Spojené štáty - angličtina - NLM (National Library of Medicine)

aurobindo pharma limited - nevirapine hemihydrate (unii: b7xf2td73c) (nevirapine - unii:99dk7fvk1h) - nevirapine 50 mg in 5 ml - nevirapine oral suspension is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (hiv-1) infection in adults and pediatric patients 15 days and older [see clinical studies (14.1, 14.2)] . limitations of use: based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine oral suspension is not recommended to be initiated, unless the benefit outweighs the risk, in: - adult females with cd4+ cell counts greater than 250 cells/mm3 or - adult males with cd4+ cell counts greater than 400 cells/mm3 [see warnings and precautions (5.1)]. nevirapine oral suspension is contraindicated: - in patients with moderate or severe (child-pugh class b or c, respectively) hepatic impairment [see warnings and precautions (5.1)  and use in specific populations (8.7) ]. - for use as part of occupational and non-occupational post-exposure prophylaxis (pep) regimens [see warnings and precautions (5.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to nevirapine during pregnancy. healthcare providers are encouraged to register patients by calling the antiretroviral pregnancy registry (apr) at 1-800-258-4263. risk summary available data from the apr show no difference in the risk of overall major birth defects for nevirapine compared with the background rate for major birth defects of 2.7% in the u.s. reference population of the metropolitan atlanta congenital defects program (macdp) [see data] . the rate of miscarriage is not reported in the apr. the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15 to 20%. the background risk of birth defects and miscarriage for the indicated population is unknown. methodological limitations of the apr include the use of macdp as the external comparator group. the macdp population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation. in literature reports, immediate-release nevirapine exposure (cmin ) can be up to 29% lower during pregnancy. however, as this reduction was not found to be clinically meaningful, dose adjustment is not necessary [see data] . there is a risk for severe hepatic events in pregnant women exposed to nevirapine [see clinical considerations] . in animal reproduction studies, no evidence of adverse developmental outcomes was observed following oral administration of nevirapine during organogenesis in the rat and rabbit, at systemic exposures (auc) to nevirapine approximately equal (rats) and 50% higher (rabbits) than the exposure in humans at the recommended 400 mg daily dose [see data] . clinical considerations maternal adverse reactions severe hepatic events, including fatalities, have been reported in pregnant women receiving chronic nevirapine therapy as part of combination treatment of hiv-1 infection. regardless of pregnancy status, women with cd4+ cell counts greater than 250 cells/mm3 should not initiate nevirapine unless the benefit outweighs the risk. it is unclear if pregnancy augments the risk observed in non-pregnant women [see warnings and precautions (5.1)] . data human data based on prospective reports to the apr of exposures to nevirapine during pregnancy resulting in live births (including over 1100 exposed in the first trimester and over 1500 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.0% (95% ci: 2.1%, 4.1%) and 3.3% (95% ci: 2.4%, 4.3%) following first and second/third trimester exposure, respectively, to nevirapine-containing regimens, compared with the background birth defect rate of 2.7% in a u.s. reference population of the macdp. there are several literature reports of chronic administration of immediate-release nevirapine during pregnancy, in which nevirapine pharmacokinetics were compared between pregnancy and postpartum. in these studies, the mean difference in nevirapine cmin during pregnancy as compared to postpartum ranged from no difference to approximately 29% lower. animal data nevirapine was administered orally to pregnant rats (at 0, 12.5, 25, and 50 mg per kg per day) and rabbits (at 0, 30, 100, and 300 mg per kg per day) through organogenesis (on gestation