Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - venlafaxine hydrochloride (unii: 7d7rx5a8mo) (venlafaxine - unii:grz5rcb1qg) - venlafaxine extended-release tablets are indicated for the treatment of major depressive disorder (mdd). efficacy of venlafaxine in mdd was shown in both short-term trials and a longer-term trial in mdd [ see clinical studies (14.1) ]. a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed mood or the loss of interest or pleasure in nearly all activities, representing a change from previous functioning, and includes the presence of at least five of the following nine symptoms during the same two-week period: depressed mood, markedly diminished interest or pleasure 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. venlafaxine extended-release tablets are indicated for the treatment of social anxiety disorder (sad), also known as social phobia, as defined in dsm-iv. social anxiety disorder (dsm-iv) is characterized by a marked and persistent fear of 1 or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others. exposure to the feared situation almost invariably provokes anxiety, which may approach the intensity of a panic attack. the feared situations are avoided or endured with intense anxiety or distress. the avoidance, anxious anticipation, or distress in the feared situation(s) interferes significantly with the person's normal routine, occupational or academic functioning, or social activities or relationships, or there is a marked distress about having the phobias. lesser degrees of performance anxiety or shyness generally do not require psychopharmacological treatment. efficacy of venlafaxine extended-release in the treatment of sad was established in short-term sad trials [ see clinical studies (14.2) ]. the use of maoi’s intended to treat psychiatric disorders with venlafaxine extended-release tablets or within 7 days of stopping treatment with venlafaxine extended-release tablets is contraindicated because of an increased risk of serotonin syndrome. the use of venlafaxine extended-release tablets within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated. [ see dosage and administration (2.6) and warnings and precautions (5.2) ]. starting venlafaxine extended-release 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 (2.7) and warnings and precautions (5.2) ]. 8.1 pregnancy based on data from published observational studies, exposure to snris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.13)and clinical considerations]. teratogenic effects venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m 2 basis. however, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. the cause of these deaths is not known. these effects occurred at 2.5 times (mg/m 2 ) the maximum human daily dose. the no effect dose for rat pup mortality was 0.25 times the human dose on a mg/m 2 basis. there are no adequate and well-controlled studies in pregnant women. because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. non-teratogenic effects neonates exposed to venlafaxine hydrochloride extended-release capsules, other snris (serotonin and norepinephrine reuptake inhibitors), or ssris (selective serotonin reuptake inhibitors), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [ see warnings and precautions (5.2) ]. when treating a pregnant woman with venlafaxine extended-release tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment maternal adverse reactions exposure to venlafaxine extended-release tablets in mid to late pregnancy may increase the risk of preeclampsia, and exposure to venlafaxine extended-release tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.13)]. the effect of venlafaxine on labor and delivery in humans is unknown. venlafaxine and odv have been reported to be excreted in human milk. because of the potential for serious adverse reactions in nursing infants from venlafaxine extended-release tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. safety and effectiveness in the pediatric population have not been established [ see boxed warning and warnings and precautions (5.1) ]. two placebo-controlled trials in 766 pediatric patients with mdd and two placebo-controlled trials in another disorder in 793 pediatric patients have been conducted with venlafaxine hydrochloride extended-release capsules, and the data were not sufficient to support a claim for use in pediatric patients. anyone considering the use of venlafaxine extended-release tablets in a child or adolescent must balance the potential risks with the clinical need. although no studies have been designed to primarily assess impact of venlafaxine hydrochloride extended-release capsules on the growth, development, and maturation of children and adolescents, the studies that have been done suggest that venlafaxine extended-release tablets may adversely affect weight and height [ see warnings and precautions (5.7, 5.8, and 5.9) ]. should the decision be made to treat a pediatric patient with venlafaxine extended-release tablets, regular monitoring of weight and height is recommended during treatment, particularly if it is to be continued long term. the safety of venlafaxine extended-release tablets treatment for pediatric patients has not been systematically assessed for chronic treatment longer than six months in duration. in the studies conducted in pediatric patients (ages 6-17), the occurrence of blood pressure and cholesterol increases considered to be clinically relevant in pediatric patients was similar to that observed in adult patients. consequently, the precautions for adults apply to pediatric patients [ see warnings and precautions (5.3 and 5.14) ].  approximately 4% (14/357) and 2% (6/277) of patients treated with venlafaxine hydrochloride extended-release capsules in placebo-controlled premarketing major depressive disorder and social anxiety disorder trials, respectively, were 65 years of age or over. of 2,897 patients treated with venlafaxine hydrochloride immediate-release tablets in premarketing phase major depressive disorder studies, 12% (357) were 65 years of age or over. no overall differences in effectiveness or safety were observed between geriatric patients and younger patients, and other reported clinical experience generally has not identified differences in response between the elderly and younger patients. however, greater sensitivity of some older individuals cannot be ruled out. ssris and snris, including venlafaxine hydrochloride extended-release capsules 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 (5.11) ]. the pharmacokinetics of venlafaxine and odv are not substantially altered in the elderly [ see clinical pharmacology (12.3) ]. no dose adjustment is recommended for the elderly on the basis of age alone, although other clinical circumstances, some of which may be more common in the elderly, such as renal or hepatic impairment, may warrant a dose reduction [ see dosage and administration (2.3) ]. in patients with cirrhosis of the liver, the clearances of venlafaxine and its active metabolite (odv) were decreased, thus prolonging the elimination half-lives of these substances. a large degree of intersubject variability was noted. [ see clinical pharmacology (12.3). ] a lower dose and individualization of dosing may be necessary [ see dosage and administration (2.3) ]. venlafaxine extended-release tablets, like all drugs effective in the treatment of major depressive disorder, should be used with caution in such patients. in patients with renal impairment (gfr = 10 to 70 ml/min), the clearances of venlafaxine and its active metabolites were decreased, thus prolonging the elimination half-lives of these substances [ see clinical pharmacology (12.3) ]. it is recommended that the total daily dose be reduced by 25% to 50% in patients with renal impairment. because there was much individual variability in clearance between patients with renal impairment, individualization of dosage may be desirable in some patients. in patients undergoing hemodialysis, it is recommended that the total daily dose be reduced by 50%. [s ee dosage and administration (2.3). ] venlafaxine extended-release tablets, like all drugs effective in the treatment of major depressive disorder, should be used with caution in such patients. venlafaxine extended-release tablets (venlafaxine hydrochloride) are not a controlled substance. while venlafaxine has not been systematically studied in clinical trials for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. however, it is not possible to predict on the basis of premarketing experience the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of venlafaxine (e.g., development of tolerance, incrementations of dose, drug-seeking behavior). in vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine, phencyclidine (pcp), or n-methyl-d-aspartic acid (nmda) receptors. venlafaxine was not found to have any significant cns stimulant activity in rodents. in primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability. discontinuation effects have been reported in patients receiving venlafaxine [see dosage and administration (2.4) and warnings and precautions (5.5)].

