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pd-rx pharmaceuticals, inc. - citalopram hydrobromide (unii: i1e9d14f36) (citalopram - unii:0dhu5b8d6v) - citalopram tablets are indicated for the treatment of depression. the efficacy of citalopram tablets in the treatment of depression was established in 4 to 6 week, controlled trials of outpatients whose diagnosis corresponded most closely to the dsm-iii and dsm-iii-r category of major depressive disorder (see clinical pharmacology ). a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. the antidepressant action of citalopram tablets in hospitalized depressed patients has not been adequately studied. t

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

pd-rx pharmaceuticals, inc. - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate tablets are indicated as initial monotherapy for the treatment of partial-onset or primary generalized tonic-clonic seizures in patients 2 years of age and older. topiramate tablets are indicated as adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with lennox-gastaut syndrome in patients 2 years of age and older. topiramate tablets are indicated for the preventive treatment of migraine in patients 12 years of age and older. none. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to topiramate during pregnancy. patients should be encouraged to enroll in the north american antiepileptic drug (naaed) pregnancy registry if they become pregnant. this registry is collecting information about the safety of antiepileptic drugs during pregnancy. to enroll, patients can call the toll-free number 1-888-233-2334. information about the north american drug pregnancy registry can be found at http://www.aedpregnancyregistry.org/ . risk summary topiramate can cause fetal harm when administered to a pregnant woman. data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk of major congenital malformations, including but not limited to  cleft lip and/or cleft palate (oral clefts), and of being small for gestational age (sga) [see human data] . sga has been observed at all doses and appears to be dose-dependent. the prevalence of sga is greater in infants of women who received higher doses of topiramate during pregnancy. in addition, the prevalence of sga in infants of women who continued topiramate use until later in pregnancy is higher compared to the prevalence in infants of women who stopped topiramate use before the third trimester.     in multiple animal species, topiramate produced developmental toxicity, including increased incidences of fetal malformations, in the absence of maternal toxicity at clinically relevant doses [see animal data] . all pregnancies have a background risk of birth defects, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions consider the benefits and risks of topiramate when prescribing this drug to women of childbearing potential, particularly when topiramate is considered for a condition not usually associated with permanent injury or death. because of the risk of oral clefts to the fetus, which occur in the first trimester of pregnancy, all women of childbearing potential should be informed of the potential risk to the fetus from exposure to topiramate. women who are planning a pregnancy should be counseled regarding the relative risks and benefits of topiramate use during pregnancy, and alternative therapeutic options should be considered for these patients. labor or delivery although the effect of topiramate on labor and delivery in humans has not been established, the development of topiramate-induced metabolic acidosis in the mother and/or in the fetus might affect the fetus’ ability to tolerate labor. topiramate treatment can cause metabolic acidosis [see warnings and precautions (5.4)]. the effect of topiramate-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus’ ability to tolerate labor. pregnant patients should be monitored for metabolic acidosis and treated as in the nonpregnant state [see warnings and precautions (5.4)]. newborns of mothers treated with topiramate should be monitored for metabolic acidosis because of transfer of topiramate to the fetus and possible occurrence of transient metabolic acidosis following birth. based on limited information, topiramate has also been associated with pre-term labor and premature delivery. data human data data from pregnancy registries indicate an increased risk of major congenital malformations, including but not limited to oral clefts in infants exposed to topiramate during the first trimester of pregnancy. other than oral clefts, no specific pattern of major congenital malformations or grouping of major congenital malformation types were observed. in the naaed pregnancy registry, when topiramate-exposed infants with only oral clefts were excluded, the prevalence of major congenital malformations (4.1%) was higher than that in infants exposed to a reference aed (1.8%) or in infants with mothers without epilepsy and without exposure to aeds (1.1%). the prevalence of oral clefts among topiramate-exposed infants  (1.4%) was higher than the prevalence  in infants exposed to a reference aed (0.3%) or the prevalence in infants with mothers without epilepsy and without exposure to aeds(0.11%). it was also higher than the background prevalence in united states (0.17%) as estimated by the centers for disease control and prevention (cdc). the relative risk of oral clefts in topiramate-exposed pregnancies in the naaed pregnancy registry was 12.5 (95% confidence interval [ci]5.9 to 26.37) as compared to the risk in a background population of untreated women. the uk epilepsy and pregnancy register reported a prevalence of oral clefts among infants exposed to topiramate monotherapy (3.2%) that was 16 times higher than