संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

dr. reddy's laboratories inc. - olanzapine (unii: n7u69t4szr) (olanzapine - unii:n7u69t4szr) - olanzapine 5 mg - 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) ].  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 episode

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

aurobindo pharma limited - olanzapine (unii: n7u69t4szr) (olanzapine - unii:n7u69t4szr) - olanzapine 2.5 mg - oral olanzapine tablets are 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 tablets are 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 patie

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

zydus lifesciences limited - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 125 mg -   divalproex sodium delayed-release capsules (sprinkle) are indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. divalproex sodium delayed-release capsules (sprinkle) are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.    simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. complex absence is the term used when other signs are also present. because of the risk to the fetus of decreased iq, neurodevelopmental disorders, neural tube defects, and other major congenital malformations, which may occur very early in pregnancy, valproate should not

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

ascend laboratories, llc - olanzapine (unii: n7u69t4szr) (olanzapine - unii:n7u69t4szr) - olanzapine 2.5 mg - 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 mi

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

zydus pharmaceuticals usa inc. - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 125 mg -   divalproex sodium delayed-release capsules are indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. divalproex sodium delayed-release capsules are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.    simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. complex absence is the term used when other signs are also present. because of the risk to the fetus of decreased iq, neurodevelopmental disorders, neural tube defects, and other major congenital malformations, which may occur very early in pregnancy, valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see warnings and precautions (5.2, 5.3, 5.4), use in specific populations (8.1), and patient counseling information (17)] . for prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)] . - divalproex sodium delayed-release capsules should not be administered to patients with hepatic disease or significant hepatic dysfunction [see warnings and precautions (5.1)]. - divalproex sodium delayed-release capsules are contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial dna polymerase γ (polg; e.g., alpers-huttenlocher syndrome) and children under two years of age who are suspected of having a polg-related disorder [see warnings and precautions (5.1)] . - divalproex sodium delayed-release capsules are contraindicated in patients with known hypersensitivity to the drug [see warnings and precautions (5.12)]. - divalproex sodium delayed-release capsules are contraindicated in patients with known urea cycle disorders [see warnings and precautions (5.6)]. - for use in prophylaxis of migraine headaches: divalproex sodium delayed-release capsules are contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see warnings and precautions (5.2,5.3, 5.4) and use in specific populations (8.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), including divalproex sodium delayed-release capsules, during pregnancy. encourage women who are taking divalproex sodium delayed-release capsules during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling toll-free 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/. this must be done by the patient herself. risk summary for use in prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)] . for use in epilepsy or bipolar disorder, valproate should not be used to treat women who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see boxed warning and warnings and precautions (5.2, 5.3)] . women with epilepsy who become pregnant while taking valproate should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects including spina bifida, but also malformations involving other body systems (e.g., craniofacial defects including oral clefts, cardiovascular malformations, hypospadias, limb malformations). this risk is dose-dependent; however, a threshold dose below which no risk exists cannot be established. in utero exposure to valproate may also result in hearing impairment or hearing loss. valproate polytherapy with other aeds has been associated with an increased frequency of congenital malformations compared with aed monotherapy. the risk of major structural abnormalities is greatest during the first trimester; however, other serious developmental effects can occur with valproate use throughout pregnancy. the rate of congenital malformations among babies born to epileptic mothers who used valproate during pregnancy has been shown to be about four times higher than the rate among babies born to epileptic mothers who used other anti-seizure monotherapies [see warnings and precautions (5.2) and data (human)] . epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores and a higher risk of neurodevelopmental disorders compared to children exposed to either another aed in utero or to no aeds in utero [see warnings and precautions (5.3) and data (human)] . an observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders [see data (human)] . in animal studies, valproate administration during pregnancy resulted in fetal structural malformations similar to those seen in humans and neurobehavioral deficits in the offspring at clinically relevant doses [see data (animal)] . there have been reports of hypoglycemia in neonates and fatal cases of hepatic failure in infants following maternal use of valproate during pregnancy. pregnant women taking valproate may develop hepatic failure or clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see warnings and precautions (5.1, 5.8)] . available prenatal diagnostic testing to detect neural tube and other defects should be offered to pregnant women using valproate. evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. it is not known whether the risk of neural tube defects or decreased iq in the offspring of women receiving valproate is reduced by folic acid supplementation. dietary folic acid supplementation both prior to conception and during pregnancy should be routinely recommended for patients using valproate [see warnings and precautions (5.2, 5.4)] . 