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

contract pharmacy services-pa - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram 10 mg - escitalopram tablets are indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age [ see clinical studies ( 14.1) ]. a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. escitalopram tablets are indicated for the acute treatment of generalized anxiety disorder (gad) in adults [ see clinical studies ( 14.2) ]. generalized anxiety disorder (dsm-iv) is cha

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

xspire pharma, llc - ciprofloxacin hydrochloride (unii: 4ba73m5e37) (ciprofloxacin - unii:5e8k9i0o4u) - ciprofloxacin 0.5 mg in 0.25 ml - ciprofloxacin otic solution is a quinolone antimicrobial indicated for the treatment of acute otitis externa due to susceptible isolates of pseudomonas aeruginosa or staphylococcus aureus . ciprofloxacin otic solution is contraindicated in persons with a history of hypersensitivity to ciprofloxacin. pregnancy category c. reproduction studies have been performed in rats and mice using oral doses of up to 100 mg/kg and intravenous (iv) doses up to 30 mg/kg and have revealed no evidence of harm to the fetus as a result of ciprofloxacin. in rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, but no teratogenicity was observed at either dose. after intravenous administration of doses up to 20 mg/kg, no maternal toxicity was produced in the rabbit, and no embryotoxicity or teratogenicity was observed. animal reproduction studies have not been conducted with ciprofloxacin otic solution. no adequate and well-controlled studies have been performed in pregnant women. caution should be exercised when ciprofloxacin otic solution is used by a pregnant woman. ciprofloxacin is excreted in human milk with systemic use. it is not known whether ciprofloxacin is excreted in human milk following otic use. because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. the safety and effectiveness of ciprofloxacin otic solution in infants below one year of age have not been established. the efficacy of ciprofloxacin otic solution in treating otitis externa in pediatric patients one year or older has been demonstrated in controlled clinical trials (see section 14 clinical studies). there is no evidence that the otic administration of quinolones has any effect on weight bearing joints, even though systemic administration of some quinolones has been shown to cause arthropathy in immature animals. no overall differences in safety and effectiveness have been observed between elderly and younger patients.

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

contract pharmacy services-pa - escitalopram oxalate (unii: 5u85dbw7lo) (escitalopram - unii:4o4s742any) - escitalopram 20 mg - escitalopram tablets, usp are indicated for the acute and maintenance treatment of major depressive disorder in adults and in adolescents 12 to 17 years of age [ see clinical studies (14.1) ]. a major depressive episode (dsm-iv) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation. escitalopram tablets, usp are indicated for the acute treatment of generalized anxiety disorder (gad) in adults [ see   clinical   studies   (14.2) ]. generalized anxiety disorder (dsm-iv) is characteriz