days 7 through 16, and 6 through 18, respectively). no adverse developmental effects were observed at doses producing systemic exposures (auc) approximately equivalent to (rats) or approximately 50% higher (rabbits) than human exposure at the recommended daily dose. in rats, decreased fetal body weights were observed at a maternally toxic dose at an exposure approximately 50% higher than the recommended daily dose. risk summary the centers for disease control and prevention recommend that hiv-1 infected mothers in the united states not breastfeed their infants to avoid risking postnatal transmission of hiv-1 infection. published data report that nevirapine is present in human milk [see data] . there are limited data on the effects of nevirapine on the breastfed infant. there is no information on the effects of nevirapine on milk production. because of the potential for (1) hiv-1 transmission (in hiv-negative infants), (2) developing viral resistance (in hiv-positive infants), and (3) serious adverse reactions in nursing infants, mothers should not breastfeed if they are receiving nevirapine. data based on five publications, immediate-release nevirapine was excreted in breast milk at median concentrations ranging from 4080 to 6795 ng/ml, and the median maternal breast milk to maternal plasma concentration ratio range was 59 to 88%. reported infant nevirapine median plasma concentrations were low, ranging from 734 to 1140 ng/ml. the estimated nevirapine dose of 704 to 682 mcg/kg/day for infants fed exclusively with breast milk was lower than the daily recommended nevirapine dose for infants. published literature indicates that rash and hyperbilirubinemia have been seen in infants exposed to nevirapine through breastmilk. infertility limited human data are insufficient to determine the risk of infertility in humans. based on results from animal fertility studies conducted in rats, nevirapine may reduce fertility in females of reproductive potential. it is not known if these effects on fertility are reversible [see nonclinical toxicology (13.1)] . the safety, pharmacokinetic profile, and virologic and immunologic responses of nevirapine have been evaluated in hiv-1 infected pediatric subjects aged 3 months to 18 years [see adverse reactions (6.1) and clinical studies (14.2)] . the safety and pharmacokinetic profile of nevirapine has been evaluated in hiv-1 infected pediatric subjects aged 15 days to less than 3 months [see adverse reactions (6.1) and clinical studies (14.2)] . the most frequently reported adverse events related to nevirapine in pediatric subjects were similar to those observed in adults, with the exception of granulocytopenia, which was more commonly observed in children receiving both zidovudine and nevirapine [see adverse reactions (6.1)  and clinical studies (14.2) ]. clinical trials of nevirapine did not include sufficient numbers of subjects aged 65 and older to determine whether elderly subjects respond differently from younger subjects. in general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. in subjects with renal impairment (mild, moderate or severe), there were no significant changes in the pharmacokinetics of nevirapine. nevirapine is extensively metabolized by the liver and nevirapine metabolites are extensively eliminated by the kidney. nevirapine metabolites may accumulate in patients receiving dialysis; however, the clinical significance of this accumulation is not known. no adjustment in nevirapine dosing is required in patients with crcl greater than or equal to 20 ml per min. the pharmacokinetics of nevirapine have not been evaluated in patients with crcl less than 20 ml per min. in patients undergoing chronic hemodialysis, an additional 200 mg dose following each dialysis treatment is indicated [see dosage and administration (2.4) and clinical pharmacology (12.3) ] . because increased nevirapine levels and nevirapine accumulation may be observed in patients with serious liver disease, do not administer nevirapine to patients with moderate or severe (child-pugh class b or c, respectively) hepatic impairment [see contraindications (4), warnings and precautions (5.1), and clinical pharmacology (12.3)] .