the background rate in the uk (0.2%). data from the naaed pregnancy registry and a population-based birth registry cohort indicate that exposure to topiramate in utero is associated with an increased risk of sga newborns (birth weight <10th percentile). in the naaed pregnancy registry, 19.7% of topiramate-exposed newborns were sga compared to 7.9% of newborns exposed to a reference aed and 5.4% of newborns of mothers without epilepsy and without aed exposure. in the medical birth registry of norway (mbrn), a population-based pregnancy registry, 25% of newborns in the topiramate monotherapy exposure group were sga compared to 9 % in the comparison group unexposed to aeds. the long-term consequences of the sga findings are not known. animal data when topiramate (0, 20, 100, or 500 mg/kg/day) was administered to pregnant mice during the period of organogenesis, incidences of fetal malformations (primarily craniofacial defects) were increased at all doses. fetal body weights and skeletal ossification were reduced at the highest dose tested in conjunction with decreased maternal body weight gain. a no-effect dose for embryofetal developmental toxicity in mice was not identified. the lowest dose tested, which was associated with increased malformations, is less than the maximum recommended human dose (mrhd) for epilepsy (400 mg/day) or migraine (100 mg/day) on a body surface area (mg/m 2 ) basis. in pregnant rats administered topiramate (0, 20, 100, and 500 mg/kg/day or 0, 0.2, 2.5, 30, and 400 mg/kg/day) orally during the period of organogenesis, the frequency of limb malformations (ectrodactyly, micromelia, and amelia) was increased in fetuses at 400 and 500 mg/kg/day. embryotoxicity (reduced fetal body weights, increased incidences of structural variations) was observed at doses as low as 20 mg/kg/day. clinical signs of maternal toxicity were seen at 400 mg/kg/day and above, and maternal body weight gain was reduced at doses of 100 mg/kg/day or greater. the no-effect dose (2.5 mg/kg/day) for embryofetal developmental toxicity in rats is less than the mrhd for epilepsy or migraine on a mg/m 2 basis. in pregnant rabbits administered topiramate (0, 20, 60, and 180 mg/kg/day or 0, 10, 35, and 120 mg/kg/day) orally during organogenesis, embryofetal mortality was increased at 35 mg/kg/day, and increased incidences of fetal malformations (primarily rib and vertebral malformations) were observed at 120 mg/kg/day. evidence of maternal toxicity (decreased body weight gain, clinical signs, and/or mortality) was seen at 35 mg/kg/day and above. the no-effect dose (20 mg/kg/day) for embryofetal developmental toxicity in rabbits is equivalent to the mrhd for epilepsy and approximately 4 times the mrhd for migraine on a mg/m 2 basis. when topiramate (0, 0.2, 4, 20, and 100 mg/kg/day or 0, 2, 20, and 200 mg/kg/day) was administered orally to female rats during the latter part of gestation and throughout lactation, offspring exhibited decreased viability and delayed physical development at 200 mg/kg/day and reductions in pre- and/or postweaning body weight gain at 2 mg/kg/day and above. maternal toxicity (decreased body weight gain, clinical signs) was evident at 100 mg/kg/day or greater. in a rat embryofetal development study which included postnatal assessment of offspring, oral administration of topiramate (0, 0.2, 2.5, 30, and 400 mg/kg) to pregnant animals during the period of organogenesis resulted in delayed physical development in offspring at 400 mg/kg/day and persistent reductions in body weight gain in offspring at 30 mg/kg/day and higher. the no-effect dose (0.2 mg/kg/day) for pre- and postnatal developmental toxicity in rats is less than the mrhd for epilepsy or migraine on a mg/m 2 basis. risk summary topiramate is excreted in human milk [see data]. the effects of topiramate on milk production are unknown. diarrhea and somnolence have been reported in breastfed infants whose mothers receive topiramate treatment. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for topiramate and any potential adverse effects on the breastfed infant from topiramate or from the underlying maternal condition. data human data limited data from 5 women with epilepsy treated with topiramate during lactation showed drug levels in milk similar to those in maternal plasma. contraception women of childbearing potential who are not planning a pregnancy should use effective contraception because of the risk of major congenital malformations, including oral clefts, and the risk of infants being  sga [see drug interactions (7.4) and use in specific populations 8.1] . adjunctive treatment for epilepsy pediatric patients 2 years of age and older the safety and effectiveness of topiramate as adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with lennox-gastaut syndrome have been established in pediatric patients 2 years of age and older [see adverse reactions (6.1) and clinical studies (14.2)] . pediatric patients below the age of 2 years safety and effectiveness in patients below the age of 2 years have not been established for the adjunctive therapy treatment of partial-onset seizures, primary generalized tonic-clonic seizures, or seizures associated with lennox-gastaut syndrome. in a single randomized, double-blind, placebo-controlled investigational trial, the efficacy, safety, and tolerability of topiramate oral liquid and sprinkle formulations as an adjunct to concurrent antiepileptic drug therapy in pediatric patients 1 to 24 months of age with refractory partial-onset seizures were assessed. after 20 days of double-blind treatment, topiramate (at fixed doses of 5, 15, and 25 mg/kg/day) did not demonstrate efficacy compared with placebo in controlling seizures. in general, the adverse reaction profile for