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

astellas pharma us, inc. - isavuconazonium sulfate (unii: 31q44514jv) (isavuconazole - unii:60uto373ke) - isavuconazonium sulfate 186 mg - cresemba® is indicated for the treatment of invasive aspergillosis as follows: cresemba for injection : adults and pediatric patients 1   year of age and older [see clinical studies ( 14.1 ) and clinical pharmacology ( 12.4 )] cresemba capsules : adults and pediatric patients 6 years of age and older who weigh 16 kilograms ( kg ) and greater [see dosage and administration ( 2.3 ) clinical studies ( 14.1 ) and clinical pharmacology ( 12.4 )] cresemba is indicated for the   treatment of invasive mucormycosis as follows: cresemba for injection : adults and pediatric patients 1   year of age and older [see clinical studies ( 14.1 ) and clinical pharmacology ( 12.3 , 12.4 )] cresemba capsules : adults and pediatric patients 6 years of age and older who weigh 16 kg and greater [see dosage and administration ( 2.3 )], clinical studies ( 14.1 ) and clinical pharmacology ( 12.3 ,   12.4 )] specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy. therapy may be instituted before the results of the cultures and other laboratory studies are known. however, once these results become available, antifungal therapy should be adjusted accordingly. risk summary based on findings from animal studies, cresemba may cause fetal harm when administered to a pregnant woman. there are no available human data on the use of cresemba in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies, perinatal mortality was increased in the offspring of pregnant rats dosed orally with isavuconazonium sulfate at approximately 0.5 times the clinical exposure during pregnancy through the weaning period. in animal studies when isavuconazonium chloride was administered by oral gavage to pregnant rats and rabbits during organogenesis at exposures corresponding to less than the human maintenance dose, increases in the incidences of multiple skeletal abnormalities, including rudimentary cervical ribs and fused zygomatic arches, were observed (see data). advise pregnant women of the potential risk to a fetus [see warnings and precautions (5.4)] . 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. data animal data isavuconazonium chloride administration during organogenesis (gestational days 6-17 in rats and gestational days 6-18 in rabbits) was associated with dose-related increases in the incidences of rudimentary cervical ribs in rats and rabbits at 30 and 45 mg/kg, respectively, equivalent to about 0.2 and 0.1 times of the clinical exposure based on auc comparisons. in rats, dose-related increases in the incidences of zygomatic arch fusion and supernumerary ribs/rudimentary supernumerary ribs were also noted at 30 mg/kg and above, equivalent to 0.2 times the human auc. skeletal abnormalities have also been observed in embryo-fetal development studies of other azole antifungal agents. isavuconazonium sulfate increased perinatal mortality in the pups when orally administered to pregnant rats during pregnancy and lactation (gestational day 6 through postpartum day 20) at doses up to 90 mg/kg/day (approximately 0.5 times the clinical exposure based on auc comparison). no effect on the duration of pregnancy or delivery was seen in the pups at this same dose. risk summary there are no data on the presence of isavuconazole in human milk, the effects on the breastfed infant or the effects on milk production. isavuconazole was present in the milk of lactating rats following intravenous administration. when a drug is present in animal milk, it is likely that the drug will be present in human milk. therefore, breastfeeding should be discontinued during treatment with cresemba. contraception cresemba may cause embryo-fetal harm when administered to pregnant women [see warnings and precautions (5.4) and use in specific populations (8.1)]. advise female patients of reproductive potential to use effective contraception during treatment with cresemba and for 28 days after the final dose. invasive aspergillosis the safety and effectiveness of cresemba for injection for the treatment of invasive aspergillosis have been established in pediatric patients 1 year of age and older. the safety and effectiveness of cresemba capsules for the treatment of invasive aspergillosis have been established in pediatric patients 6 year of age and older weighing 16 kg and greater. use of cresemba in this age group for treatment of invasive aspergillosis is supported by evidence from one adequate and well-controlled trial in adult patients and additional pharmacokinetic and safety data in pediatric patients 1 year of age and older [see clinical pharmacology (12.3)]. adverse reactions in this pediatric population were similar to those reported in the adult population [see adverse reactions (6.1)]. the safety and effectiveness of cresemba capsules for treatment of invasive aspergillosis have not been established in pediatric patients younger than 6 years of age or who weigh less than 16 kg because the oral route of administration was not assessed in this pediatric patient age cohort. the safety and effectiveness of cresemba for treatment of invasive aspergillosis in pediatric patients less than 1 year of age have not been established. invasive mucormycosis the safety and effectiveness of cresemba for injection for the treatment of invasive mucormycosis have been established in pediatric patients 1 year of age and older. the safety and effectiveness of cresemba capsules for the treatment of invasive mucormycosis have been established in pediatric patients 6 year of age and older weighing 16 kg and greater. use of cresemba in this age group for treatment of invasive mucormycosis is supported by one open-label trial in adult patients with invasive mucormycosis, a retrospective review of survival data for adult patients with untreated invasive mucormycosis, and additional pharmacokinetic and safety data in pediatric patients 1 year of age and older [see clinical pharmacology (12.3 )]. adverse reactions in this pediatric population were similar to those reported in the adult population [see adverse reaction s (6.1)]. the safety and effectiveness of cresemba capsules for treatment of invasive mucormycosis have not been established in pediatric patients younger than 6 years of age who weigh less than 16 kg because the oral route of administration was not assessed in this pediatric patient age cohort. the safety and effectiveness of cresemba for treatment of invasive mucormycosis in pediatric patients less than 1 year of age have not been established. of the 547 patients who received cresemba in the phase 2 and 3 trials, 86 (16%) of patients were greater than 65 years of age and 20 (4%) were greater than 75 years of age. the pharmacokinetics of isavuconazole are comparable in young and elderly subjects (65 years of age and older) [see clinical pharmacology (12.3)] . no dose adjustment of cresemba is needed in elderly patients. 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 elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. of the 403 patients who received cresemba in the phase 3 trials, 79 (20%) of patients had an estimated glomerular filtration rate (gfr) less than 60 ml/min/1.73 m2 . no dose adjustment is needed in patients with mild, moderate, or severe renal impairment, including those patients with end-stage renal disease (esrd) [see clinical pharmacology (12.3)] . no dose adjustment is necessary in patients with mild or moderate hepatic impairment (child-pugh class a and b) [see clinical pharmacology (12.3)] . cresemba has not been studied in patients with severe hepatic impairment (child-pugh class c) and should be used in these patients only when the benefits outweigh the risks. clinical monitoring for cresemba-related adverse reactions is recommended when treating patients with severe hepatic impairment [see warnings and precautions (5.1)] .