Spojené štáty - angličtina - NLM (National Library of Medicine)

aurobindo pharma limited - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram 5 mg - escitalopram tablets are indicated for the treatment of: - major depressive disorder (mdd) in adults and pediatric patients 12 years of age and older. - generalized anxiety disorder (gad) in adults. additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. escitalopram tablets is contraindicated in patients: - taking maois with escitalopram tablets or within 14 days of stopping treatment with escitalopram tablets because of an increased risk of serotonin syndrome. the use of escitalopram tablets within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.7), and warnings and precautions (5.2)] . starting escitalopram tablets in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.6), and warnings and precautions (5.2)]. - taking pimozide [see drug interactions (7)]. - with a hypersensitivity to escitalopram or citalopram or any of the inactive ingredients in escitalopram tablets. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clnical-and-research-programs/pregnancyregistry/ antidepressants/ risk summary based on data from published observational studies, exposure to ssris, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see warnings and precautions (5.7) and clinical considerations]. available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage. there are risks of persistent pulmonary hypertension of the newborn (pphn) (see data) and poor neonatal adaptation (see clinical considerations) with exposure to selective serotonin reuptake inhibitors (ssris), including escitalopram oxalate, during pregnancy. there are risks associated with untreated depression in pregnancy (see clinical considerations). in animal reproduction studies, both escitalopram and racemic citalopram have been shown to have adverse effects on embryo/fetal and postnatal development, including fetal structural abnormalities, when administered at doses greater than human therapeutic doses (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal risk and/or embryo/fetal risk women who discontinue antidepressants are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective longitudinal study of 201 pregnant women with a history of major depression, who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. maternal adverse reactions use of escitalopram oxalate in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.7)]. fetal/neonatal adverse reactions neonates exposed to ssris or snris, including escitalopram oxalate, late in third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these features are consistent with either a direct toxic effect of ssris and snris or, possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.2)]. data human data exposure to ssris, particularly later in pregnancy, may increase the risk for pphn. pphn occurs in 1 to 2 per 1000 live births in the general populations and is associated with substantial neonatal morbidity and mortality. animal data in a rat embryo/fetal development study, oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses [approximately ≥ 55 times the maximum recommended human dose (mrhd) of 20 mg/day on a mg/m2 basis]. maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was present at all dose levels. the developmental no-effect dose of 56 mg/kg/day is approximately 27 times the mrhd of 20 mg on a mg/m2 basis. no malformations were observed at any of the doses tested (as high as 73 times the mrhd on a mg/m2 basis). when female rats were treated with escitalopram (6, 12, 24, or 48 mg/kg/day) during pregnancy and through weaning, slightly increased offspring mortality and growth retardation were noted at 48 mg/kg/day which is approximately 23 times the mrhd of 20 mg on a mg/m2 basis. slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) was seen at this dose. slightly increased offspring mortality was also seen at 24 mg/kg/day. the no-effect dose was 12 mg/kg/day which is approximately 6 times the mrhd of 20 mg on a mg/m2 basis. in two rat embryo/fetal development studies, oral administration of racemic citalopram (32, 56, or 112 mg/kg/day) to pregnant animals during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose, which is approximately 18 times the mrhd of 60 mg/day on a mg/m2 basis. this dose was also associated with maternal toxicity (clinical signs, decreased body weight gain). the developmental no-effect dose was 56 mg/kg/day is approximately 9 times the mrhd on a mg/m2 basis. in a rabbit study, no adverse effects on embryo/fetal development were observed at doses of racemic citalopram of up to 16 mg/kg/day, or approximately 5 times the mrhd on a mg/m2 basis. thus, developmental effects of racemic citalopram were observed at a maternally toxic dose in the rat and were not observed in the rabbit. when female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were observed at the highest dose, which is approximately 5 times the mrhd of 60 mg on a mg/m2 basis. the no-effect dose was 12.8 mg/kg/day is approximately 2 times the mrhd on a mg/m2 basis. similar effects on offspring mortality and growth were seen when dams were treated throughout gestation and early lactation at doses ≥ 24 mg/kg/day, approximately 4 times the mrhd on a mg/m2 basis. a no-effect dose was not determined in that study. risk summary data from the published literature report the presence of escitalopram and desmethylescitalopram in human milk (see data) . there are reports of excessive sedation, restlessness, agitation, poor feeding and poor weight gain in