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 to prevent major seizures, women with epilepsy should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. even minor seizures may pose some hazard to the developing embryo or fetus [see warnings and precautions (5.4)] . however, discontinuation of the drug may be considered prior to and during pregnancy in individual cases if the seizure disorder severity and frequency do not pose a serious threat to the patient. maternal adverse reactions pregnant women taking valproate may develop clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see warnings and precautions (5.8)] . if valproate is used in pregnancy, the clotting parameters should be monitored carefully in the mother. if abnormal in the mother, then these parameters should also be monitored in the neonate. patients taking valproate may develop hepatic failure [see boxed warning and warnings and precautions (5.1)] . fatal cases of hepatic failure in infants exposed to valproate in utero have also been reported following maternal use of valproate during pregnancy. hypoglycemia has been reported in neonates whose mothers have taken valproate during pregnancy. data human neural tube defects and other structural abnormalities there is an extensive body of evidence demonstrating that exposure to valproate in utero increases the risk of neural tube defects and other structural abnormalities. based on published data from the cdc's national birth defects prevention network, the risk of spina bifida in the general population is about 0.06 to 0.07% (6 to 7 in 10,000 births) compared to the risk following in utero valproate exposure estimated to be approximately 1 to 2% (100 to 200 in 10,000 births). the naaed pregnancy registry has reported a major malformation rate of 9 to 11% in the offspring of women exposed to an average of 1,000 mg/day of valproate monotherapy during pregnancy. these data show an up to a five-fold increased risk for any major malformation following valproate exposure in utero compared to the risk following exposure in utero to other aeds taken as monotherapy. the major congenital malformations included cases of neural tube defects, cardiovascular malformations, craniofacial defects (e.g., oral clefts, craniosynostosis), hypospadias, limb malformations (e.g., clubfoot, polydactyly), and other malformations of varying severity involving other body systems [see warnings and precautions (5.2)] . effect on iq and neurodevelopmental effects published epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores than children exposed to either another aed in utero or to no aeds in utero . the largest of these studies1 is a prospective cohort study conducted in the united states and united kingdom that found that children with prenatal exposure to valproate (n=62) had lower iq scores at age 6 (97 [95% c.i. 94 to 101]) than children with prenatal exposure to the other anti-epileptic drug monotherapy treatments evaluated: lamotrigine (108 [95% c.i. 105 to 110]), carbamazepine (105 [95% c.i. 102 to 108]) and phenytoin (108 [95% c.i. 104 to 112]). it is not known when during pregnancy cognitive effects in valproate-exposed children occur. because the women in this study were exposed to aeds throughout pregnancy, whether the risk for decreased iq was related to a particular time period during pregnancy could not be assessed [see warnings and precautions (5.3)] . although the available studies have methodological limitations, the weight of the evidence supports a causal association between valproate exposure in utero and subsequent adverse effects on neurodevelopment, including increases in autism spectrum disorders and attention deficit/hyperactivity disorder (adhd). an observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders. in this study, children born to mothers who had used valproate products during pregnancy had 2.9 times the risk (95% confidence interval [ci]: 1.7 to 4.9) of developing autism spectrum disorders compared to children born to mothers not exposed to valproate products during pregnancy. the absolute risks for autism spectrum disorders were 4.4% (95% ci: 2.6% to 7.5%) in valproate-exposed children and 1.5% (95% ci: 1.5% to 1.6%) in children not exposed to valproate products. another observational study found that children who were exposed to valproate in utero had an increased risk of adhd (adjusted hr 1.48; 95% ci, 1.09 to 2.00) compared with the unexposed children. because these studies were observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder and adhd cannot be considered definitive. other there are published case reports of fatal hepatic failure in offspring of women who used valproate during pregnancy. animal in developmental toxicity studies conducted in mice, rats, rabbits, and monkeys, increased rates of fetal structural abnormalities, intrauterine growth retardation, and embryo-fetal death occurred following administration of valproate to pregnant animals during organogenesis at clinically relevant doses (calculated on a body surface area [mg/m2 ] basis). valproate induced malformations of multiple organ systems, including skeletal, cardiac, and urogenital defects. in mice, in addition to other malformations, fetal neural tube defects have been reported following valproate administration during critical periods of organogenesis, and the teratogenic response correlated with peak maternal drug levels. behavioral abnormalities (including cognitive, locomotor, and social interaction deficits) and brain histopathological changes have also been reported in mice and rat offspring exposed prenatally to clinically relevant doses of valproate. risk summary valproate is excreted in human milk. data in the published literature describe the presence of valproate in human milk (range: 0.4 mcg/ml to 3.9 mcg/ml), corresponding to 1% to 10% of maternal serum levels. valproate serum concentrations collected from breastfed infants aged 3 days postnatal to 12 weeks following delivery ranged from 0.7 mcg/ml to 4 mcg/ml, which were 1% to 6% of maternal serum valproate levels. a published study in children up to six years of age did not report adverse developmental or cognitive effects following exposure to valproate via breast milk [see data (human)] . there are no data to assess the effects of divalproex sodium on milk production or excretion. clinical considerations the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for divalproex sodium and any potential adverse effects on the breastfed infant from divalproex sodium or from the underlying maternal condition. monitor the breastfed infant for signs of liver damage including jaundice and unusual bruising or bleeding. there have been reports of hepatic failure and clotting abnormalities in offspring of women who used valproate during pregnancy [see use in specific populations (8.1)] . data human in a published study, breast milk and maternal blood samples were obtained from 11 epilepsy patients taking valproate at doses