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

contract pharmacy services-pa - olanzapine (unii: n7u69t4szr) (olanzapine - unii:n7u69t4szr) - olanzapine 10 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 13-17), 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 dyslipidema. 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

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

contract pharmacy services-pa - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - bupropion hydrochloride 150 mg - bupropion hydrochloride extended-release tablets (sr) are indicated for the treatment of major depressive disorder (mdd), as defined by the diagnostic and statistical manual (dsm ) . the efficacy of bupropion in the treatment of a major depressive episode was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult subjects with mdd [see clinical studies ( 14) ] . the efficacy of bupropion hydrochloride extended-release tablets (sr) in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial [see clinical studies ( 14) ]. - bupropion hydrochloride extended-release tablets (sr) are contraindicated in patients with a seizure disorder. - bupropion hydrochloride extended-release tablets (sr) are contraindicated in patients with a current or prior diagnosis of bulimia or anorexi

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

zydus pharmaceuticals usa inc. - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 250 mg - divalproex sodium extended-release tablets are valproate and are indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. a manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. a mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode (depressed mood, loss of interest or pleasure in nearly all activities). the efficacy of divalproex sodium extended-release tablets  is based in part on studies of divalproex sodium delayed release tablets in this indication, and was confirmed in a 3 week trial with patients meeting dsm-iv tr criteria for bipolar i disorder, manic or mixed type, who were hospitalized for acute mania [see clinical studies (14.1)] . the effectiveness of valproate for long-term use in mania, i.e., more than 3 weeks, has not been demonstrated in controlled clinical trials. therefore, healthcare providers who elect to use divalproex sodium extended-release tablets for extended periods should continually reevaluate the long-term risk-benefits of the drug for the individual patient. divalproex sodium extended-release tablets 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 extended-release tablets are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures in adults and children 10 years of age or older, and adjunctively in adults and children 10 years of age or older 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. divalproex sodium extended-release tablets are indicated for prophylaxis of migraine headaches. there is no evidence that divalproex sodium extended-release tablets are useful in the acute treatment of migraine headaches. 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, divalproex sodium extended-release tablets are contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)] . -   divalproex sodium extended-release tablets should not be administered to patients with hepatic disease or significant hepatic dysfunction [see warnings and precautions (5.1)] . -   divalproex sodium extended-release tablets 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 extended-release tablets are contraindicated in patients with known hypersensitivity to the drug[see warnings and precautions (5.12)] . -   divalproex sodium extended-release tablets are contraindicated in patients with known urea cycle disorders[see warnings and precautions (5.6)] . -   for use in prophylaxis of migraine headaches: divalproex sodium extended-release tablets 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 extended-release tablets, during pregnancy. encourage women who are taking divalproex sodium extended-release tablets 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 (6.4)] . 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 extended-release tablets 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 (2.5)] . there is insufficient information available to discern the safety and effectiveness of valproate for the prophylaxis of migraines in patients over 65. 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) ] .