topiramate in this population was similar to that of older pediatric patients, although results from the above controlled study and an open-label, long-term extension study in these pediatric patients 1 to 24 months old suggested some adverse reactions/toxicities (not previously observed in older pediatric patients and adults; i.e., growth/length retardation, certain clinical laboratory abnormalities, and other adverse reactions/toxicities that occurred with a greater frequency and/or greater severity than had been recognized previously from studies in older pediatric patients or adults for various indications). these very young pediatric patients appeared to experience an increased risk for infections (any topiramate dose 12%, placebo 0%) and  of  respiratory   disorders   (any   topiramate dose 40%, placebo 16%). the following adverse reactions were observed in at least 3% of patients on topiramate and were 3% to 7% more frequent than in patients on placebo: viral infection, bronchitis, pharyngitis, rhinitis, otitis media, upper respiratory infection, cough, and bronchospasm. a generally similar profile was observed in older pediatric patients [see adverse reactions (6)]. topiramate resulted in an increased incidence of patients with increased creatinine (any topiramate dose 5%, placebo 0%), bun (any topiramate dose 3%, placebo 0%), and protein (any topiramate dose 34%, placebo 6%), and an increased incidence of decreased potassium (any topiramate dose 7%, placebo 0%). this increased frequency of abnormal values was not dose-related. creatinine was the only analyte showing a noteworthy increased incidence (topiramate 25 mg/kg/day 5%, placebo 0%) of a markedly abnormal increase. the significance of these findings is uncertain. topiramate treatment also produced a dose-related increase in the percentage of patients who had a shift from normal at baseline to high/increased (above the normal reference range) in total eosinophil count at the end of treatment. the incidence of these abnormal shifts was 6 % for placebo, 10% for 5 mg/kg/day, 9% for 15 mg/kg/day, 14% for 25 mg/kg/day, and 11% for any topiramate dose. there was a mean dose-related increase in alkaline phosphatase. the significance of these findings is uncertain. topiramate produced a dose-related increased incidence of hyperammonemia [see warnings and precautions (5.12)]. treatment with topiramate for up to 1 year was associated with reductions in z scores for length, weight, and head circumference [see warnings and precautions (5.4), adverse reactions (6)]. in open-label, uncontrolled experience, increasing impairment of adaptive behavior was documented in behavioral testing over time in this population. there was a suggestion that this effect was dose-related. however, because of the absence of an appropriate control group, it is not known if this decrement in function was treatment-related or reflects the patient’s underlying disease (e.g., patients who received higher doses may have more severe underlying disease) [see warnings and precautions (5.6) ]. in this open-label, uncontrolled study, the mortality was 37 deaths/1000 patient years. it is not possible to know whether this mortality rate is related to topiramate treatment, because the background mortality rate for a similar, significantly refractory, young pediatric population (1 to 24 months) with partial epilepsy is not known. monotherapy treatment for epilepsy pediatric patients 2 years of age and older   the safety and effectiveness of topiramate as monotherapy for the treatment of  partial-onset seizures or primary generalized tonic-clonic seizures have been established in pediatric patients aged 2 years and older [see adverse reactions (6.1), clinical studies (14.1)] .   a one-year, active-controlled, open-label study with blinded assessments of bone mineral density (bmd) and growth in pediatric patients 4 to 15 years of age, including 63 patients with recent or new onset of epilepsy, was conducted to assess effects of topiramate (n=28, 6 to 15 years of age) versus levetiracetam (n=35, 4 to 15 years of age) monotherapy on bone mineralization and on height and weight, which reflect growth. effects on bone mineralization were evaluated via dual-energy x-ray absorptiometry and blood markers. table 10 summarizes effects of topiramate at 12 months for key safety outcomes including bmd, height, height velocity, and weight. all least square mean values for topiramate   and the comparator were positive. therefore, the least square mean treatment differences shown reflect a topiramate -induced attenuation of the key safety outcomes. statistically significant effects were observed for decreases in bmd (and bone mineral content) in lumbar spine and total body less head and in weight. subgroup analyses according to age demonstrated similar negative effects for all key safety outcomes (i.e., bmd, height, weight).   table 10 summary of topiramate treatment difference results at 12 months for key safety outcomes metabolic acidosis (serum bicarbonate < 20 meq/l) was observed in all topiramate-treated patients at some time in the study [see warnings and precautions (5.4)] . over the whole study, 76% more topiramate-treated patients experienced persistent metabolic acidosis (i.e. 2 consecutive visits with or final serum bicarbonate < 20 meq/l) compared to levetiracetam treated patients. over the whole study, 35% more topiramate-treated patients experienced a markedly abnormally low serum bicarbonate (i.e., absolute value < 17 meq/l and ≥ 5 meq/l decrease from pre-treatment), indicating the frequency of more severe metabolic acidosis, compared to levetiracetam-treated patients. the decrease in bmd at 12 months was correlated with decreased serum bicarbonate, suggesting that metabolic