ranging from 300 mg/day to 2,400 mg/day on postnatal days 3 to 6. in 4 patients who were taking valproate only, breast milk contained an average valproate concentration of 1.8 mcg/ml (range: 1.1 mcg/ml to 2.2 mcg/ml), which corresponded to 4.8% of the maternal plasma concentration (range: 2.7% to 7.4%). across all patients (7 of whom were taking other aeds concomitantly), similar results were obtained for breast milk concentration (1.8 mcg/ml, range: 0.4 mcg/ml to 3.9 mcg/ml) and maternal plasma ratio (5.1%, range: 1.3% to 9.6%). a published study of 6 breastfeeding mother-infant pairs measured serum valproate levels during maternal treatment for bipolar disorder (750 mg/day or 1,000 mg/day). none of the mothers received valproate during pregnancy, and infants were aged from 4 weeks to 19 weeks at the time of evaluation. infant serum levels ranged from 0.7 mcg/ml to 1.5 mcg/ml. with maternal serum valproate levels near or within the therapeutic range, infant exposure was 0.9% to 2.3% of maternal levels. similarly, in 2 published case reports with maternal doses of 500 mg/day or 750 mg/day during breastfeeding of infants aged 3 months and 1 month, infant exposure was 1.5% and 6% that of the mother, respectively. a prospective observational multicenter study evaluated the long-term neurodevelopmental effects of aed use on children. pregnant women receiving monotherapy for epilepsy were enrolled with assessments of their children at ages 3 years and 6 years. mothers continued aed therapy during the breastfeeding period. adjusted iqs measured at 3 years for breastfed and non-breastfed children were 93 (n=11) and 90 (n=24), respectively. at 6 years, the scores for breastfed and non-breastfed children were 106 (n=11) and 94 (n=25), respectively (p=0.04). for other cognitive domains evaluated at 6 years, no adverse cognitive effects of continued exposure to an aed (including valproate) via breast milk were observed. contraception women of childbearing potential should use effective contraception while taking valproate [see boxed warning, warnings and precautions (5.4), drug interactions (7), and use in specific populations (8.1)] . this is especially important when valproate use is considered for a condition not usually associated with permanent injury or death such as prophylaxis of migraine headaches [see contraindications (4)] . infertility there have been reports of male infertility coincident with valproate therapy [see adverse reactions (6.2)] . in animal studies, oral administration of valproate at clinically relevant doses resulted in adverse reproductive effects in males [see nonclinical toxicology (13.1)] . experience has indicated that pediatric patients under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions [see boxed warning and warnings and precautions (5.1)] . when divalproex sodium delayed-release capsules are used in this patient group, it should be used with extreme caution and as a sole agent. the benefits of therapy should be weighed against the risks. above the age of 2 years, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. younger children, especially those receiving enzyme inducing drugs, will require larger maintenance doses to attain targeted total and unbound valproate concentrations. pediatric patients (i.e., between 3 months and 10 years) have 50% higher clearances expressed on weight (i.e., ml/min/kg) than do adults. over the age of 10 years, children have pharmacokinetic parameters that approximate those of adults. the variability in free fraction limits the clinical usefulness of monitoring total serum valproic acid concentrations. interpretation of valproic acid concentrations in children should include consideration of factors that affect hepatic metabolism and protein binding. pediatric clinical trials divalproex sodium was studied in seven pediatric clinical trials. two of the pediatric studies were double-blinded placebo-controlled trials to evaluate the efficacy of divalproex sodium extended-release tablets for the indications of mania (150 patients aged 10 to 17 years, 76 of whom were on divalproex sodium extended-release tablets) and migraine (304 patients aged 12 to 17 years, 231 of whom were on divalproex sodium extended-release tablets). efficacy was not established for either the treatment of migraine or the treatment of mania. the most common drug-related adverse reactions (reported > 5% and twice the rate of placebo) reported in the controlled pediatric mania study were nausea, upper abdominal pain, somnolence, increased ammonia, gastritis and rash. the remaining five trials were long term safety studies. two six-month pediatric studies were conducted to evaluate the long-term safety of divalproex sodium extended-release tablets for the indication of mania (292 patients aged 10 to 17 years). two twelve-month pediatric studies were conducted to evaluate the long-term safety of divalproex sodium extended-release tablets for the indication of migraine (353 patients aged 12 to 17 years). one twelve-month study was conducted to evaluate the safety of divalproex sodium delayed-release capsules in the indication of partial seizures (169 patients aged 3 to 10 years). in these seven clinical trials, the safety and tolerability of divalproex sodium in pediatric patients were shown to be comparable to those in adults [see adverse reactions (6)] . juvenile animal toxicology in studies of valproate in immature animals, toxic effects not observed in adult animals included retinal dysplasia in rats treated during the neonatal period (from postnatal day 4) and nephrotoxicity in rats treated during the neonatal and juvenile (from postnatal day 14) periods. the no-effect dose for these findings was less than the maximum recommended human dose on a mg/m2 basis. no patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. in a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. a higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. discontinuation of valproate was occasionally associated with the latter two events. it is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients. a study of elderly patients with dementia revealed drug related somnolence and discontinuation for somnolence [see warnings and precautions (5.14)] . the starting dose should be reduced in these patients, and dosage reductions or discontinuation should be considered in patients with excessive somnolence [see dosage and administration (2.2)] . the capacity of elderly patients (age range: 68 to 89 years) to eliminate valproate has been shown to be reduced compared to younger adults (age range: 22 to 26 years) [see clinical pharmacology (12.3)] . liver disease liver disease impairs the capacity to eliminate valproate [see boxed warning, contraindications (4), warnings and precautions (5.1), and clinical pharmacology (12.3)] .