infants exposed to escitalopram, through breast milk (see clinical considerations) . there are no data on the effects of escitalopram or its metabolites on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for escitalopram oxalate and any potential adverse effects on the breastfed child from escitalopram oxalate or from the underlying maternal condition. clinical considerations infants exposed to escitalopram oxalate should be monitored for excess sedation, restlessness, agitation, poor feeding and poor weight gain. data   a study of 8 nursing mothers on escitalopram with daily doses of 10 to 20 mg/day showed that exclusively breast-fed infants receive approximately 3.9% of the maternal weight-adjusted dose of escitalopram and 1.7% of the maternal weight-adjusted dose of desmethylcitalopram. major depressive disorder the safety and effectiveness of escitalopram oxalate for the treatment of major depressive disorder have been established in pediatric patients 12 years of age and older. use of escitalopram oxalate for this indication is supported by evidence from adequate and well-controlled studies in adults with additional evidence from an 8-week, flexible-dose, placebo-controlled study that compared escitalopram oxalate 10 mg to 20 mg once daily to placebo in pediatric patients 12 to 17 years of age with major depressive disorder [see clinical studies (14.1)] . the safety of escitalopram oxalate was similar to adult patients with mdd [see adverse reactions (6.1)] . the safety and effectiveness of escitalopram oxalate for the treatment of major depressive disorder have not been established in pediatric patients younger than 12 years of age. in a 24-week, open- label safety study in 118 pediatric patient (aged 7 to 11 years) who had major depressive disorder, the safety findings were consistent with the known safety and tolerability profile for escitalopram oxalate. generalized anxiety disorder the safety and effectiveness of escitalopram oxalate for the treatment of generalized anxiety disorder have not been established in pediatric patients younger than 7 years of age. antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see warnings and precautions (5.1)] . decreased appetite and weight loss have been observed in association with the use of ssris. consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an ssri such as escitalopram oxalate. juvenile animal toxicity data in a juvenile animal study, male and female rats were administered escitalopram at 5, 40, or 80 mg/kg/day by oral gavage from postnatal day (pnd) 21 to pnd 69. a delay in sexual maturation was observed in both males and females at ≥ 40 mg/kg/day with a no observed adverse effect level (noael) of 5 mg/kg/day. this noael was associated with plasma auc levels less than those measured at the maximum recommended dose (mrhd) in pediatrics (20 mg). however, there was no effect on reproductive function. increased motor activity (both ambulatory and fine movements) was observed in females prior to daily dosing at ≥ 40 mg/kg/day (3.5 times the mrhd based on auc levels). a reversible disruption of learning and memory function was observed in males at 80 mg/kg/day with a noael of 40 mg/kg/day, which was associated with an auc level 3.5 times those measured at the mrhd in pediatrics. there was no effect on learning and memory function in treated female rats. additional pediatric use information is approved for abbvie inc.’s lexapro (escitalopram) tablets. however, due to abbvie inc.’s marketing exclusivity rights, this drug product is not labeled with that information. approximately 69 patients (6%) of the 1,144 patients receiving escitalopram in controlled trials of escitalopram oxalate in major depressive disorder and gad were 60 years of age or older [see clinical studies (14.1, 14.2)]. the number of elderly patients in these trials was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram oxalate cannot be ruled out. in two pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in subjects 65 years and older as compared to young subjects and cmax was unchanged [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram oxalate for elderly patients is 10 mg daily [see dosage and administration (2.5)] . ssris, including escitalopram oxalate, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [ see warnings and precautions (5.6)] . of 4,422 patients in clinical studies of racemic citalopram, 1,357 were 60 and over, 1,034 were 65 and over, and 457 were 75 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the geriatric and younger patients, but again, greater sensitivity of some elderly individuals cannot be ruled out. increased citalopram exposure occurs in patients with hepatic impairment [see clinical pharmacology (12.3)] . the recommended dosage of escitalopram oxalate in patients with hepatic impairment is 10 mg daily [see dosage and administration (2.5)] . pharmacokinetics of escitalopram oxalate in patients with a creatinine clearance less than 20 ml/minute has not been evaluated. no dosage adjustment is necessary for patients with mild or moderate renal impairment [see dosage and administration (2.5), clinical pharmacology (12.3)] . physical and psychological dependence  animal studies suggest that the abuse liability of racemic citalopram is low. escitalopram oxalate has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. the premarketing clinical experience with escitalopram oxalate did not reveal any drug-seeking behavior. however, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate escitalopram oxalate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