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

pd-rx pharmaceuticals, inc. - phentermine hydrochloride (unii: 0k2i505otv) (phentermine - unii:c045tql4wp) - phentermine hydrochloride 37.5 mg - phentermine hydrochloride, usp 37.5 mg is indicated as short-term (a few weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity for patients with an initial body mass index greater than or equal to 30 kg/m 2 , or greater than or equal to 27 kg/m 2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia). below is a chart of body mass index (bmi) based on various heights and weights. bmi is calculated by taking the patient’s weight, in kilograms (kg), divided by the patient’s height, in meters (m), squared. metric conversions are as follows: pounds ÷ 2.2 = kg; inches x 0.0254 = meters. the limited usefulness of agents of this class, including phentermine hydrochloride, [see clinical pharmacology ( 12.1, 12.2) ] should be measured against possible risk factors inherent in their use such as those described below. - history of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension) - during or within 14 days following the administration of monoamine oxidase inhibitors - hyperthyroidism - glaucoma - agitated states - history of drug abuse - pregnancy [see use in specific populations ( 8.1) ] - nursing [see use in specific populations ( 8.3) ] - known hypersensitivity, or idiosyncrasy to the sympathomimetic amines pregnancy category x phentermine is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. a minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to obligatory weight gain that occurs in maternal tissues during pregnancy. phentermine has pharmacologic activity similar to amphetamine (d- and d/l-amphetamine) [ see clinical pharmacology ( 12.1) ]. animal reproduction studies have not been conducted with phentermine. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. it is not known if phentermine is excreted in human milk; however, other amphetamines are present in human milk. because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. safety and effectiveness in pediatric patients have not been established. because pediatric obesity is a chronic condition requiring long-term treatment, the use of this product, approved for short-term therapy, is not recommended. in general, dose selection for an elderly patient should be cautious, 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. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. based on the reported excretion of phentermine in urine, exposure increases can be expected in patients with renal impairment [ see clinical pharmacology ( 12.3) ]. use caution when administering phentermine hydrochloride to patients with renal impairment. in patients with severe renal impairment (egfr 15 to 29 ml/min/1.73 m 2 ), limit the dosage of phentermine hydrochloride to 15 mg daily [see dosage and administration ( 2.2)]. phentermine hydrochloride has not been studied in patients with egfr less than 15 ml/min/1.73 m 2 , including end-stage renal disease requiring dialysis; avoid use in these populations. phentermine is a schedule iv controlled substance. phentermine is related chemically and pharmacologically to the amphetamines. amphetamines and other stimulant drugs have been extensively abused and the possibility of abuse of phentermine should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program. abuse of amphetamines and related drugs may be associated with intense psychological dependence and severe social dysfunction. there are reports of patients who have increased the dosage of these drugs to many times that recommended. abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep eeg. manifestations of chronic intoxication with anorectic drugs include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes. a severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.

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

coupler enterprises - cyclobenzaprine hydrochloride (unii: 0ve05jys2p) (cyclobenzaprine - unii:69o5wqq5ti) - cyclobenzaprine hydrochloride 10 mg - cyclobenzaprine hcl tablets usp are indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. improvement is manifested by relief of muscle spasm and its associated signs and symptoms, namely, pain, tenderness, limitation of motion, and restriction in activities of daily living. cyclobenzaprine hcl should be used only for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration and specific therapy for longer periods is seldom warranted.   cyclobenzaprine hcl has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy. hypersensitivity to any component of this product. concomitant use of monoamine oxidase (mao) inhibitors or within 14 days after their disco

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

contract pharmacy services-pa - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - bupropion hydrochloride 150 mg - bupropion hydrochloride extended-release tablets (xl) are indicated for the treatment of major depressive disorder (mdd), as defined by the diagnostic and statistical manual (dsm). the efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with mdd. the efficacy of the sustained-release formulation of bupropion in the maintenance treatment of mdd was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8-week study of acute treatment [see clinical studies ( 14.1) ]. bupropion hydrochloride extended-release tablets (xl) are indicated for the prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (sad). the efficacy of bupropion hydrochloride extended-release tablets in the prevention of seasonal major depressive episodes was