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

aurobindo pharma limited - prasugrel hydrochloride (unii: g89jq59i13) (prasugrel - unii:34k66tbt99) - prasugrel 5 mg - prasugrel tablets are indicated to reduce the rate of thrombotic cv events (including stent thrombosis) in patients with acute coronary syndrome (acs) who are to be managed with percutaneous coronary intervention (pci) as follows: - patients with unstable angina (ua) or non-st-elevation myocardial infarction (nstemi). - patients with st-elevation myocardial infarction (stemi) when managed with primary or delayed pci. prasugrel tablets have been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (mi), or nonfatal stroke compared to clopidogrel. the difference between treatments was driven predominantly by mi, with no difference on strokes and little difference on cv death [see clinical studies (14) ] . prasugrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage (ich) [see warnings and precautions (5.1) and adverse reactions (6.1)] . prasugrel tablets are contraindicated in patients with a history of prior transient ischemic attack (tia) or stroke. in triton-timi 38 (tr ial to assess i mprovement in t herapeutic outcomes by o ptimizing platelet inhibition with prasugrel), patients with a history of tia or ischemic stroke (>3 months prior to enrollment) had a higher rate of stroke on prasugrel tablets (6.5%; of which 4.2% were thrombotic stroke and 2.3% were intracranial hemorrhage [ich]) than on clopidogrel (1.2%; all thrombotic). in patients without such a history, the incidence of stroke was 0.9% (0.2% ich) and 1.0% (0.3% ich) with prasugrel tablets and clopidogrel, respectively. patients with a history of ischemic stroke within 3 months of screening and patients with a history of hemorrhagic stroke at any time were excluded from triton-timi 38. patients who experience a stroke or tia while on prasugrel tablets generally should have therapy discontinued [see adverse reactions (6.1) and clinical studies (14)] . prasugrel tablets are contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to prasugrel or any component of the product [see adverse reactions (6.2)] . risk summary there are no data with prasugrel use in pregnant women to inform a drug-associated risk. no structural malformations were observed in animal reproductive and developmental toxicology studies when rats and rabbits were administered prasugrel during organogenesis at doses of up to 30 times the recommended therapeutic exposures in humans [see data] . due to the mechanism of action of prasugrel, and the associated identified risk of bleeding, consider the benefits and risks of prasugrel and possible risks to the fetus when prescribing prasugrel to a pregnant woman [see boxed warning and warnings and precautions (5.1, 5.3)]. the background risk of major birth defects and miscarriage for the indicated population is unknown. the background risk in the u.s. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. data animal data in embryo-fetal developmental toxicology studies, pregnant rats and rabbits received prasugrel at maternally toxic oral doses equivalent to more than 40 times the human exposure. a slight decrease in fetal body weight was observed, but there were no structural malformations in either species. in prenatal and postnatal rat studies, maternal treatment with prasugrel had no effect on the behavioral or reproductive development of the offspring at doses greater than 150 times the human exposure. risk summary there is no information regarding the presence of prasugrel in human milk, the effects on the breastfed infant, or the effects on milk production. metabolites of prasugrel were found in rat milk [see data] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for prasugrel and any potential adverse effects on the breastfed child from prasugrel or from the underlying maternal condition. data animal data following a 5 mg/kg oral dose of [14 c]-prasugrel to lactating rats, metabolites of prasugrel were detected in the maternal milk and blood. safety and effectiveness in pediatric patients have not been established. in a randomized, placebo-controlled trial, the primary objective of reducing the rate of vaso-occlusive crisis (painful crisis or acute chest syndrome) in pediatric patients, aged 2 to less than 18 years, with sickle cell anemia was not met. in triton-timi 38, 38.5% of patients were ≥65 years of age and 13.2% were ≥75 years of age. the risk of bleeding increased with advancing age in both treatment groups, although the relative risk of bleeding (prasugrel compared with clopidogrel) was similar across age groups. patients ≥75 years of age who received prasugrel 10 mg had an increased risk of fatal bleeding events (1.0%) compared to patients who received clopidogrel (0.1%). in patients ≥75 years of age, symptomatic intracranial hemorrhage occurred in 7 patients (0.8%) who received prasugrel and in 3 patients (0.3%) who received clopidogrel. because of the risk of bleeding, and because effectiveness is uncertain in patients ≥75 years of age [see clinical studies (14)] , use of prasugrel is generally not recommended in these patients, except in high-risk situations (diabetes and past history of myocardial infarction) where its effect appears to be greater and its use may be considered [see warnings and precautions (5.1), clinical pharmacology (12.3), and clinical studies (14)] . in triton-timi 38, 4.6% of patients treated with prasugrel had body weight <60 kg. individuals with body weight <60 kg had an increased risk of bleeding and an increased exposure to the active metabolite of prasugrel [see dosage and administration (2), warnings and precautions (5.1), and clinical pharmacology (12.3)] . consider lowering the maintenance dose to 5 mg in patients <60 kg. the effectiveness and safety of the 5 mg dose have not been prospectively studied [see dosage and administration (2) and clinical pharmacology (12.3)] . no dosage adjustment is necessary for patients with renal impairment. there is limited experience in patients with end-stage renal disease, but such patients are generally at higher risk of bleeding [see warnings and precautions (5.1) and clinical pharmacology (12.3)] . no dosage adjustment is necessary in patients with mild to moderate hepatic impairment (child-pugh class a and b). the pharmacokinetics and pharmacodynamics of prasugrel in patients with severe hepatic disease have not been studied, but such patients are generally at higher risk of bleeding [see warnings and precautions (5.1) and clinical pharmacology (12.3)] . in healthy subjects, patients with stable atherosclerosis, and patients with acs receiving prasugrel, there was no relevant effect of genetic variation in cyp2b6, cyp2c9, cyp2c19, or cyp3a5 on the pharmacokinetics of prasugrel’s active metabolite or its inhibition of platelet aggregation.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