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - quetiapine fumarate (unii: 2s3pl1b6uj) (quetiapine - unii:bgl0jsy5si) - quetiapine extended-release tablets are indicated for the treatment of schizophrenia. the efficacy of quetiapine extended-release tablets in schizophrenia was established in one 6-week and one maintenance trial in adults with schizophrenia. efficacy was supported by three 6-week trials in adults with schizophrenia and one 6-week trial in adolescents with schizophrenia (13 to 17 years) treated with quetiapine tablets [see clinical studies (14.1)]. quetiapine extended-release tablets are indicated for the acute treatment of manic or mixed episodes associated with bipolar i disorder, both as monotherapy and as an adjunct to lithium or divalproex. the efficacy of quetiapine extended-release tablets in manic or mixed episodes of bipolar i disorder was established in one 3-week trial in adults with manic or mixed episodes associated with bipolar i disorder. efficacy was supported by two 12-week monotherapy trials

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - quetiapine fumarate (unii: 2s3pl1b6uj) (quetiapine - unii:bgl0jsy5si) - quetiapine extended-release tablets are indicated for the treatment of schizophrenia. the efficacy of quetiapine extended-release tablets in schizophrenia was established in one 6-week and one maintenance trial in adults with schizophrenia. efficacy was supported by three 6-week trials in adults with schizophrenia and one 6-week trial in adolescents with schizophrenia (13 to 17 years) treated with quetiapine tablets [see clinical studies (14.1)]. quetiapine extended-release tablets are indicated for the acute treatment of manic or mixed episodes associated with bipolar i disorder, both as monotherapy and as an adjunct to lithium or divalproex. the efficacy of quetiapine extended-release tablets in manic or mixed episodes of bipolar i disorder was established in one 3-week trial in adults with manic or mixed episo

