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sun pharmaceutical industries, inc. - citalopram hydrobromide (unii: i1e9d14f36) (citalopram - unii:0dhu5b8d6v) - citalopram 10 mg - citalopram tablets, usp (citalopram hbr) is indicated for the treatment of depression. the efficacy of citalopram tablets, usp in the treatment of depression was established in 4-6 week, controlled trials of outpatients whose diagnosis corresponded most closely to the dsm-iii and dsm-iii-r category of major depressive disorder (see clinical pharmacology ). 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. the antidepressant action of citalopram tablets, usp in hospitalized depressed patients has no

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sun pharmaceutical industries, inc. - topiramate (unii: 0h73wjj391) (topiramate - unii:0h73wjj391) - topiramate 25 mg - topiramate tablets, usp are indicated as initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures. safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials [see clinical studies (14.1)] . topiramate tablets, usp are indicated as adjunctive therapy for adults and pediatric patients ages 2 to 16 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome [see clinical studies (14.2)] . none. pregnancy category d. [see warnings and precautions (5.7)] topiramate can cause fetal harm when administered to a pregnant woman. data from pregnancy registries indicate that infants exposed to topiramate in utero have an increased risk for cleft lip and/or cleft palate (oral clefts). when multiple species of pregnant animals received

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sun pharmaceutical industries, inc. - dexmethylphenidate hydrochloride (unii: 1678ok0e08) (dexmethylphenidate - unii:m32rh9mfgp) - dexmethylphenidate hydrochloride extended-release capsules are indicated for the treatment of attention deficit hyperactivity disorder (adhd) [ see clinical studies ( 14) ]. - hypersensitivity to methylphenidate or other components of dexmethylphenidate hydrochloride extended-release capsules. 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 extended-release capsules, 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 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 (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 extended-release capsules, 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 20 mg/day. plasma levels in adults were comparatively similar to plasma levels in adolescents. 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 extended-release capsule and any potential adverse effects on the breastfed infant from dexmethylphenidate hydrochloride extended-release capsule 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 extended-release capsules for the treatment of adhd have been established in pediatric patients aged 6 to 17 years in two adequate and well-controlled clinical trials [see clinical studies ( 14.2)] . the safety and effectiveness of dexmethylphenidate hydrochloride extended-release capsules in pediatric patients aged less than 6 years have not been established. the long-term efficacy of dexmethylphenidate hydrochloride extended-release capsules in pediatric patients has not been established. long term suppression of growth growth should be monitored during treatment with stimulants, including dexmethylphenidate hydrochloride extended-release capsules. 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/day 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 extended-release capsules have not been studied in the geriatric population. dexmethylphenidate hydrochloride extended-release capsules contain dexmethylphenidate hydrochloride, a schedule ii controlled substance. dexmethylphenidate hydrochloride extended-release capsules have 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 extended-release capsules 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 extended-release capsules, 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 extended-release capsules 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 extended-release capsules include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation. tolerance dexmethylphenidate hydrochloride extended-release capsules 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).

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sun pharmaceutical industries, inc. - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd) in adults. trazodone hydrochloride tablets are contraindicated in: - patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions (5.2), drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/ pregnancyregistry/antidepressants/ risk summary published prospective cohort studies, case series, and case reports over several decades with desyrel use in preg