acidosis was at least a partial factor contributing to this adverse effect on bmd. topiramate-treated patients exhibited an increased risk for developing an increased serum creatinine and an increased serum glucose above the normal reference range compared to control patients. pediatric patients below the age of 2 years safety and effectiveness in patients below the age of 2 years have not been established for the monotherapy treatment of epilepsy. preventive treatment of migraine  pediatric patients 12 to 17 years of age safety and  effectiveness  of  topiramate  for the preventive treatment of migraine was studied in 5 double-blind, randomized, placebo-controlled, parallel-group trials in a total of 219 pediatric patients, at doses of 50 to 200 mg/day, or 2 to 3 mg/kg/day. these comprised a fixed dose study in 103 pediatric patients 12 to 17 years of age [see clinical studies (14.3) ], a flexible dose (2 to 3 mg/kg/day), placebo-controlled study in 157 pediatric patients 6 to 16 years of age (including 67 pediatric patients 12 to 16 years of age), and a total of 49 pediatric patients 12 to 17 years of age in 3 studies for the preventive treatment of migraine primarily in adults. open-label extension phases of 3 studies enabled evaluation of long-term safety for up to 6 months after the end of the double-blind phase. efficacy of topiramate for the preventive treatment of migraine in pediatric patients 12 to 17 years of age is demonstrated for a 100 mg daily dose in study 13  [see clinical studies (14.3)] . efficacy of topiramate (2 to 3 mg/kg/day) for the preventive treatment of migraine was not demonstrated in a placebo- controlled trial of 157 pediatric  patients  (6  to  16 years  of  age)  that  included  treatment  of 67 pediatric patients (12 to 16 years of age) for 20 weeks. in the pediatric trials (12 to 17 years of age) in which patients were randomized to placebo or a fixed daily dose of topiramate, the most common adverse reactions with topiramate that were seen at an incidence higher (≥5%) than in the placebo group were: paresthesia, upper respiratory tract infection, anorexia, and abdominal pain [see adverse reactions (6) ]. the most common cognitive adverse reaction in pooled double-blind studies in pediatric patients 12 to 17 years of age was difficulty with concentration/attention [see warnings and precautions (5.6) ]. markedly abnormally low serum bicarbonate values indicative of metabolic acidosis were reported in topiramate-treated pediatric migraine patients [see warnings and precautions (5.4) ]. in topiramate-treated pediatric patients (12 to 17 years of age) compared to placebo-treated patients, abnormally increased results were more frequent for creatinine, bun, uric acid, chloride, ammonia, total protein, and platelets. abnormally decreased results were observed with topiramate vs placebo treatment for phosphorus and bicarbonate [see adverse reactions   (6.1)]. notable changes (increases and decreases) from baseline in systolic blood pressure, diastolic blood pressure, and pulse were observed occurred more commonly in pediatric patients treated with topiramate compared to pediatric patients treated with placebo [see clinical pharmacology (12.2)] . pediatric patients  below the age of 12 years safety and effectiveness in pediatric patients below the age of 12 years have not been established for the preventive treatment of migraine. in  a  double-blind  study   in   90 pediatric   patients   6   to   11 years   of   age   (including 59 topiramate-treated and 31 placebo patients), the adverse reaction profile was generally similar to that seen in pooled double-blind studies of pediatric patients 12 to 17 years of age. the most common adverse reactions that occurred in topiramate-treated pediatric patients 6 to 11 years of age, and at least twice as frequently than placebo, were gastroenteritis (12% topiramate, 6% placebo), sinusitis (10% topiramate, 3% placebo), weight loss (8% topiramate, 3% placebo) and paresthesia (7% topiramate,  0% placebo).  difficulty with  concentration/attention  occurred  in 3 topiramate-treated patients (5%) and 0 placebo-treated patients. the risk for cognitive adverse reaction was greater in younger patients (6 to 11 years of age) than in older patients (12 to 17 years of age) [see warnings and precautions (5.6)]. juvenile animal studies when topiramate (0, 30, 90, and 300 mg/kg/day) was administered orally to rats during the juvenile period of development (postnatal days 12 to 50), bone growth plate thickness was reduced in males at the highest dose. the no-effect dose (90 mg/kg/day) for adverse developmental effects is approximately 2 times the maximum recommended pediatric dose (9 mg/kg/day) on a body surface area (mg/m 2 ) basis. in clinical trials, 3% of patients were over age 60. no age-related differences in effectiveness or adverse effects were evident. however, clinical studies of topiramate did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently than younger subjects. dosage adjustment may be necessary for elderly with age-related renal impairment (creatinine clearance rate <70 ml/min/1.73 m 2 ) resulting in reduced clearance [see dosage and administration (2.5), clinical pharmacology (12.3)]. the clearance of topiramate is reduced in patients with moderate (creatinine clearance 30 to 69 ml/min/1.73 m 2 ) and severe (creatinine clearance <30 ml/min/1.73 m 2 ) renal impairment. a dosage adjustment is recommended in patients with moderate or severe renal impairment [see dosage and administration (2.5), clinical pharmacology (12.3)]. topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than in a normal individual. a dosage adjustment may be required [see dosage and administration (2.6), clinical pharmacology (12.3)].