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder in adults - generalized anxiety disorder in adults and pediatric patients 7 years of age and older - diabetic peripheral neuropathic pain in adults - fibromyalgia in adults and pediatric patients 13 years of age and older - chronic musculoskeletal pain in adults the use of maois intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration ( 2.8) and warnings and precautions ( 5.4)]. starting duloxetine 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 ( 2.9) and warnings and precautions ( 5.4)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors the pregnancy outcomes in women exposed to antidepressants, including duloxetine, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for antidepressants at 1-866-961-2388 or online at https://womensmentalhealth.org/research/pregnancyregistry/. risk summary data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see data) . there are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to snris and ssris, including duloxetine, during pregnancy (see clinical considerations). in rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 times and 6 times, respectively, the maximum recommended human dose (mrhd) of 120 mg/day given to adolescents on a mg/m 2 basis. when duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the mrhd given to adolescents on a mg/m 2 basis. at this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. post-weaning growth was not adversely affected. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk 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 that followed 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. pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis. it is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. maternal adverse reactions use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions ( 5.5)]. fetal/neonatal adverse reaction neonates exposed to duloxetine and other snris or ssris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these findings are consistent with either a direct toxic effect of the snris or 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 ( 5.4)] . data human data data from a postmarketing retrospective claims-based cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% ci: 1.08 to 2.18). the same study did not find a clinically meaningful increase in the risk for major birth defects in the comparison of 2532 women exposed to duloxetine in the first trimester of pregnancy to 1,284,827 unexposed women after adjusting for several confounders. methodologic limitations include possible residual confounding, misclassification of exposure and outcomes, lack of direct measures of disease severity, and lack of information about alcohol use, nutrition, and over-the-counter medication exposures. animal data in animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. when duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of malformations or developmental variations at doses up to 45 mg/kg/day [3 times and 6 times, respectively, the mrhd of 120 mg/day given to adolescents on a mg/m 2 basis]. however, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (approximately equal to the mrhd in rats and 2 times the mrhd in rabbits). when duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (2 times the mrhd given to adolescents on a mg/m 2 basis); the no-effect dose was 10 mg/kg/day. furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. risk summary data from published literature report the presence of duloxetine in human milk (see data) . there are reports of sedation, poor feeding, and poor weight gain in infants exposed to duloxetine through breast milk (see clinical considerations) . there are no data on the effect of duloxetine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for duloxetine and any potential adverse effects on the breastfed child from duloxetine or from the underlying maternal condition. clinical considerations infants exposed to duloxetine should be monitored for sedation, poor feeding and poor weight gain. data disposition of duloxetine was studied in 6 lactating women who were at least 12 weeks postpartum and had elected to wean their infants. the women were given 40 mg of duloxetine twice daily for 3.5 days. the peak concentration measured in breast milk occurred at a median of 3 hours after the dose. the amount of duloxetine in breast milk was approximately 7 mcg/day while on that dose; the estimated daily infant dose was approximately 2 mcg/kg/day, which is less than 1% of the maternal dose. the presence of duloxetine metabolites in breast milk was not examined. the safety and effectiveness of duloxetine have been established for treatment of generalized anxiety disorder (gad) in patients 7 years to 17 years of age and for treatment of juvenile fibromyalgia syndrome in patients 13 years to 17 years of age. the safety and effectiveness of duloxetine have not been established in pediatric patients with major depressive disorder (mdd), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain. antidepressants increased the risk of suicidal thoughts and behavior in pediatric patients. monitor all pediatric patients being treated with antidepressants for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment, or at times of dosage changes [see warnings and precautions ( 5.1)] . perform regular monitoring of weight and growth in pediatric patients treated with duloxetine [see adverse reactions ( 6.1)]. generalized anxiety disorder use of duloxetine for the treatment of gad in patients 7 years to 17 years of age is supported by one 10-week, placebo-controlled trial (gad-6). the study included 272 pediatric patients with gad of which 47% were 7 years to 11 years of age (53% were 12 years to 17 years of age). duloxetine demonstrated superiority over placebo as measured by greater improvement in the pediatric anxiety rating scale (pars) for gad severity score [see clinical studies ( 14.3)]. the safety and effectiveness of duloxetine for the treatment of gad in pediatric patients less than 7 years of age have not been established. fibromyalgia use of