacology (12.3)] . in patients with moderate to severe hepatic impairment (child-pugh score: 7 to 15), the maximum dose of bupropion hydrochloride extended-release tablets (sr) is 100 mg/day or 150 mg every other day. in patients with mild hepatic impairment (child-pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [ see dosage and administration (2.2), clinical pharmacology (12.3)] . bupropion is not a controlled substance. humans controlled clinical trials conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed subjects showed some increase in motor activity and agitation/excitement, often typical of central stimulant activity. in a population of individuals experienced with drugs of abuse, a single oral dose of 400 mg of bupropion produced mild amphetamine-like activity as compared with placebo on the morphine-benzedrine subscale of the addiction research center inventories (arci) and a score greater than placebo but less than 15 mg of the schedule ii stimulant dextroamphetamine on the liking scale of the arci. these scales measure general feelings of euphoria and drug liking which are often associated with abuse potential. findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. nonetheless, evidence from single-dose trials does suggest that the recommended daily dosage of bupropion when administered orally in divided doses is not likely to be significantly reinforcing to amphetamine or cns stimulant abusers. however, higher doses (which could not be tested because of the risk of seizure) might be modestly attractive to those who abuse cns stimulant drugs. bupropion hydrochloride extended-release tablets (sr) are intended for oral use only. the inhalation of crushed tablets or injection of dissolved bupropion has been reported. seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection. animals studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. in rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavior response, and increase rates of responding in several schedule-controlled behavior paradigms. in primate models assessing the positive-reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. in rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram is indicated for the treatment of: additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets and lexapro (escitalopram) oral solution. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. escitalopram tablets are contraindicated in patients: risk summary based on data from published observational studies, exposure to ssris, 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 (5.7) and clinical considerations]. available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage. there are risks of persistent pulmonary hypertension of the newborn (pphn) (see data) and poor neonatal adaptation (see clinical considerations) with exposure to selective serotonin reuptake inhibitors (ssris), including escitalopram, during pregnancy. there are risks associated with untreated depression in pregnancy (see clinical considerations). in animal reproduction studies, both escitalopram and racemic citalopram have been shown to have adverse effects on embryo/fetal and postnatal development, including fetal structural abnormalities, when administered at doses greater than human therapeutic doses (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 the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal risk and/or embryo/fetal risk women who discontinue antidepressants are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective longitudinal study of 201 pregnant women with a history of major depression, who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of escitalopram in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.7)] . fetal/neonatal adverse reactions neonates exposed to ssris or snris, including escitalopram, late in 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)] . data human data exposure to ssris, particularly later in pregnancy, may increase the risk for pphn. pphn occurs in 1-2 per 1000 live births in the general populations and is associated with substantial neonatal morbidity and mortality. animal data in a rat embryo/fetal development study, oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses [approximately ≥ 55 times the maximum recommended human dose (mrhd) of 20 mg/day on a mg/m2 basis]. maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was present at all dose levels. the developmental no-effect dose of 56 mg/kg/day is approximately 27 times the mrhd of 20 mg on a mg/m2 basis. no malformations were observed at any of the doses tested (as high as 73 times the mrhd on a mg/m2 basis). when female rats were treated with escitalopram (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and growth retardation were noted at 48 mg/kg/day which is approximately 23 times the mrhd of 20 mg on a mg/m2 basis. slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) was seen at this dose. slightly increased offspring mortality was also seen at 24 mg/kg/day. the no-effect dose was 12 mg/kg/day which is approximately 6 times the mrhd of 20 mg on a mg/m2 basis. in two rat embryo/fetal development studies, oral administration of racemic citalopram (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose, which is approximately 18 times the mrhd of 60 mg/day on a mg/m2 basis. this dose was also associated with maternal toxicity (clinical signs, decreased body weight gain). the developmental no-effect dose was 56 mg/kg/day is approximately 9 times the mrhd on a mg/m2 basis. in a rabbit study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day, or approximately 5 times the mrhd on a mg/m2 basis. thus, developmental effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit. when female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were observed at the highest dose, which is approximately 5 times the mrhd of 60 mg on a mg/m2 basis. the no-effect