Spojené štáty - angličtina - 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.

Spojené štáty - angličtina - NLM (National Library of Medicine)

aurobindo pharma limited - zolpidem tartrate (unii: wy6w63843k) (zolpidem - unii:7k383oqi23) - zolpidem tartrate 5 mg - 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 tablets are contraindicated in patients - who have experienced complex sleep behaviors after taking zolpidem tartrate tablets [see warnings and precautions (5.1)]. - with known hypersensitivity to zolpidem. observed reactions include anaphylaxis and angioedema [see warnings and precautions (5.4)] . 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 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/m2 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/m2 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/m2 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/m2 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/m2 body surface area, delayed offspring growth and decreased survival at doses 25 and 120 times, respectively, the mrhd based on mg/m2 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 and any potential adverse effects on the breastfed infant from zolpidem tartrate or from the underlying maternal condition. clinical considerations infants exposed to zolpidem tartrate 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 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 (5.5)] . 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). 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 (5.2)] . women clear zolpidem tartrate from the body at a lower rate than men. cmax 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 (5.8), 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. use of zolpidem tartrate may lead to the development of physical and/or psychological dependence. the risk of dependence increases with dose and duration of treatment. the risk of abuse and dependence is also greater in patients with a history of alcohol or drug abuse. zolpidem tartrate should be used with extreme caution in patients with current or past alcohol or drug abuse 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, convulsions, and delirium. the following adverse events, which are considered to meet the dsm-iii-r criteria for uncomplicated sedative/hypnotic withdrawal, were reported during clinical trials with zolpidem tartrate 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. there have been postmarketing reports of abuse, dependence and withdrawal with zolpidem.

Spojené štáty - angličtina - NLM (National Library of Medicine)