duloxetine for treatment of fibromyalgia in patients 13 years to 17 years of age is supported by a 13-week placebo-controlled trial in 184 patients with juvenile fibromyalgia syndrome (study fm-4). duloxetine showed improvement over placebo on the primary endpoint, change from baseline to end-of-treatment on the brief pain inventory (bpi) – modified short form: adolescent version 24-hour average pain severity rating [see clinical studies (14.5)]. the safety and effectiveness of duloxetine for the treatment of fibromyalgia in patients less than 13 years of age have not been established. major depressive disorder the safety and effectiveness of duloxetine have not been established in pediatric patients for the treatment of mdd. efficacy of duloxetine was not demonstrated in two 10-week, placebo-controlled trials with 800 pediatric patients aged 7 years to 17 years old with mdd (mdd-6 and mdd-7). neither duloxetine nor an active control (approved for treatment of pediatric mdd) was superior to placebo. the most frequently observed adverse reactions in the mdd pediatric clinical trials included nausea, headache, decreased weight, and abdominal pain. decreased appetite and weight loss have been observed in association with the use of ssris and snris. juvenile animal toxicology data duloxetine administration to young rats from post-natal day 21 (weaning) through post-natal day 90 (adult) resulted in decreased body weights that persisted into adulthood, but recovered when drug treatment was discontinued; slightly delayed (~1.5 days) sexual maturation in females, without any effect on fertility; and a delay in learning a complex task in adulthood, which was not observed after drug treatment was discontinued. these effects were observed at the high dose of 45 mg/kg/day (2 times the mrhd, for a child); the no-effect-level was 20 mg/kg/day (≈1 times the mrhd, for a child). geriatric exposure in premarketing clinical trials of duloxetine - of the 2,418 patients in mdd trials, 6% (143) were 65 years of age or over. - of the 1,041 patients in clbp trials, 21% (221) were 65 years of age or over. - of the 487 patients in oa trials, 41% (197) were 65 years of age or over. - of the 1,074 patients in the dpnp trials, 33% (357) were 65 years of age or over. - of the 1,761 patients in fm trials, 8% (140) were 65 years of age or over. in the mdd, gad, dpnp, fm, oa, and clbp studies, no overall differences in safety or effectiveness were generally observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between these geriatric and younger adult patients, but greater sensitivity of some older patients cannot be ruled out. ssris and snris, including duloxetine have been associated with clinically significant hyponatremia in geriatric patients, who may be at greater risk for this adverse reaction [see warnings and precautions ( 5.13)] . in an analysis of data from all placebo-controlled-trials, duloxetine -treated patients reported a higher rate of falls compared to placebo-treated patients. the increased risk appears to be proportional to a patient’s underlying risk for falls. underlying risk appears to increase steadily with age. as geriatric patients tend to have a higher prevalence of risk factors for falls such as medications, medical comorbidities and gait disturbances, the impact of increasing age by itself on falls during duloxetine treatment is unclear. falls with serious consequences including bone fractures and hospitalizations have been reported with duloxetine use [see warnings and precautions ( 5.3) and adverse reactions ( 6.1)] . the pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females (65 years to 77 years) and healthy middle-age females (32 years to 50 years). there was no difference in the c max , but the auc of duloxetine was somewhat (about 25%) higher and the half-life about 4 hours longer in the elderly females. population pharmacokinetic analyses suggest that the typical values for clearance decrease by approximately 1% for each year of age between 25 years to 75 years of age; but age as a predictive factor only accounts for a small percentage of between-patient variability. dosage adjustment based on the age of the adult patient is not necessary. duloxetine's half-life is similar in men and women. dosage adjustment based on gender is not necessary. duloxetine bioavailability (auc) appears to be reduced by about one-third in smokers. dosage modifications are not recommended for smokers. no specific pharmacokinetic study was conducted to investigate the effects of race. patients with clinically evident hepatic impairment have decreased duloxetine metabolism and elimination. after a single 20 mg dose of duloxetine, 6 cirrhotic patients with moderate liver impairment (child-pugh class b) had a mean plasma duloxetine clearance about 15% that of age- and gender-matched healthy subjects, with a 5-fold increase in mean exposure (auc). although c max was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see dosage and administration ( 2.7) and warnings and precautions ( 5.14)] . limited data are available on the effects of duloxetine in patients with end-stage renal disease (esrd). after a single 60 mg dose of duloxetine, c max and auc values were approximately 100% greater in patients with esrd receiving chronic intermittent hemodialysis than in subjects with normal renal function. the elimination half-life, however, was similar in both groups. the aucs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing. population pk analyses suggest that mild to moderate degrees of renal impairment (estimated crcl 30 to 80 ml/min) have no significant effect on duloxetine apparent clearance [see dosage and administration ( 2.7) and warnings and precautions ( 5.14)] . in animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. while duloxetine has not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. however, it is not possible to predict on the basis of premarketing experience the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of duloxetine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior). in drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats.