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

pd-rx pharmaceuticals, inc. - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram tablet is 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 and lexapro (escitalopram) oral solution. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. escitalopram tablet is 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/clnical-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 oxalate, 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 oxalate 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 oxalate, 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 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/m 2 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/m 2 basis. no malformations were observed at any of the doses tested (as high as 73 times the mrhd on a mg/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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 oxalate and any potential adverse effects on the breastfed child from escitalopram oxalate or from the underlying maternal condition. clinical considerations infants exposed to escitalopram oxalate 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 oxalate for the treatment of major depressive disorder have been established in pediatric patients 12 years of age and older. use of escitalopram oxalate 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 oxalate 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 oxalate was similar to adult patients with mdd [see adverse reactions ( 6.1)]. the safety and effectiveness of escitalopram oxalate 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 oxalate. generalized anxiety disorder the safety and effectiveness of escitalopram oxalate 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 oxalate. 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 oxalate 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 oxalate 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 oxalate for elderly patients is 10 mg daily [see dosage and administration ( 2.5)]. ssris, including escitalopram oxalate, 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 oxalate in patients with hepatic impairment is 10 mg daily [see dosage and administration ( 2.5)]. pharmacokinetics of escitalopram oxalate 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 oxalate has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with escitalopram oxalate 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 oxalate 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).

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pd-rx pharmaceuticals, inc. - 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) inadults. 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 is 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/clnical-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 oxalate, 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 oxalate 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 oxalate, 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 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/m 2 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/m 2 basis. no malformations were observed at any of the doses tested (as high as 73 times the mrhd on a mg/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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/m 2 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 oxalate and any potential adverse effects on the breastfed child from escitalopram oxalate or from the underlying maternal condition. clinical considerations infants exposed to escitalopram oxalate 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 oxalate for the treatment of major depressive disorder have been established in pediatric patients 12 years of age and older. use of escitalopram oxalate 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 oxalate 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 oxalate was similar to adult patients with mdd [see adverse reactions (6.1)] . the safety and effectiveness of escitalopram oxalate 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 oxalate. generalized anxiety disorder the safety and effectiveness of escitalopram oxalate 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 oxalate. 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 oxalate 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 oxalate 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 c max was unchanged [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram oxalate for elderly patients is 10 mg daily [see dosage and administration (2.5)] . ssris, including escitalopram oxalate, 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 oxalate in patients with hepatic impairment is 10 mg daily [see dosage and administration (2.5)] . pharmacokinetics of escitalopram oxalate 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 oxalate has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with escitalopram oxalate 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 oxalate 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).

