Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - quinine sulfate (unii: kf7z0e0q2b) (quinine - unii:a7v27phc7a) - quinine sulfate 324 mg - qualaquin is an antimalarial drug indicated only for treatment of uncomplicated plasmodium falciparum malaria. quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented [see clinical studies (14) ]. limitations of use: qualaquin is not approved for: qualaquin is contraindicated in patients with the following: risk summary prolonged experience with quinine in pregnant women over several decades, based on published prospective and retrospective observational studies, surveys, safety and efficacy studies, review articles, case reports and case series have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see data) . in animal reproduction studies, administration of quinine by multiple routes of administration to pregnant rabbits, dogs, guinea pigs, rats, and monkeys during the period of organogenesis at doses of 0.25 to 2 times the maximum recommended human dose (mrhd) based on body su

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - quinine sulfate (unii: kf7z0e0q2b) (quinine - unii:a7v27phc7a) - quinine sulfate 324 mg - quinine sulfate capsules are an antimalarial drug indicated only for treatment of uncomplicated plasmodium falciparum malaria. quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented [see clinical studies (14) ]. limitations of use: quinine sulfate oral capsules are not approved for: quinine sulfate capsules are contraindicated in patients with the following: risk summary prolonged experience with quinine in pregnant women over several decades, based on published prospective and retrospective observational studies, surveys, safety and efficacy studies, review articles, case reports and case series have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see data) . in animal reproduction studies, administration of quinine by multiple routes of administration to pregnant rabbits, dogs, guinea pigs, rats, and monkeys during the period of organogenesis at doses of 0.25 to 2 times the m

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - zolpidem tartrate (unii: wy6w63843k) (zolpidem - unii:7k383oqi23) - zolpidem tartrate 6.25 mg - zolpidem tartrate extended-release tablets, usp are indicated for the short-term treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset). the clinical trials performed in support of efficacy were up to 3 weeks (using polysomnography measurement up to 2 weeks in both adult and elderly patients) and 24 weeks (using patient-reported assessment in adult patients only) in duration [see clinical studies (14)] .  zolpidem tartrate extended-release tablets are contraindicated in patients - who have experienced complex sleep behaviors after taking zolpidem tartrate extended-release 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

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 125 mg - divalproex sodium is a valproate and is indicated for the treatment of the manic episodes associated with bipolar disorder. 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. the efficacy of divalproex sodium delayed-release tablets was established in 3-week trials with patients meeting dsm-iii-r criteria for bipolar disorder who were hospitalized for acute mania [see clinical studies (14.1)] . the safety and effectiveness of divalproex sodium delayed-release tablets  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 delayed-release tablets  for extended periods should continually reevaluate the long-term usefulness of the drug for the  individual patient. divalproex sodium delayed-release tablets are indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. divalproex sodium delayed-release tablets  are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures. simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. complex absence is the term used when other signs are also present. divalproex sodium delayed-release tablets are indicated for prophylaxis of migraine headaches. there is no evidence that divalproex sodium delayed-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 is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)]. - divalproex sodium should not be administered to patients with hepatic disease or significant hepatic dysfunction [see warnings and precautions (5.1)]. - divalproex sodium is 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 is contraindicated in patients with known hypersensitivity to the drug [see warnings and precautions (5.12)]. - divalproex sodium is contraindicated in patients with known urea cycle disorders [see warnings and precautions (5.6)]. - for use in prophylaxis of migraine headaches: divalproex sodium is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see warnings and precautions (5.2, 5.3, 5.4) and use in specific populations (8.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), including divalproex sodium delayed-release tablets, during pregnancy. encourage women who are taking divalproex sodium delayed-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 delayed-release tablets 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 delayed-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 delayed-release tablets were 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 sprinkle 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 delayed-release tablets 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 (2.4)] . there is insufficient information available to discern the safety and effectiveness of valproate for the prophylaxis of migraines in patients over 65.