aurobindo pharma limited - mirtazapine (unii: a051q2099q) (mirtazapine - unii:a051q2099q) - mirtazapine 7.5 mg - mirtazapine tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies (14)]. mirtazapine 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 (5.3), drug interactions (7)]. - with a known hypersensitivity to mirtazapine or to any of the excipients in mirtazapine tablets. severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (dress), stevens-johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have been reported following the use of mirtazapine tablets [see warnings and precautions (5.6), adverse reactions (6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. risk summary prolonged experience with mirtazapine in pregnant women, based on published observational studies and postmarketing reports, has not reliably identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there are risks associated with untreated depression in pregnancy (see clinical considerations). in animal reproduction studies, oral administration of mirtazpine to pregnant rats and rabbits during the period of organogenesis revealed no evidence of teratogenic effects up to 20 and 17 times the maximum recommended human dose (mrhd) of 45 mg, respectively, based on mg/m2 body surface area. however, in rats, there was an increase in postimplantation loss at 20 times the mrhd based on mg/m2 body surface area. oral administration of mirtazapine to pregnant rats during pregnancy and lactation resulted in an increase in pup deaths and a decrease in pup birth weights at doses 20 times the mrhd based on mg/m2 body surface area (see data). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. data animal data mirtazapine was administered orally to pregnant rats and rabbits during the period of organogenesis at doses of 2.5, 15, and 100 mg/kg/day and 2.5, 10, and 40 mg/kg/day, respectively, which are up to 20 and 17 times the maximum recommended human dose (mrhd) of 45 mg based on mg/m2 body surface area, respectively. no evidence of teratogenic effects was observed. however, in rats, there was an increase in postimplantation loss in dams treated with mirtazapine at 100 mg/kg/day which is 20 times the mrhd based on mg/m2 body surface area. oral administration of mirtazapine at doses of 2.5, 15, and 100 mg/kg/day to pregnant rats during pregnancy and lactation resulted in an increase in pup deaths during the first 3 days of lactation and a decrease in pup birth weights at 20 times the mrhd based on mg/m2 body surface area. the cause of these deaths is not known. the no effect dose level is 3 times the mrhd based on mg/m2 body surface area. risk summary data from published literature report the presence of mirtazapine in human milk at low levels with relative infant doses for mirtazapine ranging between 0.6 and 2.8% of the maternal weight-adjusted dose (see data) . no adverse effects on the breastfed infant have been reported in most cases of maternal use of mirtazapine. there are no data on the effects of mirtazapine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mirtazapine and any potential adverse effects on the breastfed infant from mirtazapine or from the underlying maternal condition. data in a published pooled analysis of 8 breastfeeding mother-infant pairs, the mean (min, max) total relative infant doses for mirtazapine and its desmethyl metabolite were 1.5% (0.6%, 2.8%) and 0.4% (0.1%, 0.7%) of the maternal weight-adjusted dose (median (min, max) dose of 38 mg (30 mg, 120 mg), respectively). no adverse drug effects were reported for any of the infants. the safety and effectiveness of mirtazapine have not been established in pediatric patients with mdd. two placebo-controlled trials in 258 pediatric patients with mdd have been conducted with mirtazapine, and the data were insufficient to establish the safety and effectiveness of mirtazapine in pediatric patients with mdd. antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see boxed warning and warnings and precautions (5.1)]. in an 8-week-long clinical trial in pediatric patients receiving doses between 15 to 45 mg per day, 49% of mirtazapine-treated patients had a weight gain of at least 7%, compared to 5.7% of placebo-treated patients. the mean increase in weight was 4 kg (2 kg sd) for mirtazapine-treated patients versus 1 kg (2 kg sd) for placebo-treated patients [see warnings and precautions (5.7)]. approximately 190 patients ≥65 years of age participated in clinical studies with mirtazapine. mirtazapine is known to be substantially excreted by the kidney (75%), and the risk of decreased clearance of this drug is greater in patients with impaired renal function. pharmacokinetic studies revealed a decreased clearance of mirtazapine in the elderly [see clinical pharmacology (12.3)]. sedating drugs, including mirtazapine, may cause confusion and over-sedation in the elderly. elderly patients may be at greater risk of developing hyponatremia. caution is indicated when administering mirtazapine to elderly patients [see warnings and precautions (5.12), (5.15) and clinical pharmacology (12.3)] . in general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. the clearance of mirtazapine is reduced in patients with moderate to severe renal or hepatic impairment. consequently, plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in patients without renal or hepatic impairment. dosage decrease may be necessary when administering mirtazapine to patients with moderate to severe renal or hepatic impairment [see warnings and precautions (5.13), use in specific populations (8.5), and clinical pharmacology (12.3)].

Spojené štáty - angličtina - NLM (National Library of Medicine)