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pd-rx pharmaceuticals, inc. - lorazepam (unii: o26fzp769l) (lorazepam - unii:o26fzp769l) - lorazepam tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. the effectiveness of lorazepam in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. the physician should periodically reassess the usefulness of the drug for the individual patient. lorazepam is contraindicated in patients with: - hypersensitivity to benzodiazepines or to any components of the formulation - acute narrow-angle glaucoma. controlled substance lorazepam tablets contain lorazepam, a schedule iv controlled substance. abuse lorazepam tablets are a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings: abuse, misuse, and addiction). the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). dependence physical dependence lorazepam tablets may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use (see warnings: dependence and withdrawal reactions) . to reduce the risk of withdrawal reactions, use a gradual taper to discontinue lorazepam tablets or reduce the dosage (see dosage and administration: discontinuation or dosage reduction of lorazepam tablets and warnings) . acute withdrawal signs and symptoms acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures and suicidality. protracted withdrawal syndrome protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance tolerance to lorazepam tablets may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of lorazepam tablets may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

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pd-rx pharmaceuticals, inc. - quetiapine fumarate (unii: 2s3pl1b6uj) (quetiapine - unii:bgl0jsy5si) - quetiapine is indicated for the treatment of schizophrenia. the efficacy of quetiapine in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents (13 to 17 years). the effectiveness of quetiapine for the maintenance treatment of schizophrenia has not been systematically evaluated in controlled clinical trials [ see clinical studies (14.1) ]. quetiapine is indicated for the acute treatment of manic episodes associated with bipolar i disorder, both as monotherapy and as an adjunct to lithium or divalproex. efficacy was established in two 12-week monotherapy trials in adults, in one 3-week adjunctive trial in adults, and in one 3-week monotherapy trial in pediatric patients (10 to 17 years) [ see clinical studies (14.2) ]. quetiapine is indicated as monotherapy for the acute treatment of depressive episodes associated with bipolar disorder. efficacy was established in two 8-week monotherapy trials in adult patients with bipolar i and bipolar ii disorder [ see clinical studies (14.2) ]. quetiapine is indicated for the maintenance treatment of bipolar i disorder, as an adjunct to lithium or divalproex. efficacy was established in two maintenance trials in adults. the effectiveness of quetiapine as monotherapy for the maintenance treatment of bipolar disorder has not been systematically evaluated in controlled clinical trials [ see clinical studies (14.2) ]. pediatric schizophrenia and bipolar i disorder are serious mental disorders, however, diagnosis can be challenging. for pediatric schizophrenia, symptom profiles can be variable, and for bipolar i disorder, patients may have variable patterns of periodicity of manic or mixed symptoms. it is recommended that medication therapy for pediatric schizophrenia and bipolar i disorder be initiated only after a thorough diagnostic evaluation has been performed and careful consideration given to the risks associated with medication treatment. medication treatment for both pediatric schizophrenia and bipolar i disorder is indicated as part of a total treatment program that often includes psychological, educational and social interventions. hypersensitivity to quetiapine or to any excipients in the quetiapine formulation. anaphylactic reactions have been reported in patients treated with quetiapine. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including quetiapine tablets, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ .   risk summary neonates exposed to antipsychotic drugs ( including quetiapine tablet) during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see clinical considerations). overall available data from published epidemiologic studies of pregnant women exposed to quetiapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data). there are risks to the mother associated with untreated schizophrenia, bipolar i, or major depressive disorder, and with exposure to antipsychotics, including, quetiapine tablet during pregnancy (see clinical considerations) . in animal studies, embryo-fetal toxicity occurred including delays in skeletal ossification at approximately 1 and 2 times the maximum recommended human dose (mrhd) of 800 mg/day in both rats and rabbits, and an increased incidence of carpal/tarsal flexure (minor soft tissue anomaly) in rabbit fetuses at approximately 2 times the mrhd. in addition, fetal weights were decreased in both species. maternal toxicity (observed as decreased body weights and/or death) occurred at 2 times the mrhd in rats and approximately 1-2 times the mrhd in rabbits. the estimated background risk of major birth defects and miscarriage for the indicated populations 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 fetal risk   there is a risk to the mother from untreated schizophrenia, or bipolar i disorder, including increased risk of relapse, hospitalization, and suicide. schizophrenia and bipolar i disorder are associated with increased adverse perinatal outcomes, including preterm birth. it is not known if this is a direct result of the illness or other comorbid factors. a prospective, longitudinal study followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants 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 risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. fetal/neonatal adverse reactions   extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including quetiapine tablets, during the third trimester of pregnancy. these symptoms varied in severity. monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. data   human data   published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. a retrospective cohort