dr.reddy's laboratories inc. - fluoxetine hydrochloride (unii: i9w7n6b1kj) (fluoxetine - unii:01k63sup8d) - fluoxetine tablets are indicated for the acute and maintenance treatment of major depressive disorder in adult patients and in pediatric patients aged 8 to18 years [see clinical studies (14.1) ].   the usefulness of the drug in adult and pediatric patients receiving fluoxetine for extended periods should periodically be re-evaluated [see dosage and administration (2.1) ].   fluoxetine tablets are indicated for the acute and maintenance treatment of obsessions and compulsions in adult patients and in pediatric patients aged 7 to 17 years with obsessive compulsive disorder (ocd) [see clinical studies (14.2) ].   the effectiveness of fluoxetine tablets in long-term use, i.e., for more than 13 weeks, has not been systematically evaluated in placebo-controlled trials. therefore, the physician who elects to use fluoxetine tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see dosage and administration (2.2) ]. fluoxetine tablets are indicate

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

avkare - zolpidem tartrate (unii: wy6w63843k) (zolpidem - unii:7k383oqi23) - zolpidem tartrate tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. zolpidem tartrate tablets have been shown to decrease sleep latency for up to 35 days in controlled clinical studies [see clinical studies (14)]. the clinical trials performed in support of efficacy were 4 to 5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment. zolpidem tartrate is contraindicated in patients with known hypersensitivity to zolpidem. observed reactions include anaphylaxis and angioedema [see warnings and precautions (5.3)]. risk summary neonates born to mothers using zolpidem late in the third trimester of pregnancy have been reported to experience symptoms of respiratory depression and sedation [see clinical considerations and data] . published data on the use of zolpidem during pregnancy have not reported a clear association with zolpidem and major birth defects [see data]. oral administration of zolpidem to pregnant rats and rabbits did not indicate a risk for adverse effects on fetal development at clinically relevant doses [see data]. the estimated background risk 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 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 fetal/neonatal adverse reactions zolpidem crosses the placenta and may produce respiratory depression and sedation in neonates. monitor neonates exposed to zolpidem tartrate tablets during pregnancy and labor for signs of excess sedation, hypotonia, and respiratory depression and manage accordingly. data human data published data from observational studies, birth registries, and case reports on the use of zolpidem during pregnancy do not report a clear association with zolpidem and major birth defects. there are limited postmarketing reports of severe to moderate cases of respiratory depression that occurred after birth in neonates whose mothers had taken zolpidem during pregnancy. these cases required artificial ventilation or intratracheal intubation. the majority of neonates recovered within hours to a few weeks after birth once treated. zolpidem has been shown to cross the placenta. animal data oral administration of zolpidem to pregnant rats during the period of organogenesis at 4, 20, and 100 mg base/kg/day, which are approximately 5, 25, and 120 times the maximum recommended human dose (mrhd) of 10 mg/day (8 mg zolpidem base) based on mg/m 2 body surface area, caused delayed fetal development (incomplete fetal skeletal ossification) at maternally toxic (ataxia) doses 25 and 120 times the mrhd based on mg/m 2 body surface area. oral administration of zolpidem to pregnant rabbits during the period of organogenesis at 1, 4, and 16 mg base/kg/day, which are approximately 2.5, 10, and 40 times the mrhd of 10 mg/day (8 mg zolpidem base) based on mg/m 2 body surface area caused embryo-fetal death and delayed fetal development (incomplete fetal skeletal ossification) at a maternally toxic (decreased body weight gain) dose 40 times the mrhd based on mg/m 2 body surface area. oral administration of zolpidem to pregnant rats from day 15 of gestation through lactation at 4, 20, and 100 mg base/kg/day, which are approximately 5, 25, and 120 times the mrhd of 10 mg/day (8 mg zolpidem base) based on mg/m 2 body surface area, delayed offspring growth and decreased survival at doses 25 and 120 times, respectively, the mrhd based on mg/m 2 body surface area. risk summary limited data from published literature report the presence of zolpidem in human milk. there are reports of excess sedation in infants exposed to zolpidem through breastmilk [see clinical considerations]. there is no information on the effects of zolpidem on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for zolpidem tartrate tablets and any potential adverse effects on the breastfed infant from zolpidem tartrate tablets or from the underlying maternal condition. clinical considerations