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - desvenlafaxine (unii: ng99554anw) (desvenlafaxine - unii:ng99554anw) - desvenlafaxine 50 mg - desvenlafaxine is indicated for the treatment of adults with major depressive disorder (mdd) [see clinical studies (14)] . - hypersensitivity to desvenlafaxine succinate, venlafaxine hydrochloride or to any excipients in the desvenlafaxine extended-release tablets formulation.  angioedema has been reported in patients treated with desvenlafaxine [see adverse reactions (6.1)] . - the use of maois intended to treat psychiatric disorders with desvenlafaxine or within 7 days of stopping treatment with desvenlafaxine is contraindicated because of an increased risk of serotonin syndrome. the use of desvenlafaxine 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 desvenlafaxine 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 (2.8) and

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - dexmethylphenidate hydrochloride (unii: 1678ok0e08) (dexmethylphenidate - unii:m32rh9mfgp) - dexmethylphenidate hydrochloride 2.5 mg - dexmethylphenidate hydrochloride tablets are indicated for the treatment of attention deficit hyperactivity disorder (adhd) [see clinical studies ( 14)] . - hypersensitivity to methylphenidate or other components of dexmethylphenidate hydrochloride tablets. hypersensitivity reactions, such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [see adverse reactions ( 6.1)] . - concomitant treatment with monoamine oxidase inhibitors (maois), or within 14 days following discontinuation of treatment with an maoi, because of the risk of hypertensive crises [see drug interactions ( 7.1)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications, including dexmethylphenidate hydrochloride tablets, during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for adhd medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/. risk summary dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there may be risks to the fetus associated with the use of cns stimulants during pregnancy (see clinical considerations). embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to 5 times the maximum recommended human dose (mrhd) of 20 mg/day given to adults based on plasma levels. a decrease in pup weight in males was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 5 times the mrhd of 20 mg/day given to adults based on plasma levels. plasma levels in adults were comparatively similar to plasma levels in adolescents (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 fetal/neonatal adverse reactions cns stimulants, such as dexmethylphenidate hydrochloride tablets, can cause vasoconstriction and thereby decrease placental perfusion. no fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers. data animal data in embryo-fetal development studies conducted in rats and rabbits, dexmethylphenidate was administered orally at doses of up to 20 and 100 mg/kg/day, respectively, during the period of organogenesis. no evidence of malformations was found in either the rat or rabbit study; however, delayed fetal skeletal ossification was observed at the highest dose level in rats. when dexmethylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 20 mg/kg/day, post-weaning body weight gain was decreased in male offspring at the highest dose, but no other effects on postnatal development were observed. at the highest doses tested, plasma levels [area under the curves (aucs)] of dexmethylphenidate in pregnant rats and rabbits were approximately 5 and 1 times, respectively, those in adults dosed with the mrhd of 20 mg/day. racemic methylphenidate has been shown to cause malformations (increased incidence of fetal spina bifida) in rabbits when given in doses of 200 mg/kg/day throughout organogenesis. risk summary dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. limited published literature, based on milk sampling from seven mothers’ reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. there are no reports of adverse effects on the breastfed infant and no effects on milk production. long-term neurodevelopmental effects on infants from stimulant exposure are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dexmethylphenidate hydrochloride tablets, and any potential adverse effects on the breastfed infant from dexmethylphenidate hydrochloride tablets or from the underlying maternal condition. clinical considerations monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain. the safety and effectiveness of dexmethylphenidate hydrochloride tablets have been established in pediatric patients aged 6 to 17 years in two adequate and well-controlled clinical trials [see clinical studies ( 14)] . the safety and effectiveness of dexmethylphenidate hydrochloride tablets in pediatric patients aged less than 6 years have not been established. the long-term efficacy of dexmethylphenidate hydrochloride tablets in pediatric patients has not been established. long term suppression of growth growth should be monitored during treatment with stimulants, including dexmethylphenidate hydrochloride tablets. pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see warnings and precautions ( 5.7)] juvenile animal toxicity data rats treated with racemic methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. a deficit in acquisition of a specific learning task was observed in females only. the doses at which these findings were observed are at least 6 times the mrhd of 60 mg/day given to children on a mg/m 2 basis. in