study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk of major birth defects. animal data   when pregnant rats and rabbits were exposed to quetiapine during organogenesis, there was no teratogenic effect in fetuses. doses were 25, 50 and 200 mg/kg in rats and 25, 50 and 100 mg/kg in rabbits which are approximately 0.3, 0.6 and 2-times (rats) and 0.6, 1 and 2-times (rabbits) the mrhd, for schizophrenia of 800 mg/day based on mg/m 2 body surface area. however, there was evidence of embryo-fetal toxicity, including delays in skeletal ossification at approximately 1 and 2 times the mrhd of 800 mg/day in both rats and rabbits and an increased incidence of carpal/tarsal flexure (minor soft tissue anomaly) in rabbit fetuses at approximately 2 times the mrhd. in addition, fetal weights were decreased in both species. maternal toxicity (observed as decreased body weights and/or death) occurred at 2 times the mrhd in rats and at approximately 1-2 times the mrhd (all doses tested) in rabbits. in a peri/postnatal reproductive study in rats, no drug-related effects were observed when pregnant dams were treated with quetiapine at doses 0.01, 0.1, and 0.2 times the mrhd of 800 mg/day based on mg/m 2 body surface area. however, in a preliminary peri/postnatal study, there were increases in fetal and pup death, and decreases in mean litter weight at 3 times the mrhd. risk summary limited data from published literature report the presence of quetiapine in human breast milk at relative infant dose of <1% of the maternal weight-adjusted dosage. there are no consistent adverse events that have been reported in infants exposed to quetiapine through breast milk. there is no information on the effects of quetiapine on milk production. the developmental and health  benefits of breastfeeding should be considered along with the mother’s clinical need for quetiapine tablets and any potential adverse effects on the breastfed child from quetiapine tablets or from the mother’s underlying condition. infertility   females   based on the pharmacologic action of quetiapine (d2 antagonism), treatment with quetiapine tablets may result in an increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential [see warnings and precautions ( 5.15)]. in general, the adverse reactions observed in children and adolescents during the clinical trials were similar to those in the adult population with few exceptions.  increases in systolic and diastolic blood pressure occurred in children and adolescents and did not occur in adults.  orthostatic hypotension occurred more frequently in adults (4-7%) compared to children and adolescents (< 1%) [see warnings and precautions ( 5.7) and adverse reactions ( 6.1)]. schizophrenia the efficacy and safety of quetiapine in the treatment of schizophrenia in adolescents aged 13 to 17 years were demonstrated in one 6-week, double-blind, placebo-controlled trial [see indications and usage ( 1.1), dosage and administration ( 2.2), adverse reactions ( 6.1), and clinical studies ( 14.1)]. safety and effectiveness of quetiapine in pediatric patients less than 13 years of age with schizophrenia have not been established. maintenance the safety and effectiveness of quetiapine in the maintenance treatment of bipolar disorder has not been established in pediatric patients less than 18 years of age. the safety and effectiveness of quetiapine in the maintenance treatment of schizophrenia has not been established in any patient population, including pediatric patients. bipolar mania the efficacy and safety of quetiapine in the treatment of mania in children and adolescents ages 10 to 17 years with bipolar i disorder was demonstrated in a 3-week, double-blind, placebo-controlled, multicenter trial [see indications and usage ( 1.2), dosage and administration ( 2.3), adverse reactions ( 6.1), and clinical studies ( 14.2)] . safety and effectiveness of quetiapine in pediatric patients less than 10 years of age with bipolar mania have not been established. bipolar depression safety and effectiveness of quetiapine in pediatric patients less than 18 years of age with bipolar depression have not been established. a clinical trial with seroquel xr was conducted in children and adolescents (10 to 17 years of age) with bipolar depression, efficacy was not established. some differences in the pharmacokinetics of quetiapine were noted between children/adolescents (10 to 17 years of age) and adults.  when adjusted for weight, the auc and cmax of quetiapine were 41% and 39% lower, respectively, in children and adolescents compared to adults. the pharmacokinetics of the active metabolite, norquetiapine, were similar between children/adolescents and adults after adjusting for weight [see clinical pharmacology ( 12.3)] . of the approximately 3700 patients in clinical studies with quetiapine, 7% (232) were 65 years of age or over.  in general, there was no indication of any different tolerability of quetiapine in the elderly compared to younger adults. nevertheless, the presence of factors that might decrease pharmacokinetic clearance, increase the pharmacodynamic response to quetiapine, or cause poorer tolerance or orthostasis, should lead to consideration of a lower starting dose, slower titration, and careful monitoring during the initial dosing period in the elderly.  the mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients [ see  clinical pharmacology (12.3)and dosage and administration (2.3 )] . clinical experience with quetiapine in patients with renal impairment is limited [see clinical pharmacology (12.3)]. since quetiapine is extensively metabolized by the liver, higher plasma levels are expected in patients with hepatic impairment.  in this population, a low starting dose of 25 mg/day is recommended and the dose may be increased in increments of 25 mg/day - 50 mg/day [see  dosage and administration (2.4)and clinical pharmacology (12.3)] .  quetiapine is not a controlled substance. quetiapine has not been systematically studied, in animals or humans, for its potential for abuse, tolerance, or physical dependence. while the clinical trials did not reveal any tendency for any drug-seeking behavior, 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, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of misuse or abuse of quetiapine, e.g., development of tolerance, increases in dose, drug-seeking behavior.