infants exposed to zolpidem tartrate tablets through breastmilk should be monitored for excess sedation, hypotonia, and respiratory depression. a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 23 hours (approximately 5 elimination half-lives) after zolpidem tartrate tablets administration in order to minimize drug exposure to a breast fed infant. zolpidem tartrate is not recommended for use in children. safety and effectiveness of zolpidem in pediatric patients below the age of 18 years have not been established. in an 8-week study, in pediatric patients (aged 6 to 17 years) with insomnia associated with attention-deficit/hyperactivity disorder (adhd) an oral solution of zolpidem tartrate dosed at 0.25 mg/kg at bedtime did not decrease sleep latency compared to placebo. psychiatric and nervous system disorders comprised the most frequent (> 5%) treatment emergent adverse reactions observed with zolpidem versus placebo and included dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%), and hallucinations were reported in 7% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations [see warnings and precautions (5.4)] . ten patients on zolpidem (7.4%) discontinued treatment due to an adverse reaction. a total of 154 patients in u.s. controlled clinical trials and 897 patients in non-u.s. clinical trials who received zolpidem were ≥ 60 years of age. for a pool of u.s. patients receiving zolpidem at doses of ≤ 10 mg or placebo, there were three adverse reactions occurring at an incidence of at least 3% for zolpidem and for which the zolpidem incidence was at least twice the placebo incidence (i.e., they could be considered drug related). dizziness 3% 0% drowsiness 5% 2% diarrhea 3% 1% a total of 30/1,959 (1.5%) non-u.s. patients receiving zolpidem reported falls, including 28/30 (93%) who were ≥ 70 years of age. of these 28 patients, 23 (82%) were receiving zolpidem doses > 10 mg. a total of 24/1,959 (1.2%) non-u.s. patients receiving zolpidem reported confusion, including 18/24 (75%) who were ≥ 70 years of age. of these 18 patients, 14 (78%) were receiving zolpidem doses > 10 mg. the dose of zolpidem tartrate in elderly patients is 5 mg to minimize adverse effects related to impaired motor and/or cognitive performance and unusual sensitivity to sedative/hypnotic drugs [see warnings and precautions (5.1)]. women clear zolpidem tartrate from the body at a lower rate than men. c max and auc parameters of zolpidem were approximately 45% higher at the same dose in female subjects compared with male subjects. given the higher blood levels of zolpidem tartrate in women compared to men at a given dose, the recommended initial dose of zolpidem tartrate for adult women is 5 mg, and the recommended dose for adult men is 5 or 10 mg. in geriatric patients, clearance of zolpidem is similar in men and women. the recommended dose of zolpidem tartrate in geriatric patients is 5 mg regardless of gender. the recommended dose of zolpidem tartrate in patients with mild to moderate hepatic impairment is 5 mg once daily immediately before bedtime. avoid zolpidem tartrate use in patients with severe hepatic impairment as it may contribute to encephalopathy [see dosage and administration (2.2), warnings and precautions (5.7), clinical pharmacology (12.3)]. zolpidem tartrate is classified as a schedule iv controlled substance by federal regulation. abuse and addiction are separate and distinct from physical dependence and tolerance. abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug effects over time. tolerance may occur to both desired and undesired effects of drugs and may develop at different rates for different effects. addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. it is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. drug addiction is a treatable disease, using a multidisciplinary approach, but relapse is common. studies of abuse potential in former drug abusers found that the effects of single doses of zolpidem tartrate 40 mg were similar, but not identical, to diazepam 20 mg, while zolpidem tartrate 10 mg was difficult to distinguish from placebo. because persons with a history of addiction to, or abuse of, drugs or alcohol are at increased risk for misuse, abuse and addiction of zolpidem, they should be monitored carefully when receiving zolpidem or any other hypnotic. physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. these reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. the following adverse events which are considered to meet the dsm-iii-r criteria for uncomplicated sedative/hypnotic withdrawal were reported during u.s. clinical trials following placebo substitution occurring within 48 hours following last zolpidem treatment: fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic attack, nervousness, and abdominal discomfort. these reported adverse events occurred at an incidence of 1% or less. however, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. postmarketing reports of abuse, dependence and withdrawal have been received.