aurobindo pharma limited - mirtazapine (unii: a051q2099q) (mirtazapine - unii:a051q2099q) - mirtazapine 15 mg - mirtazapine orally disintegrating tablets are indicated for the treatment of major depressive disorder (mdd) in adults [see clinical studies (14)]. mirtazapine orally disintegrating 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 (5.3), drug interactions (7)]. - with a known hypersensitivity to mirtazapine or to any of the excipients in mirtazapine orally disintegrating tablets. severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (dress), stevens-johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have been reported following the use of mirtazapine orally disintegrating tablets [see warnings and precautions (5.6), adverse reactions (6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. risk summary prolonged experience with mirtazapine in pregnant women, based on published observational studies and postmarketing reports, has not reliably identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there are risks associated with untreated depression in pregnancy (see clinical considerations) . in animal reproduction studies, oral administration of mirtazapine to pregnant rats and rabbits during the period of organogenesis revealed no evidence of teratogenic effects up to 20 and 17 times the maximum recommended human dose (mrhd) of 45 mg, respectively, based on mg/m2 body surface area. however, in rats, there was an increase in postimplantation loss at 20 times the mrhd based on mg/m2 body surface area. oral administration of mirtazapine to pregnant rats during pregnancy and lactation resulted in an increase in pup deaths and a decrease in pup birth weights at doses 20 times the mrhd based on mg/m2 body surface area (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. data animal data mirtazapine was administered orally to pregnant rats and rabbits during the period of organogenesis at doses of 2.5, 15, and 100 mg/kg/day and 2.5, 10, and 40 mg/kg/day, respectively, which are up to 20 and 17 times the maximum recommended human dose (mrhd) of 45 mg based on mg/m2 body surface area, respectively. no evidence of teratogenic effects was observed. however, in rats, there was an increase in postimplantation loss in dams treated with mirtazapine at 100 mg/kg/day which is 20 times the mrhd based on mg/m2 body surface area. oral administration of mirtazapine at doses of 2.5, 15, and 100 mg/kg/day to pregnant rats during pregnancy and lactation resulted in an increase in pup deaths during the first 3 days of lactation and a decrease in pup birth weights at 20 times the mrhd based on mg/m2 body surface area. the cause of these deaths is not known. the no effect dose level is 3 times the mrhd based on mg/m2 body surface area. risk summary data from published literature report the presence of mirtazapine in human milk at low levels with relative infant doses for mirtazapine ranging between 0.6 and 2.8% of the maternal weight-adjusted dose (see data) . no adverse effects on the breastfed infant have been reported in most cases of maternal use of mirtazapine. there are no data on the effects of mirtazapine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mirtazapine and any potential adverse effects on the breastfed infant from mirtazapine or from the underlying maternal condition. data in a published pooled analysis of 8 breastfeeding mother-infant pairs, the mean (min, max) total relative infant doses for mirtazapine and its desmethyl metabolite were 1.5% (0.6%, 2.8%) and 0.4% (0.1%, 0.7%) of the maternal weight-adjusted dose (median (min, max) dose of 38 mg (30 mg, 120 mg), respectively). no adverse drug effects were reported for any of the infants. the safety and effectiveness of mirtazapine orally disintegrating tablets have not been established in pediatric patients with mdd. two placebo-controlled trials in 258 pediatric patients with mdd have been conducted with mirtazapine, and the data were insufficient to establish the safety and effectiveness of mirtazapine orally disintegrating tablets in pediatric patients with mdd. antidepressants increased the risk of suicidal thoughts and behaviors in pediatric patients [see boxed warning and warnings and precautions (5.1)]. in an 8-week-long clinical trial in pediatric patients receiving doses between 15 to 45 mg per day, 49% of mirtazapine-treated patients had a weight gain of at least 7%, compared to 5.7% of placebo-treated patients. the mean increase in weight was 4 kg (2 kg sd) for mirtazapine-treated patients versus 1 kg (2 kg sd) for placebo-treated patients [see warnings and precautions (5.7)]. approximately 190 patients ≥65 years of age participated in clinical studies with mirtazapine. mirtazapine orally disintegrating tablets are known to be substantially excreted by the kidney (75%), and the risk of decreased clearance of this drug is greater in patients with impaired renal function. pharmacokinetic studies revealed a decreased clearance of mirtazapine in the elderly [see clinical pharmacology (12.3)]. sedating drugs, including mirtazapine orally disintegrating tablets, may cause confusion and over-sedation in the elderly. elderly patients may be at greater risk of developing hyponatremia. caution is indicated when administering mirtazapine orally disintegrating tablets to elderly patients [see warnings and precautions (5.12), (5.15) and clinical pharmacology (12.3)] . in general, dose selection for an elderly patient should be conservative, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. the clearance of mirtazapine is reduced in patients with moderate to severe renal or hepatic impairment. consequently, plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in patients without renal or hepatic impairment. dosage decrease may be necessary when administering mirtazapine orally disintegrating tablets to patients with moderate to severe renal or hepatic impairment [see warnings and precautions (5.13), use in specific populations (8.5), and clinical pharmacology (12.3)]. mirtazapine orally disintegrating tablets contain phenylalanine, a component of aspartame. mirtazapine orally disintegrating tablets contain the following amount of phenylalanine: 1.5 mg in 15 mg orally disintegrating tablet, 3 mg in 30 mg orally disintegrating tablet, and 4.5 mg in 45 mg orally disintegrating tablet [see warnings and precautions (5.16)].