dose was 12.8 mg/kg/day is approximately 2 times the mrhd on a mg/m 2 basis. similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, approximately 4 times the mrhd on a mg/m2 basis. a no-effect dose was not determined in that study. risk summary data from the published literature report the presence of escitalopram and desmethylescitalopram in human milk (see data ). there are reports of excessive sedation, restlessness, agitation, poor feeding and poor weight gain in infants exposed to escitalopram, through breast milk (see clinical considerations ). there are no data on the effects of escitalopram or its metabolites on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for escitalopram and any potential adverse effects on the breastfed child from escitalopram or from the underlying maternal condition. clinical considerations infants exposed to escitalopram should be monitored for excess sedation, restlessness, agitation, poor feeding and poor weight gain. data a study of 8 nursing mothers on escitalopram with daily doses of 10-20 mg/day showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram. major depressive disorder the safety and effectiveness of escitalopram for the treatment of major depressive disorder have been established in pediatric patients 12 years of age and older. use of escitalopram for this indication is supported by evidence from adequate and well-controlled studies in adults with additional evidence from an 8-week, flexible-dose, placebo-controlled study that compared escitalopram 10 mg to 20 mg once daily to placebo in pediatric patients 12 to 17 years of age with major depressive disorder [see clinical studies (14.1)] . the safety of escitalopram was similar to adult patients with mdd [see adverse reactions (6.1)] . the safety and effectiveness of escitalopram for the treatment of major depressive disorder have not been established in pediatric patients younger than 12 years of age. in a 24-week, open- label safety study in 118 pediatric patients aged 7 to 11 years who had major depressive disorder, the safety findings were consistent with the known safety and tolerability profile for escitalopram. generalized anxiety disorder the safety and effectiveness of escitalopram for the treatment of generalized anxiety disorder have not been established in pediatric patients younger than 7 years of age. antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see warnings and precautions (5.1)] . decreased appetite and weight loss have been observed in association with the use of ssris. consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an ssri such as escitalopram. juvenile animal toxicity data in a juvenile animal study, male and female rats were administered escitalopram at 5, 40, or 80 mg/kg/day by oral gavage from postnatal day (pnd) 21 to pnd 69. a delay in sexual maturation was observed in both males and females at ≥ 40 mg/kg/day with a no observed adverse effect level (noael) of 5 mg/kg/day. this noael was associated with plasma auc levels less than those measured at the maximum recommended dose (mrhd) in pediatrics (20 mg). however, there was no effect on reproductive function. increased motor activity (both ambulatory and fine movements) was observed in females prior to daily dosing at ≥ 40 mg/kg/day (3.5 times the mrhd based on auc levels). a reversible disruption of learning and memory function was observed in males at 80 mg/kg/day with a noael of 40 mg/kg/day, which was associated with an auc level 3.5 times those measured at the mrhd in pediatrics. there was no effect on learning and memory function in treated female rats. additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets and lexapro (escitalopram) oral solution. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. approximately 69 patients (6%) of the 1,144 patients receiving escitalopram in controlled trials of escitalopram in major depressive disorder and gad were 60 years of age or older [see clinical studies (14.1, 14.2)] . the number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram cannot be ruled out. in two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in subjects 65 years and older as compared to young subjects and cmax was unchanged [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram for elderly patients is 10 mg daily [see dosage and administration (2.5)] . ssris, including escitalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [ see warnings and precautions (5.6)] . of 4,422 patients in clinical studies of racemic citalopram, 1,357 were 60 and over, 1,034 were 65 and over, and 457 were 75 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the geriatric and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out. increased citalopram exposure occurs in patients with hepatic impairment [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram in patients with hepatic impairment is 10 mg daily [see dosage and administration (2.5)] . pharmacokinetics of escitalopram in patients with a creatinine clearance less than 20 ml/minute has not been evaluated. no dosage adjustment is necessary for patients with mild or moderate renal impairment [see dosage and administration (2.5), clinical pharmacology (12.3)] . physical and psychological dependence animal studies suggest that the abuse liability of racemic citalopram is low. escitalopram has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with escitalopram did not reveal any drug-seeking behavior. however, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate escitalopram patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1) - diclofenac sodium ophthalmic solution is indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction and for the temporary relief of pain and photophobia in patients undergoing corneal refractive surgery. diclofenac sodium ophthalmic solution is contraindicated in patients who are hypersensitive to any component of the medication.