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

zydus pharmaceuticals (usa) inc. - indomethacin (unii: xxe1cet956) (indomethacin - unii:xxe1cet956) - indomethacin capsules are indicated for: - moderate to severe rheumatoid arthritis including acute flares of chronic disease - moderate to severe ankylosing spondylitis - moderate to severe osteoarthritis - acute painful shoulder (bursitis and/or tendinitis) - acute gouty arthritis indomethacin capsules are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to indomethacin or any components of the drug product [see warnings and precautions (5.7,5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7,5.8) ] - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.1) ] risk summary use of nsaids, including indomethacin capsules, during the third trimester of pregnancy increases the

संयुक्त राज्य - अंग्रेज़ी - NLM (National Library of Medicine)

alembic pharmaceuticals inc. - pregabalin (unii: 55jg375s6m) (pregabalin - unii:55jg375s6m) - pregabalin capsule is indicated for: • management of neuropathic pain associated with diabetic peripheral neuropathy • management of postherpetic neuralgia • adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older • management of fibromyalgia • management of neuropathic pain associated with spinal cord injury  pregabalin is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see warnings and precautions (5.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin during pregnancy. to provide information regarding the effects of in utero exposure to pregabalin, physicians are advised to recommend that pregnant patients taking pregabalin enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. information on the registry can also be found at the website http://www.aedpregnancyregistry.org/ . risk summary observational studies on the use of pregabalin during pregnancy suggest a possible small increase in the rate of overall major birth defects, but there was no consistent or specific pattern of major birth defects identified (see data). available postmarketing data on miscarriage and other maternal, fetal, and long term developmental adverse effects were insufficient to identify risk associated with pregabalin. in animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (auc) greater than or equal to 16 times human exposure at the maximum recommended dose (mrd) of 600 mg/day (see data) . in an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation. the no-effect dose for developmental toxicity was approximately twice the human exposure at mrd. the background risk of major birth defects and miscarriage for the indicated populations are unknown. however, the background risk in the u.s. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. advise pregnant women of the potential risk to a fetus. data human data one database study, which included over 2,700 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 3,063,251 pregnancies unexposed to antiepileptics demonstrated prevalence ratios for major malformations overall of 1.14 (ci 95% 0.96 to 1.35) for pregabalin, 1.29 (ci 95% 1.01 to 1.65) for lamotrigine, 1.39 (ci 95% 1.07 to 1.82) for duloxetine, and 1.24 (ci 95% 1 to 1.54) for exposure to either lamotrigine or duloxetine. important study limitations include uncertainty of whether women who filled a prescription took the medication and inability to adequately control for the underlying disease and other potential confounders. a published study included results from two separate databases. one database, which included 353 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 368,489 pregnancies unexposed to antiepileptics, showed no increase in risk of major birth defects; adjusted relative risk 0.87 (ci 95% 0.53 to 1.42). the second database, which included 118 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 380,347 pregnancies unexposed to antiepileptics, suggested a small increase in risk of major birth defects; adjusted relative risk 1.26 (ci 95% 0.64 to 2.49). the risk estimates crossed the null, and the study had limitations similar to the prior study. other published epidemiologic studies reported inconsistent findings. no specific pattern of birth defects was identified across studies. all of the studies had limitations due to their retrospective design. animal data when pregnant rats were given pregabalin (500, 1250, or 2500 mg/kg) orally throughout the period of organogenesis, incidences of specific skull alterations attributed to abnormally advanced ossification (premature fusion of the jugal and nasal sutures) were increased at greater than or equal to 1250 mg/kg, and incidences of skeletal variations and retarded ossification were increased at all doses. fetal body weights were decreased at the highest dose. the low dose in this study was associated with a plasma exposure (auc) approximately 17 times human exposure at the mrd of 600 mg/day. a no-effect dose for rat embryo-fetal developmental toxicity was not established. when pregnant rabbits were given pregabalin (250, 500, or 1250 mg/kg) orally throughout the period of organogenesis, decreased fetal body weight and increased incidences of skeletal malformations, visceral variations, and retarded ossification were observed at the highest dose. the no-effect dose for developmental toxicity in rabbits (500 mg/kg) was associated with a plasma exposure approximately 16 times human exposure at the mrd. in a study in which female rats were dosed with pregabalin (50, 100, 250, 1250, or 2500 mg/kg) throughout gestation and lactation, offspring growth was reduced at greater than or equal to 100 mg/kg and offspring survival was decreased at greater than or equal to 250 mg/kg. the effect on offspring survival was pronounced at doses greater than or equal to 1250 mg/kg, with 100% mortality in high-dose litters. when offspring were tested as adults, neurobehavioral abnormalities (decreased auditory startle responding) were observed at greater than or equal to 250 mg/kg and reproductive impairment (decreased fertility and litter size) was seen at 1250 mg/kg. the no-effect dose for pre- and postnatal developmental toxicity in rats (50 mg/kg) produced a plasma exposure approximately 2 times human exposure at the mrd. in the prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures greater than or equal to 50 times the mean human exposure (auc (0-24) of 123 µg∙hr/ml) at the mrd. risk summary small amounts of pregabalin have been detected in the milk of lactating women. a pharmacokinetic study in lactating women detected pregabalin in breast milk at average steady state concentrations approximately 76% of those in maternal plasma. the estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 ml/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose (see data) . the study did not evaluate the effects of pregabalin on milk production or the effects of pregabalin on the breastfed infant. based on animal studies, there is a potential risk of tumorigenicity with pregabalin exposure via breast milk to the breastfed infant [see nonclinical toxicology (13.1)] . available clinical study data in patients greater than 12 years of age do not provide a clear conclusion about the potential risk of tumorigenicity with pregabalin [see warnings and precautions (5.9)] . because of the potential risk of tumorigenicity, breastfeeding is not recommended during treatment with pregabalin. data a pharmacokinetic study in ten lactating women, who were at least 12 weeks postpartum, evaluated the concentrations of pregabalin in plasma and breast milk. pregabalin 150 mg oral capsule was given every 12 hours (300 mg daily dose) for a total of four doses. pregabalin was detected in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. the estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 ml/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose. the study did not evaluate the effects of pregabalin on milk production. infants did not receive breast milk obtained during the dosing period, therefore, the effects of pregabalin on the breast fed infant were not evaluated. infertility males effects on spermatogenesis in a randomized, double-blind, placebo-controlled non-inferiority study to assess the effect of pregabalin on sperm characteristics, healthy male subjects