a study conducted in young rats, racemic methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal day 7) and continuing through sexual maturity (postnatal week 10). when these animals were tested as adults (postnatal weeks 13 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the mrhd of 60 mg of racemic methylphenidate given to children on a mg/m 2 basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (8 times the mrhd given to children on a mg/m 2 basis). the no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (approximately 0.5 times the mrhd given to children on a mg/m 2 basis). the clinical significance of the long-term behavioral effects observed in rats is unknown. dexmethylphenidate hydrochloride tablets have not been studied in the geriatric population. dexmethylphenidate hydrochloride tablets contain dexmethylphenidate hydrochloride, a schedule ii controlled substance. dexmethylphenidate hydrochloride tablets has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see warnings and precautions (5.1)] . dexmethylphenidate hydrochloride tablets can be diverted for non-medical use into illicit channels or distribution. abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of methylphenidate may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with cns stimulants abuse and/or misuse. misuse and abuse of cns stimulants, including dexmethylphenidate hydrochloride tablets, can result in overdose and death [see overdosage (10)], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. physical dependence dexmethylphenidate hydrochloride tablets may produce physical dependence. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of cns stimulants including dexmethylphenidate hydrochloride tablets include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation. tolerance dexmethylphenidate hydrochloride tablets may produce tolerance. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - methylphenidate hydrochloride (unii: 4b3sc438hi) (methylphenidate - unii:207zz9qz49) - methylphenidate hydrochloride 5 mg - methylphenidate hydrochloride tablets are indicated for the treatment of: - attention deficit hyperactivity disorders (adhd) in pediatric patients 6 years and older and adults - narcolepsy - hypersensitivity to methylphenidate or other components of methylphenidate hydrochloride tablets. hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been reported in patients treated with methylphenidate [ see adverse reactions (6.1)]. - concomitant treatment with monoamine oxidase inhibitors (maois), or within 14 days following discontinuation of treatment with an maoi, because of the risk of hypertensive crises [ see drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications, including methylphenidate hydrochloride tablets, during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for adhd medications at 1-866-961-2388 or visit https://womensmentalhealth.org/adhd-medications/. risk summary published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there may be risks to the fetus associated with the use of cns stimulants use during pregnancy (see clinical considerations). no effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses up to 10 and 15 times, respectively, the maximum recommended human dose (mrhd) of 60 mg/day given to adolescents on a mg/m 2 basis. however, spina bifida was observed in rabbits at a dose 52 times the mrhd given to adolescents. a decrease in pup body weight was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 6 times the mrhd given to adolescents (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 fetal/neonatal adverse reactions cns stimulants, such as methylphenidate hydrochloride tablets, can cause vasoconstriction and thereby decrease placental perfusion. no fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers. data animal data in embryo-fetal development studies conducted in rats and rabbits, methylphenidate was administered orally at doses of up to 75 and 200 mg/kg/day, respectively, during the period of organogenesis. malformations (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 52 times the mrhd of 60 mg/day given to adolescents on a mg/m 2 basis. the no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (15times the mrhd given to adolescents on a mg/m 2 basis). there was no evidence of morphological development effects in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (10 times the mrhd of 60 mg/day given to adolescents on a mg/m 2 basis), which was also maternally toxic. the no effect level for embryo-fetal development in rats was 25 mg/kg/day (3 times the mrhd on a mg/m 2 basis). when methylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 45 mg/kg/day, offspring body weight gain was decreased at the highest dose (6 times the mrhd of 60 mg/day given to adolescents on a mg/m 2 basis), but no other effects on postnatal development were observed. the no effect level for pre- and postnatal development in rats was 15 mg/kg/day (approximately 2 times the mrhd given to adolescents on a mg/m 2 basis). risk summary limited published literature, based on milk sampling from seven mothers reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. there are no reports of adverse effects on the breastfed infant and no effects on milk production. long-term neurodevelopmental effects on infants from stimulant exposure are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for methylphenidate hydrochloride tablets and any potential adverse effects on the breastfed infant from methylphenidate hydrochloride tablets or from the underlying maternal condition. clinical considerations monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain. the safety and effectiveness of methylphenidate hydrochloride tablets for the treatment of adhd have been established in pediatric patients aged 6 to 17 years. the safety and effectiveness of methylphenidate hydrochloride tablets in pediatric patients aged less than 6 years have not been established. the long-term efficacy of methylphenidate in pediatric patients has not been established. long-term suppression of growth growth should be monitored during treatment with stimulants, including methylphenidate hydrochloride tablets. pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [ see warnings and precautions (5.7)] . juvenile animal toxicity data rats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. a deficit in acquisition of a specific learning task was observed in females only. the doses at which these findings were observed are at least 4 times the mrhd of 60 mg/day given to children on a mg/m 2 basis. in a study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal day 7) and continuing through sexual maturity (postnatal week 10). when these animals were tested as adults (postnatal weeks 13 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the mrhd of 60 mg/day given to children on a mg/m 2 basis) or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (8 times the mrhd given to children on a mg/m 2 basis). the no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (approximately 0.5 timesthe mrhd given to children on a mg/m 2 basis). the clinical significance of the long-term behavioral effects observed in rats is unknown. methylphenidate hydrochloride tablets have not been studied in the geriatric population. methylphenidate hydrochloride tablets contain methylphenidate hydrochloride, a schedule ii controlled substance. methylphenidate hydrochloride tablets has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see warnings and precautions (5.1)]. methylphenidate hydrochloride tablets can be diverted for non-medical use into illicit channels or distribution. abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of methylphenidate hydrochloride may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with cns stimulants abuse and/or misuse. misuse and abuse of cns stimulants, including methylphenidate hydrochloride tablets, can result in overdose and death [see overdosage (10)], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. physical dependence methylphenidate hydrochloride tablets may produce physical dependence. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of cns stimulants including methylphenidate hydrochloride tablets include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation. tolerance methylphenidate hydrochloride tablets may produce tolerance. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - levetiracetam (unii: 44yrr34555) (levetiracetam - unii:44yrr34555) - levetiracetam 500 mg - levetiracetam extended-release tablets are indicated for the treatment of partial-onset seizures in patients 12 years of age and older. levetiracetam extended-release tablets are contraindicated in patients with a hypersensitivity to levetiracetam. reactions have included anaphylaxis and angioedema [see warnings and precautions (5.4)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), including levetiracetam extended-release tablets, during pregnancy. encourage women who are taking levetiracetam extended-release tablets during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary prolonged experience with levetiracetam in pregnant women has not identified a drug-associated risk of major birth defects or miscarriage, based on published literature, which includes data from pregnancy regis

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - oxycodone hydrochloride (unii: c1enj2te6c) (oxycodone - unii:cd35pmg570) - oxycodone hydrochloride 5 mg - oxycodone hydrochloride tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)], reserve oxycodone hydrochloride tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): oxycodone hydrochloride tablets are contraindicated in patients with: prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] . available data with oxycodone hydrochloride tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. animal reproduction studies with oral administrations of oxycodone hcl in rats and rabbits during the period of organogenesis at doses 2.6 and 8.1 times, respectively, the

Estados Unidos - inglês - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - zonisamide (unii: 459384h98v) (zonisamide - unii:459384h98v) - zonisamide 25 mg - zonisamide is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy. zonisamide is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide. the abuse and dependence potential of zonisamide has not been evaluated in human studies (see warnings, cognitive/neuropsychiatric adverse events subsection). in a series of animal studies, zonisamide did not demonstrate abuse liability and dependence potential. monkeys did not self-administer zonisamide in a standard reinforcing paradigm. rats exposed to zonisamide did not exhibit signs of physical dependence of the cns-depressant type. rats did not generalize the effects of diazepam to zonisamide in a standard discrimination paradigm after training, suggesting that zonisamide does not have abuse potential of the benzodiazepine-cns depressant type.