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - citalopram hydrobromide (unii: i1e9d14f36) (citalopram - unii:0dhu5b8d6v) - citalopram tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies (14)] . citalopram tablets are contraindicated in patients: - taking, or within 14 days of stopping, maois (including maois such as linezolid or intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions (5.3), drug interactions (7)] . - taking pimozide because of risk of qt prolongation [see drug interactions (7)] . - with known hypersensitivity to citalopram or any of the inactive ingredients in citalopram tablets. reactions have included angioedema and anaphylaxis [see adverse reactions (6.2)]. 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 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants . risk summary based on data from published observational studies, exposure to ssris, 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]. available data from published epidemiologic studies and postmarketing reports with citalopram use in pregnancy have not established an increased risk of major birth defects or miscarriage. published studies demonstrated that citalopram levels in both cord blood and amniotic fluid are similar to those observed in maternal serum. there are risks of persistent pulmonary hypertension of the newborn (pphn) (see data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (ssris), including citalopram, during pregnancy. there also are risks associated with untreated depression in pregnancy (see clinical considerations) .   in animal reproduction studies, citalopram caused adverse embryo/fetal effects at doses that caused maternal toxicity (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 the clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.   clinical considerations disease-associated maternal and/or embryo/fetal risk women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of citalopram 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 neonates exposed to citalopram and other ssris late in 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 findings are consistent with either a direct toxic effect of ssris 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 (5.3)] . data human data exposure during late pregnancy to ssris may have an increased risk for persistent pulmonary hypertension of the newborn (pphn). pphn occurs in 1 to 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. animal data citalopram was administered orally to pregnant rats during the period of organogenesis at doses of 32, 56, and 112 mg/kg/day, which are approximately 8, 14, and 27 times the maximum recommended human dose (mrhd) of 40 mg, based on mg/m2   body surface area. citalopram caused maternal toxicity of cns clinical signs and decreased weight gain at 112 mg/kg/day, which is 27 times the mrhd. at this maternally toxic dose, citalopram decreased embryo/fetal growth and survival and increased fetal abnormalities (including cardiovascular and skeletal defects). the no observed adverse effect level (noael) for maternal and embryofetal toxicity is 56 mg/kg/day, which is approximately 14 times the mrhd. citalopram was administered orally to pregnant rabbits during the period of organogenesis at doses up to 16 mg/kg/day, which is approximately 8 times the mrhd of 40 mg, based on mg/m2 body surface area. no maternal or embryofetal toxicity was observed. the noael for maternal and embryofetal toxicity is 16 mg/kg/day, which is approximately 8 times the mrhd. citalopram was administered orally to pregnant rats during late gestation and lactation periods at doses of 4.8, 12.8, and 32 mg/kg/day, which are approximately 1, 3, and 8 times the mrhd of 40 mg, based on mg/m2 body surface area. citalopram increased offspring mortality during the first 4 days of birth and decreased offspring growth at 32 mg/kg/day, which is approximately 8 times the mrhd. the noael for developmental toxicity is 12.8 mg/kg/day, which is approximately 3 times the mrhd. in a separate study, similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, which is approximately 6 times the mrhd. a noael was not determined in that study. risk summary data from the published literature report the presence of citalopram in human milk at relative infant doses ranging between 0.7 to 9.4% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.78 to 4.3. there are reports of breastfed infants exposed to citalopram experiencing irritability, restlessness, excessive somnolence, decreased feeding, and weight loss (see clinical considerations). there is no information about effects of citalopram on milk production.   the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for citalopram and any potential adverse effects on the breastfed child from citalopram or from the underlying maternal condition.   clinical considerations monitor breastfeeding infants for adverse reactions, such as irritability, restlessness, excessive somnolence, decreased feeding, and weight loss. the safety and effectiveness of citalopram have not been established in pediatric patients. two placebo-controlled trials in 407 pediatric patients with mdd have been conducted with citalopram, and the data were not sufficient to support use in pediatric patients.   antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see boxed warning, warnings and precautions (5.1)] . decreased appetite and weight loss have been observed in association with the use of ssris in pediatric patients. of 4422 patients in clinical studies of citalopram, 1357 were 60 and over, 1034 were 65 and over, and 457 were 75 and over. in two pharmacokinetic studies, citalopram auc was increased by 23% and 30%, respectively, in subjects ≥ 60 years of age as compared to younger subjects, and its half-life was increased by 30% and 50%, respectively [see clinical pharmacology (12.3)] . therefore, the maximum recommended dosage in patients 60 years of age and older is lower than younger patients [see dosage and administration (2.3), warnings and precautions (5.2)] .   ssris, including citalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.9)] . increased citalopram exposure occurs in patients with hepatic impairment. the maximum recommended dosage of citalopram is lower in patients with hepatic impairment [see dosage and administration (2.3), clinical pharmacology (12.3)]. citalopram hydrobromide is not a controlled substance. animal studies suggest that the abuse liability of citalopram is low. citalopram has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with citalopram did not reveal any drug-seeking behavior. however, these observations were not systematic and it is not possible to predict, on the basis of this limited experience, the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed. consequently, health care providers should carefully evaluate citalopram patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - empagliflozin (unii: hdc1r2m35u) (empagliflozin - unii:hdc1r2m35u) - jardiance is indicated: - to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. - to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. - as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use jardiance is not recommended in patients with type 1 diabetes mellitus. it may increase the risk of diabetic ketoacidosis in these patients [see warnings and precautions (5.1)] . jardiance is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an egfr less than 30 ml/min/1.73 m2 . jardiance is likely to be ineffective in this setting based upon its mechanism of action. - hypersensitivity to empagliflozin or any of the excipients in jardiance, reactions such as angioedema have occurred [see warnings and precautions (5.7)] . - patients on dialysis [see use in specific population

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - dulaglutide (unii: wtt295hsy5) (dulaglutide - unii:wtt295hsy5) - trulicity® is indicated: - as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors. limitations of use trulicity: - has not been studied in patients with a history of pancreatitis [see warnings and precautions (5.2)] . consider other antidiabetic therapies in patients with a history of pancreatitis. - should not be used in patients with type 1 diabetes mellitus. - has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and is therefore not recommended in these patients [see warnings and precautions (5.6)] . trulicity is contraindicated in patients with: - personal or family history of medullary thyroid carcino

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - dulaglutide (unii: wtt295hsy5) (dulaglutide - unii:wtt295hsy5) - trulicity® is indicated: - as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors. limitations of use trulicity: - has not been studied in patients with a history of pancreatitis [see warnings and precautions (5.2)] . consider other antidiabetic therapies in patients with a history of pancreatitis. - should not be used in patients with type 1 diabetes mellitus. - has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and is therefore not recommended in these patients [see warnings and precautions (5.6)] . trulicity is contraindicated in patients with: - personal or family history of medullary thyroid carcino

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - empagliflozin (unii: hdc1r2m35u) (empagliflozin - unii:hdc1r2m35u) - jardiance is indicated: - to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. - to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. - as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use jardiance is not recommended in patients with type 1 diabetes mellitus. it may increase the risk of diabetic ketoacidosis in these patients [see warnings and precautions (5.1)] . jardiance is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an egfr less than 30 ml/min/1.73 m2 . jardiance is likely to be ineffective in this setting based upon its mechanism of action. - hypersensitivity to empagliflozin or any of the excipients in jardiance, reactions such as angioedema have occurred [see warnings and precautions (5.7)] . - patients on dialysis [see use in specific population

Bandaríkin - enska - NLM (National Library of Medicine)

a-s medication solutions - triazolam (unii: 1hm943223r) (triazolam - unii:1hm943223r) - triazolam is indicated for the short-term treatment of insomnia (generally 7 to 10 days) in adults. triazolam is contraindicated in: - patients with known hypersensitivity to triazolam, any of component of triazolam tablets, or other benzodiazepines. reactions consistent with angioedema (involving the tongue, glottis, or larynx), dyspnea, and throat closing have been reported and may be fatal. - concomitant administration of strong cytochrome p450 (cyp 3a) enzyme inhibitors (e.g., ketoconazole, itraconazole, nefazodone, lopinavir, ritonavir) [ see warnings and precautions (5.8), drug interactions (7.1) ] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to triazolam during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for other psychiatric medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermed