미국 - 영어 - NLM (National Library of Medicine)

cadila pharmaceuticals limited - nateglinide (unii: 41x3pwk4o2) (nateglinide - unii:41x3pwk4o2) - nateglinide tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use : nateglinide tablets should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. nateglinide is contraindicated in patients with a history of hypersensitivity to nateglinide or its inactive ingredients. risk summary  the available data from published literature and the applicant’s pharmacovigilance with use of nateglinide in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see clinical considerations) . nateglinide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. in animal reproduction studies, there was no teratogenicity in rats and rabbits administer

미국 - 영어 - NLM (National Library of Medicine)

cadila pharmaceuticals limited - olanzapine (unii: n7u69t4szr) (olanzapine - unii:n7u69t4szr) - oral olanzapine is indicated for the treatment of schizophrenia. efficacy was established in three clinical trials in adult patients with schizophrenia: two 6-week trials and one maintenance trial. in adolescent patients with schizophrenia (ages 13 to 17), efficacy was established in one 6-week trial [see clinical studies (14.1)]. when deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see warnings and precautions (5.5)]. monotherapy — oral olanzapine is indicated for the acute treatment of manic or mixed episodes associated with bipolar i disorder and maintenance treatment of bipolar i disorder. efficacy was established in three clinical trials in adult patients with manic or mixed episodes of bipolar i disorder: two 3- to 4-week trials and one monotherapy maintenance trial. in adolescent patients with manic or mixed episodes associated with bipolar i disorder (ages 13 to 17), efficacy was established in one 3-week trial [see clinical studies (14.2)]. when deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see warnings and precautions (5.5)]. adjunctive therapy to lithium or valproate — oral olanzapine is indicated for the treatment of manic or mixed episodes associated with bipolar i disorder as an adjunct to lithium or valproate. efficacy was established in two 6-week clinical trials in adults. the effectiveness of adjunctive therapy for longer-term use has not been systematically evaluated in controlled 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, pediatric 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 should be part of a total treatment program that often includes psychological, educational and social interventions. olanzapine intramuscular is indicated for the treatment of acute agitation associated with schizophrenia and bipolar i mania. efficacy was demonstrated in 3 short-term (24 hours of im treatment) placebo-controlled trials in agitated adult inpatients with: schizophrenia or bipolar i disorder (manic or mixed episodes) [see clinical studies (14.3)] . “psychomotor agitation” is defined in dsm-iv as “excessive motor activity associated with a feeling of inner tension.” patients experiencing agitation often manifest behaviors that interfere with their diagnosis and care, e.g., threatening behaviors, escalating or urgently distressing behavior, or self-exhausting behavior, leading clinicians to the use of intramuscular antipsychotic medications to achieve immediate control of the agitation. oral olanzapine and fluoxetine in combination is indicated for the treatment of depressive episodes associated with bipolar i disorder, based on clinical studies. when using olanzapine and fluoxetine in combination, refer to the clinical studies section of the package insert for symbyax. olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar i disorder. oral olanzapine and fluoxetine in combination is indicated for the treatment of treatment resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode), based on clinical studies in adult patients. when using olanzapine and fluoxetine in combination, refer to the clinical studies section of the package insert for symbyax. olanzapine monotherapy is not indicated for the treatment of treatment resistant depression. • none with olanzapine monotherapy. (4) • when using olanzapine and fluoxetine in combination, also refer to the contraindications section of the package insert for symbyax. • for specific information about the contraindications of lithium or valproate, refer to the contraindications section of the package inserts for these other products. when using olanzapine and fluoxetine in combination, also refer to the use in specific populations section of the package insert for symbyax. pregnancy exposure registry     there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including olanzapine, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.  risk summary neonates exposed to antipsychotic drugs, including olanzapine, 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 olanzapine 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 or bipolar i disorder and with exposure to antipsychotics, including olanzapine, during pregnancy (see clinical considerations).   olanzapine was not teratogenic when administered orally to pregnant rats and rabbits at doses that are 9- and 30-times the daily oral maximum recommended human dose (mrhd), based on mg/m2 body surface area;some fetal toxicities were observed at these doses (see data). the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. all pregnancies have a background risk of birth defects, 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 embryo/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. 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 olanzapine, during the third trimester of pregnancy. these symptoms have 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 placental passage has been reported in published study reports; however, the placental passage ratio was highly variable ranging between 7% to 167% at birth following exposure during pregnancy. the clinical relevance of this finding is unknown. published data from observational studies, birth registries, and case reports that have evaluated the use of atypical antipsychotics during pregnancy do not establish an increased risk of 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 for major birth defects. animal data in oral reproduction studies in rats at doses up to 18 mg/kg/day and in rabbits at doses up to 30 mg/kg/day (9 and 30 times the daily oral mrhd based on mg/m2 body surface area, respectively), no evidence of teratogenicity was observed. in an oral rat teratology study, early resorptions and increased numbers of nonviable fetuses were observed at a dose of 18 mg/kg/day (9 times the daily oral mrhd based on mg/m2 body surface area), and gestation was prolonged at 10 mg/kg/day (5 times the daily oral mrhd based on mg/m2 body surface area). in an oral rabbit teratology study, fetal toxicity manifested as increased resorptions and decreased fetal weight, occurred at a maternally toxic dose of 30 mg/kg/day (30 times the daily oral mrhd based on mg/m2 body surface area). risk summary olanzapine is present in human milk. there are reports of excess sedation, irritability, poor feeding and extrapyramidal symptoms (tremors and abnormal muscle movements) in infants exposed to olanzapine through breast milk (see clinical considerations). there is no information on the effects of olanzapine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for olanzapine and any potential adverse effects on the breastfed child from olanzapine or from the mother’s underlying condition. clinical considerations infants exposed to olanzapine should be monitored for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements). infertility females based on the pharmacologic action of olanzapine (d2 receptor antagonism), treatment with olanzapine 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)]. the safety and effectiveness of oral olanzapine in the treatment of schizophrenia and manic or mixed episodes associated with bipolar i disorder were established in short-term studies in adolescents (ages 13 to 17 years). use of olanzapine in adolescents is supported by evidence from adequate and well-controlled studies of olanzapine in which 268 adolescents received olanzapine in a range of 2.5 to 20 mg/day [see clinical studies (14.1, 14.2)] . recommended starting dose for adolescents is lower than that for adults [see dosage and administration (2.1, 2.2)] . compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, ldl cholesterol, prolactin and hepatic aminotransferase levels [see warnings and precautions  (5.5, 5.15, 5.17) and adverse reactions (6.1)] . when deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see indications and usage (1.1, 1.2)] . safety and effectiveness of olanzapine in children <13 years of age have not been established [see patient counseling information (17)] . safety and efficacy of olanzapine and fluoxetine in combination in children and adolescents (10 to 17 years of age) have been established for the acute treatment of depressive episodes associated with bipolar i disorder. safety and effectiveness of olanzapine and fluoxetine in combination in children <10 years of age have not been established. of the 2,500 patients in premarketing clinical studies with oral olanzapine, 11% (263) were 65 years of age or over. in patients with schizophrenia, there was no indication of any different tolerability of olanzapine in the elderly compared to younger patients. studies in elderly patients with dementia-related psychosis have suggested that there may be a different tolerability profile in this population compared to younger patients with schizophrenia. elderly patients with dementia- related psychosis treated with olanzapine are at an increased risk of death compared to placebo. in placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis, there was a higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in patients treated with olanzapine compared to patients treated with placebo. in 5 placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis (n=1,184), the following adverse reactions were reported in olanzapine-treated patients at an incidence of at least 2% and significantly greater than placebo-treated patients: falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth and visual hallucinations. the rate of discontinuation due to adverse reactions was greater with olanzapine than placebo (13% vs 7%). elderly patients with dementia-related psychosis treated with olanzapine are at an increased risk of death compared to placebo. olanzapine is not approved for the treatment of patients with dementia-related psychosis [see boxed warning, warnings and precautions (5.1), and patient counseling information (17) ]. olanzapine is not approved for the treatment of patients with dementia-related psychosis. also, the presence of factors that might decrease pharmacokinetic clearance or increase the pharmacodynamic response to olanzapine should lead to consideration of a lower starting dose for any geriatric patient [see boxed warning, dosage and administration (2.1),and warnings and precautions (5.1)]. clinical studies of olanzapine and fluoxetine in combination did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients. in studies prospectively designed to assess abuse and dependence potential, olanzapine was shown to have acute depressive cns effects but little or no potential of abuse or physical dependence in rats administered oral doses up to 15 times the daily oral mrhd (20 mg) and rhesus monkeys administered oral doses up to 8 times the daily oral mrhd based on mg/m2 body surface area. olanzapine has not been systematically studied in 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 olanzapine (e.g., development of tolerance, increases in dose, drug-seeking behavior).

미국 - 영어 - NLM (National Library of Medicine)

cadila pharmaceuticals limited - 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 are 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 administrations (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 administrations   (2.7) and warnings and precautions (5.2)] . 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/m2 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/m2 ) the maximum human daily dose. the no effect dose for rat pup mortality was 0.25 times the human dose on a mg/m2 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 to 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%. [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. 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)] .

미국 - 영어 - NLM (National Library of Medicine)

cadila pharmaceuticals limited - paroxetine hydrochloride hemihydrate (unii: x2els050d8) (paroxetine - unii:41vrh5220h) - paroxetine extended-release tablets are indicated in adults for the treatment of: • major depressive disorder (mdd) • panic disorder (pd) • social anxiety disorder (sad) • premenstrual dysphoric disorder (pmdd) paroxetine extended-release tablets are contraindicated in patients: • taking, or within 14 days of stopping, maois (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome      [see warnings and precautions (5.2), drug interactions (7)] . • taking thioridazine because of risk of qt prolongation [see warnings and precautions (5.3), drug interactions (7)] . • taking pimozide because of risk of qt prolongation [see warnings and precautions (5.3), drug interactions (7)]. • with known hypersensitivity (e.g., anaphylaxis, angioedema, stevens-johnson syndrome) to paroxetine or to any of the inactive ingredients in paroxetine extended-release tablets [see adverse reactions (6.1, 6.2)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/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 (5.5) and clinical considerations] . paroxetine extended-release tablets are associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. while individual epidemiological studies on the association between paroxetine use and cardiovascular malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see data ). there are risks of persistent pulmonary hypertension of the newborn (pphn) (see data ) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (ssris), including paroxetine extended-release tablets, during pregnancy. there also are risks associated with untreated depression in pregnancy (see clinical considerations ). for women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. no evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. these doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (mrhd – 75 mg) on an mg/m2 basis. when paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. this effect occurred at a dose of 1 mg/kg/day which is less than the mrhd on an mg/m2 basis ( see data) . the estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the us 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 of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of paroxetine extended-release tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.5)] . fetal/neonatal adverse reactions neonates exposed to paroxetine extended-release tablets and other 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, tremors, jitteriness, irritability, and constant crying. these findings are consistent with either a direct toxic effect of ssris or possibly a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.4)] . data human data published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996-2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. specific cardiac malformations identified in two meta-analyses include approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. one meta-analysis also identified an increased risk (less than 2- fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defects (pooled or 2.38, 95% ci 1.14-4.97). important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity, and potential exposure misclassification. exposure to ssris, particularly later in pregnancy, may have an increased risk for pphn. pphn occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. animal data reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. these doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (mrhd – 75 mg) on an mg/m2 basis. these studies have revealed no evidence of malformations. however, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. this effect occurred at a dose of 1 mg/kg/day which is less than the mrhd on an mg/m2 basis. the no-effect dose for rat pup mortality was not determined. the cause of these deaths is not known. risk summary data from the published literature report the presence of paroxetine in human milk (see data). there are reports of agitation, irritability, poor feeding and poor weight gain in infants exposed to paroxetine through breast milk (see clinical considerations) . there are no data on the effects of paroxetine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for paroxetine extended-release tablets and any potential adverse effects on the breastfed infant from paroxetine extended-release tablets or the underlying maternal condition. clinical considerations  infants exposed to paroxetine extended-release tablets should be monitored for agitation, irritability, poor feeding and poor weight gain. data published literature suggests the presence of paroxetine in human milk with relative infant doses ranging between 0.4% to 2.2%, and a milk: plasma ratio of <1. no significant amounts were detected in the plasma of infants after breastfeeding. infertility male based on findings from clinical studies, paroxetine may affect sperm quality which may impair fertility; it is not known if this effect is reversible [see nonclinical toxicology (13.1) ]. the safety and effectiveness of paroxetine extended-release tablets in pediatric patients have not been established [see boxed warning, warnings and precautions (5.1)]. three placebo-controlled trials in 752 pediatric patients with mdd have been conducted with immediate-release paroxetine, and effectiveness was not established in pediatric patients. decreased appetite and weight loss have been observed in association with the use of ssris. in placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with immediate-release paroxetine hydrochloride and at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. adverse reactions upon discontinuation of treatment with immediate-release paroxetine hydrochloride in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain. ssris and snris, including paroxetine extended-release tablets, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.9)]. in premarketing clinical trials with immediate-release paroxetine hydrochloride, 17% of paroxetine treated patients (approximately 700) were 65 years or older. pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between these subjects and younger subjects [see dosage and administration (2.5), clinical pharmacology (12.3)]. increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. the initial dosage of paroxetine extended-release tablets should be reduced in patients with severe renal impairment and patients with severe hepatic impairment [see dosage and administration (2.5) and clinical pharmacology (12.3)].

미국 - 영어 - NLM (National Library of Medicine)

cadila pharmaceuticals limited - sildenafil citrate (unii: bw9b0ze037) (sildenafil - unii:3m7ob98y7h) - sildenafil tablets are indicated for the treatment of erectile dysfunction. consistent with its known effects on the nitric oxide/cgmp pathway [see clinical pharmacology (12.1, 12.2)] , sildenafil tablets were shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using nitric oxide donors such as organic nitrates or organic nitrites in any form either regularly and/or intermittently is therefore contraindicated. after patients have taken sildenafil tablets, it is unknown when nitrates, if necessary, can be safely administered. although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [see dosage and administration (2.3), drug interactions (7.1), and clinical pharmacology (12.2)]. sildenafil tablets are contraindicated in patients with a known hypersensitivity to sildenafil, as contained in sildenafil tablets and revatio, or any component of the tablet. hypersensitivity reactions have been reported, including rash and urticaria [see adverse reactions (6.1)] . do not use sildenafil tablets in patients who are using a gc stimulator, such as riociguat. pde5 inhibitors, including sildenafil tablets, may potentiate the hypotensive effects of gc stimulators. risk summary sildenafil tablets are not indicated for use in females. there are no data with the use of sildenafil tablets in pregnant women to inform any drug-associated risks for adverse developmental outcomes. animal reproduction studies conducted with sildenafil did not show adverse developmental outcomes when administered during organogenesis in rats and rabbits at oral doses up to 16 and 32 times, respectively, the maximum recommended human dose (mrhd) of 100 mg/day on a mg/m2 basis (see data). data animal data no evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received oral doses up to 200 mg/kg/day during organogenesis. these doses represent, respectively, about 16 and 32 times the mrhd on a mg/m2 basis in a 50 kg subject. in the rat pre- and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days, about 2 times the mrhd on a mg/m2 basis in a 50 kg subject. risk summary sildenafil tablets are not indicated for use in females. limited data indicate that sildenafil and its active metabolite are present in human milk. there is no information on the effects on the breastfed child, or the effects on milk production sildenafil tablets are not indicated for use in pediatric patients. safety and effectiveness have not been established in pediatric patients. healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil resulting in approximately 84% and 107% higher plasma auc values of sildenafil and its active n-desmethyl metabolite, respectively, compared to those seen in healthy young volunteers (18 to 45 years) [see clinical pharmacology (12.3)] . due to age-differences in plasma protein binding, the corresponding increase in the auc of free (unbound) sildenafil and its active n-desmethyl metabolite were 45% and 57%, respectively [see clinical pharmacology (12.3)].   of the total number of subjects in clinical studies of sildenafil tablets, 18% were 65 years and older, while 2% were 75 years and older. no overall differences in safety or efficacy were observed between older (≥ 65 years of age) and younger (< 65 years of age) subjects.  however, since higher plasma levels may increase the incidence of adverse reactions, a starting dose of 25 mg should be considered in older subjects due to the higher systemic exposure [see dosage and administration (2.5)] . no dose adjustment is required for mild (clcr=50 to 80 ml/min) and moderate (clcr=30 to 49 ml/min) renal impairment. in volunteers with severe renal impairment (clcr<30 ml/min), sildenafil clearance was reduced, resulting in higher plasma exposure of sildenafil (~2 fold), approximately doubling of cmax and auc. a starting dose of 25 mg should be considered in patients with severe renal impairment [see dosage and administration (2.5) and clinical pharmacology (12.3)]. in volunteers with hepatic impairment (child-pugh class a and b), sildenafil clearance was reduced, resulting in higher plasma exposure of sildenafil (47% for cmax and 85% for auc). the pharmacokinetics of sildenafil in patients with severely impaired hepatic function (child-pugh class c) have not been studied. a starting dose of 25 mg should be considered in patients with any degree of hepatic impairment [see dosage and administration (2.5) and clinical pharmacology (12.3)].

영국 - 영어 - MHRA (Medicines & Healthcare Products Regulatory Agency)

kent pharma (uk) ltd - pantoprazole sodium sesquihydrate - gastro-resistant tablet - 40mg

미국 - 영어 - NLM (National Library of Medicine)

cadila pharmaceuticals limited - telmisartan (unii: u5syw473rq) (telmisartan - unii:u5syw473rq) - telmisartan 20 mg - telmisartan tablets, usp are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a v

미국 - 영어 - NLM (National Library of Medicine)

cadila pharmaceuticals limited - nebivolol hydrochloride (unii: jgs34j7l9i) (nebivolol - unii:030y90569u) - nebivolol tablets are indicated for the treatment of hypertension, to lower blood pressure [see clinical studies ( 14.1 ) ]. nebivolol may be used alone or in combination with other antihypertensive agents [see drug interactions ( 7 )]. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including the class to which this drug principally belongs. there are no controlled trials demonstrating risk reduction with nebivolol. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as

필리핀 - 영어 - FDA (Food And Drug Administration)

cadila pharamceuticals limited - drug - montelukast (as sodium) - aerokids

뉴질랜드 - 영어 - Medsafe (Medicines Safety Authority)

pharmacy retailing (nz) ltd t/a healthcare logistics - ethambutol hydrochloride 100mg - tablet - 100 mg - active: ethambutol hydrochloride 100mg excipient: gelatin magnesium stearate methylated spirits opaglos clear na-7150 purified talc quinoline yellow shellac sorbitol stearic acid sucrose - myambutol is indicated for the treatment of pulmonary tuberculosis, primary tuberculosis and extrapulmonary forms of tuberculosis, including miliary tuberculosis, tuberculous meningitis, tuberculosis of bones and joints, genitourinary tuberculosis, tuberculosis of the skin and tuberculous eye diseases.