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram 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 solutions. 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. risk summary based on data form published observational studies, exposure to ssris, particulary in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warning 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/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 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 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 solutions. 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).

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - desmopressin acetate (unii: xb13hyu18u) (desmopressin - unii:enr1llb0fp) - desmopressin acetate 0.1 mg - desmopressin acetate tablets are indicated as antidiuretic replacement therapy in the management of central diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. desmopressin acetate tablets are ineffective for the treatment of nephrogenic diabetes insipidus. patients were selected for therapy based on the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or response to antidiuretic hormone. continued response to desmopressin acetate can be monitored by measuring urine volume and osmolality. desmopressin acetate tablets are indicated for the management of primary nocturnal enuresis. desmopressin acetate tablets may be used alone or as an adjunct to behavioral conditioning or other non-pharmacologic intervention. desmopressin acetate tablets are contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of desmopressin acetate tablet

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - isosorbide dinitrate (unii: ia7306519n) (isosorbide dinitrate - unii:ia7306519n) - isosorbide dinitrate tablets, usp are indicated for the prevention of angina pectoris due to coronary artery disease. the onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode. isosorbide dinitrate tablets are contraindicated in patients who are allergic to isosorbide dinitrate or any of its ingredients. do not use isosorbide dinitrate tablets in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil. concomitant use can cause severe hypotension, syncope, or myocardial ischemia. do not use isosorbide dinitrate tablets in patients who are taking the soluble guanylate cyclase stimulator riociguat. concomitant use can cause hypotension.

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - nitrofurantoin (unii: 927ah8112l) (nitrofurantoin - unii:927ah8112l), nitrofurantoin monohydrate (unii: e1qi2cqq1i) (nitrofurantoin - unii:927ah8112l) - nitrofurantoin capsules, usp (monohydrate/ macrocrystals) are indicated only for the treatment of acute uncomplicated urinary tract infections (acute cystitis) caused by susceptible strains of escherichia coli or staphylococcus saprophyticus . nitrofurantoin is not indicated for the treatment of pyelonephritis or perinephric abscesses. to reduce the development of drug-resistant bacteria and maintain the effectiveness of nitrofurantoin capsules, usp (monohydrate/ macrocrystals) and other antibacterial drugs,nitrofurantoin capsules, usp (monohydrate/ macrocrystals)  should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. nitrofurantoins lack the broader tissue distribut

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - leucovorin calcium (unii: rpr1r4c0p4) (leucovorin - unii:q573i9dvlp) - leucovorin 10 mg in 1 ml - leucovorin calcium rescue is indicated after high dose methotrexate therapy in osteosarcoma. leucovorin calcium is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. leucovorin calcium is indicated in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible. leucovorin is also indicated for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. leucovorin should not be mixed in the same infusion as 5-fluorouracil because a precipitate may form. leucovorin is improper therapy for pernicious anemia and other megaloblastic anemias secondary to the lack of vitamin b12 . a hematologic remission may occur while neurologic manifestations continue to progress.

Marekani - Kiingereza - NLM (National Library of Medicine)

bluepoint laboratories - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1) - diclofenac sodium 75 mg - carefully consider the potential benefits and risks of diclofenac sodium delayed-release tablets and other treatment options before deciding to use diclofenac sodium delayed-release tablets. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings: gastrointestinal bleeding, ulceration and perforation ). diclofenac sodium delayed-release tablets are indicated: - for relief of the signs and symptoms of osteoarthritis - for relief of the signs and symptoms of rheumatoid arthritis - for acute or long-term use in the relief of signs and symptoms of ankylosing spondylitis diclofenac sodium delayed-release tablets are contraindicated in the following patients. - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product (see warnings: anaphylactic reactions , serious skin reacti