Spojené štáty - angličtina - NLM (National Library of Medicine)

aurobindo pharma limited - dalfampridine (unii: bh3b64okl9) (dalfampridine - unii:bh3b64okl9) - dalfampridine extended-release tablets are indicated as a treatment to improve walking in adult patients with multiple sclerosis (ms). this was demonstrated by an increase in walking speed [see clinical studies (14)]. the use of dalfampridine extended-release tablets are contraindicated in the following conditions: - history of seizure [see warnings and precautions (5.1)] - moderate or severe renal impairment (crcl≤50 ml/min) [see warnings and precautions (5.2)] - history of hypersensitivity to dalfampridine extended-release tablets or 4-aminopyridine; reactions have included anaphylaxis [see warnings and precautions (5.4)] risk summary there are no adequate data on the developmental risk associated with use of dalfampridine extended-release tablets in pregnant women. administration of dalfampridine to animals during pregnancy and lactation resulted in decreased offspring viability and growth at clinically relevant doses [see data] . 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. the background risk of major birth defects and miscarriage for the indicated population is unknown. data animal data oral administration of dalfampridine to pregnant rats and rabbits throughout organogenesis resulted in no evidence of developmental toxicity in either species. the highest doses tested (10 mg/kg/day in rats, 5 mg/kg/day in rabbits), which were associated with maternal toxicity, are approximately 5 times the mrhd on a body surface area (mg/m2 ) basis. oral administration of dalfampridine (0, 1, 3, and 9 to 6 mg/kg/day; high dose reduced during the second week of dosing) to female rats throughout pregnancy and lactation resulted in decreased offspring viability at the highest dose tested and decreased body weight in offspring at the mid and high doses. the no-effect dose for pre- and postnatal developmental toxicity in rats (1 mg/kg/day) is less than the mrhd on a mg/m2 basis. risk summary there are no data on the presence of dalfampridine in human milk, the effects of dalfampridine on the breastfed infant, or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dalfampridine and any potential adverse effects on the breastfed infant from dalfampridine or from the underlying maternal condition. safety and effectiveness in patients younger than 18 years of age have not been established. clinical studies of dalfampridine extended-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. a population pk analysis showed that dalfampridine clearance modestly decreased with increasing age, but not sufficiently to necessitate a modification of dose with age. other reported clinical experience has identified no differences in responses between the elderly and younger patients. dalfampridine extended-release tablets are known to be substantially excreted by the kidneys and the risk of adverse reactions, including seizures, is greater with increasing exposure of dalfampridine. because elderly patients are more likely to have decreased renal function, it is particularly important to know the estimated creatinine clearance (crcl) in these patients [see warnings and precautions (5.2)]. clearance of dalfampridine is decreased in patients with renal impairment and is significantly correlated with creatinine clearance (crcl) [see clinical pharmacology (12.3)] . dalfampridine extended-release tablets are contraindicated in patients with moderate or severe renal impairment (crcl ≤50 ml/min) [see contraindications (4)]. the risk of seizures in patients with mild renal impairment (crcl 51 to 80 ml/min) is unknown, but dalfampridine plasma levels in these patients may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures. if unknown, estimated creatinine clearance should be calculated prior to initiating treatment with dalfampridine extended-release tablets [see dosage and administration (2.3) and warnings and precautions (5.2)] .

Tanzánia - angličtina - Tanzania Medicinces & Medical Devices Authority

aurobindo pharma limited, india - telmisartan - uncoated tablets - 20 mg

Tanzánia - angličtina - Tanzania Medicinces & Medical Devices Authority

aurobindo pharma limited, india - telmisartan - uncoated tablets - 80mg

Tanzánia - angličtina - Tanzania Medicinces & Medical Devices Authority

aurobindo pharma limited, india - telmisartan - uncoated tablets - 40 mg