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

pd-rx pharmaceuticals, inc. - amitriptyline hydrochloride (unii: 26lud4jo9k) (amitriptyline - unii:1806d8d52k) - amitriptyline hydrochloride 25 mg - for the relief of symptoms of depression. endogenous depression is more likely to be alleviated than are other depressive states. amitriptyline hydrochloride is contraindicated in patients who have shown prior hypersensitivity to it. it should not be given concomitantly with monoamine oxidase inhibitors. hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. when it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. amitriptyline hydrochloride should then be initiated cautiously with a gradual increase in dosage until optimum response is achieved. amitriptyline hydrochloride should not be given with cisapride due to the potential for increased qt interval and increased risk for arrhythmia. this drug is not recommended for use during the acute recovery phase following myocardial infa

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

pd-rx pharmaceuticals, inc. - amitriptyline hydrochloride (unii: 26lud4jo9k) (amitriptyline - unii:1806d8d52k) - amitriptyline hydrochloride 75 mg - for the relief of symptoms of depression. endogenous depression is more likely to be alleviated than are other depressive states. amitriptyline hydrochloride is contraindicated in patients who have shown prior hypersensitivity to it. it should not be given concomitantly with monoamine oxidase inhibitors. hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. when it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. amitriptyline hydrochloride should then be initiated cautiously with a gradual increase in dosage until optimum response is achieved. amitriptyline hydrochloride should not be given with cisapride due to the potential for increased qt interval and increased risk for arrhythmia. this drug is not recommended for use during the acute recovery phase following myocardial infa

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

pd-rx pharmaceuticals, inc. - amitriptyline hydrochloride (unii: 26lud4jo9k) (amitriptyline - unii:1806d8d52k) - amitriptyline hydrochloride 50 mg - for the relief of symptoms of depression. endogenous depression is more likely to be alleviated than are other depressive states. amitriptyline hydrochloride is contraindicated in patients who have shown prior hypersensitivity to it. it should not be given concomitantly with monoamine oxidase inhibitors. hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. when it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. amitriptyline hydrochloride should then be initiated cautiously with a gradual increase in dosage until optimum response is achieved. amitriptyline hydrochloride should not be given with cisapride due to the potential for increased qt interval and increased risk for arrhythmia. this drug is not recommended for use during the acute recovery phase following myocardial infa

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

pd-rx pharmaceuticals, inc. - amitriptyline hydrochloride (unii: 26lud4jo9k) (amitriptyline - unii:1806d8d52k) - amitriptyline hydrochloride 100 mg - for the relief of symptoms of depression. endogenous depression is more likely to be alleviated than are other depressive states. amitriptyline hydrochloride is contraindicated in patients who have shown prior hypersensitivity to it. it should not be given concomitantly with monoamine oxidase inhibitors. hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. when it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. amitriptyline hydrochloride should then be initiated cautiously with a gradual increase in dosage until optimum response is achieved. amitriptyline hydrochloride should not be given with cisapride due to the potential for increased qt interval and increased risk for arrhythmia. this drug is not recommended for use during the acute recovery phase following myocardial infa