received pregabalin at a daily dose up to 600 mg (n=111) or placebo (n=109) for 13 weeks (one complete sperm cycle) followed by a 13-week washout period (off-drug). a total of 65 subjects in the pregabalin group (59%) and 62 subjects in the placebo group (57%) were included in the per protocol (pp) population. these subjects took study drug for at least 8 weeks, had appropriate timing of semen collections and did not have any significant protocol violations. among these subjects, approximately 9% of the pregabalin group (6/65) vs. 3% in the placebo group (2/62) had greater than or equal to 50% reduction in mean sperm concentrations from baseline at week 26 (the primary endpoint). the difference between pregabalin and placebo was within the pre-specified non-inferiority margin of 20%. there were no adverse effects of pregabalin on sperm morphology, sperm motility, serum fsh or serum testosterone levels as compared to placebo. in subjects in the pp population with greater than or equal to 50% reduction in sperm concentration from baseline, sperm concentrations were no longer reduced by greater than or equal to 50% in any affected subject after an additional 3 months off-drug. in one subject, however, subsequent semen analyses demonstrated reductions from baseline of greater than or equal to 50% at 9 and 12 months off-drug. the clinical relevance of these data is unknown. in the animal fertility study with pregabalin in male rats, adverse reproductive and developmental effects were observed [see nonclinical toxicology (13.1)]. neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and neuropathic pain associated with spinal cord injury safety and effectiveness in pediatric patients have not been established. fibromyalgia safety and effectiveness in pediatric patients have not been established. a 15-week, placebo-controlled trial was conducted with 107 pediatric patients with fibromyalgia, ages 12 through 17 years, at pregabalin total daily doses of 75 to 450 mg per day. the primary efficacy endpoint of change from baseline to week 15 in mean pain intensity (derived from an 11-point numeric rating scale) showed numerically greater improvement for the pregabalin-treated patients compared to placebo-treated patients, but did not reach statistical significance. the most frequently observed adverse reactions in the clinical trial included dizziness, nausea, headache, weight increased, and fatigue. the overall safety profile in adolescents was similar to that observed in adults with fibromyalgia. adjunctive therapy for partial-onset seizures safety and effectiveness in pediatric patients below the age of 1 month have not been established. 4 to less than 17 years of age with partial-onset seizures the safety and effectiveness of pregabalin as adjunctive treatment for partial-onset seizures in pediatric patients 4 to less than 17 years of age have been established in a 12-week, double-blind, placebo-controlled study (n=295) [see clinical studies (14.3)]. patients treated with pregabalin 10 mg/kg/day had, on average, a 21.0% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0185). patients treated with pregabalin 2.5 mg/kg/day had, on average, a 10.5% greater reduction in partial-onset seizures than patients treated with placebo, but the difference was not statistically significant (p=0.2577). responder rates (50% or greater reduction in partial-onset seizure frequency) were a key secondary efficacy parameter and showed numerical improvement with pregabalin compared with placebo: the responder rates were 40.6%, 29.1%, and 22.6%, for pregabalin 10 mg/kg/day, pregabalin 2.5 mg/kg/day, and placebo, respectively. the most common adverse reactions (≥5%) with pregabalin in this study were somnolence, weight increased, and increased appetite [see adverse reactions (6.1)]. the use of pregabalin 2.5 mg/kg/day in pediatric patients is further supported by evidence from adequate and well-controlled studies in adults with partial-onset seizures and pharmacokinetic data from adult and pediatric patients [see clinical pharmacology (12.3)] . 1 month to less than 4 years of age with partial-onset seizures the safety and effectiveness of pregabalin as adjunctive treatment for partial-onset seizures in pediatric patients 1 month to less than 4 years of age have been established in a 14-day double-blind, placebo-controlled study (n=175) [see clinical studies (14.3)] . the youngest subject evaluated was 3 months of age; use in patients 1 month to less than 3 months of age is supported by additional pharmacokinetic analyses. patients treated with pregabalin 14 mg/kg/day had, on average, 43.9% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0223). in addition, pediatric patients treated with pregabalin 14 mg/kg/day showed numerical improvement in responder rates (≥50% reduction in partial-onset seizure frequency) compared with placebo (53.6% versus 41.5%). patients treated with pregabalin 7 mg/kg/day did not show improvement relative to placebo for either endpoint. the most common dose-related adverse reactions (≥5%) with pregabalin in this study were somnolence, pneumonia, and viral infection [see adverse reactions (6.1)] . juvenile animal data in studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (postnatal day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learning and memory, altered locomotor activity, decreased auditory startle responding and habituation) and reproductive impairment (delayed sexual maturation and decreased fertility in males and females) were observed at doses greater than or equal to 50 mg/kg. the neurobehavioral changes of acoustic startle persisted at greater than or equal to 250 mg/kg and locomotor activity and water maze performance at greater than or equal to 500 mg/kg in animals tested after cessation of dosing and, thus, were considered to represent long-term effects. the low effect dose for developmental neurotoxicity and reproductive impairment in juvenile rats (50 mg/kg) was associated with a plasma pregabalin exposure (auc) approximately equal to human exposure at the maximum recommended dose of 600 mg/day. a no-effect dose was not established. in controlled clinical studies of pregabalin in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older. in controlled clinical studies of pregabalin in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older. in controlled clinical studies of pregabalin in epilepsy, there were only 10 patients 65 to 74 years of age, and 2 patients who were 75 years of age or older. no overall differences in safety and efficacy were observed between these patients and younger patients. in controlled clinical studies of pregabalin in fibromyalgia, 106 patients were 65 years of age or older. although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy. pregabalin is known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin may be greater in patients with impaired renal function. because pregabalin is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment [see dosage and administration (2.7)] . pregabalin is eliminated primarily by renal excretion and dose adjustment is recommended for adult patients with renal impairment [see dosage and administration (2.7) and clinical pharmacology (12.3)]. the use of pregabalin in pediatric patients with compromised renal function has not been studied. pregabalin is a schedule v controlled substance. pregabalin is not known to be active at receptor sites associated with drugs of abuse. as with any cns active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior). in a study of recreational users (n=15) of sedative/hypnotic drugs, including alcohol, pregabalin (450 mg, single dose) received subjective ratings of “good drug effect,” “high” and “liking” to a degree that was similar to diazepam (30 mg, single dose). in controlled clinical studies in over 5500 patients, 4 % of pregabalin-treated patients and 1 % of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1 to 12%. in clinical studies, following abrupt or rapid discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache or diarrhea [see warnings and precautions (5.6)] , consistent with physical dependence. in the postmarketing experience, in addition to these reported symptoms there have also been reported cases of anxiety and hyperhidrosis.