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sun pharmaceutical industries, inc. - lisdexamfetamine dimesylate (unii: sjt761gegs) (lisdexamfetamine - unii:h645gul8kj) - lisdexamfetamine dimesylate capsules and lisdexamfetamine dimesylate chewable tablets are indicated for the treatment of: - attention deficit hyperactivity disorder (adhd) in adults and pediatric patients 6 years and older [see clinical studies ( 14.1)] - moderate to severe binge eating disorder (bed) in adults [see clinical studies ( 14.2)] . limitations of use: - pediatric patients with adhd younger than 6 years of age experienced more long-term weight loss than patients 6 years and older [see use in specific populations ( 8.4)]. - lisdexamfetamine dimesylate is not indicated or recommended for weight loss. use of other sympathomimetic drugs for weight loss has been associated with serious cardiovascular adverse events. the safety and effectiveness of lisdexamfetamine dimesylate for the treatment of obesity have not been established [see warnings and precautions ( 5.2)] . lisdexamfetamine dimesylate is contraindicated in patients with: - known hypersensitivity to amphetamine products or other ingredients of lisdexamfetamine dimesylate capsules and lisdexamfetamine dimesylate chewable tablets. anaphylactic reactions, stevens-johnson syndrome, angioedema, and urticaria have been observed in postmarketing reports [see adverse reactions ( 6.2)] . - patients taking monoamine oxidase inhibitors (maois), or within 14 days of stopping maois (including maois such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see warnings and precautions ( 5.7) and drug interactions ( 7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to adhd medications during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and researchprograms/pregnancyregistry/adhd-medications/. risk summary the limited available data from published literature and postmarketing reports on use of lisdexamfetamine dimesylate in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines [see clinical considerations] . in animal reproduction studies, lisdexamfetamine dimesylate (a prodrug of d-amphetamine) had no effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis. pre- and postnatal studies were not conducted with lisdexamfetamine dimesylate. however, amphetamine (d- to l- ratio of 3:1) administration to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine. in addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine. long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine [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 2-4% and 15-20%, respectively. clinical considerations fetal/neonatal adverse reactions amphetamines, such as lisdexamfetamine dimesylate, cause vasoconstriction and thereby may decrease placental perfusion. in addition, amphetamines can stimulate uterine contractions increasing the risk of premature delivery. infants born to amphetamine-dependent mothers have an increased risk of premature delivery and low birth weight. monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness. data animal data lisdexamfetamine dimesylate had no apparent effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 40 and 120 mg/kg/day, respectively. these doses are approximately 5.5 and 33 times, respectively, the maximum recommended human dose (mrhd) of 70 mg/day given to adults, on a mg/m 2 body surface area basis. a study was conducted with amphetamine (d- to l- enantiomer ratio of 3:1) in which pregnant rats received daily oral doses of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. all doses caused hyperactivity and decreased weight gain in the dams. a decrease in pup survival was seen at all doses. a decrease in pup body weight was seen at 6 and 10 mg/kg which correlated with delays in developmental landmarks, such as preputial separation and vaginal opening. increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. when pups were tested for reproductive performance at maturation, gestational weight gain, number of implantations, and number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg. a number of studies from the literature in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d, l-) at doses similar to those used clinically can result in long-term neurochemical and behavioral alterations. reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function. risk summary lisdexamfetamine is a pro-drug of dextroamphetamine. based on limited case reports in published literature, amphetamine (d-or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. there are no reports of adverse effects on the breastfed infant. long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. it is possible that large dosages of dextroamphetamine might interfere with milk production, especially in women whose lactation is not well established. because of the potential for serious adverse reactions in nursing infants, including serious cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy, advise patients that breastfeeding is not recommended during treatment with lisdexamfetamine dimesylate. adhd safety and effectiveness of lisdexamfetamine dimesylate have been established in pediatric patients with adhd ages 6 to 17 years [see dosage and administration ( 2.3), adverse reactions ( 6.1), clinical pharmacology ( 12.3), and clinical studies ( 14.1)] . safety and effectiveness of lisdexamfetamine dimesylate have not been established in pediatric patients below the age of 6 years. safety and efficacy of lisdexamfetamine dimesylate were evaluated in a double-blind, randomized, parallel-group, placebo-controlled, fixed-dose study in pediatric patients ages 4 to 5 years with adhd, followed by a 1-year open-label extension study. in these studies, patients experienced elevated rates of adverse reactions, including weight loss, decreased bmi, decreased appetite, insomnia, infections (upper respiratory and nasopharyngitis), irritability, and affect lability. with the same lisdexamfetamine dimesylate dose, mean steady state exposure of dextroamphetamine was approximately 44% higher in pediatric patients ages 4 to 5 years compared to the pediatric patients ages 6 to 11 years. bed safety and effectiveness of lisdexamfetamine dimesylate have not been established in pediatric patients with bed less than 18 years of age. growth suppression growth should be monitored during treatment with stimulants, including lisdexamfetamine dimesylate, and pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see warnings and precautions ( 5.5) and adverse reactions ( 6.1)] . juvenile animal data studies conducted in juvenile rats and dogs at clinically relevant doses showed growth suppression that partially or fully reversed in dogs and female rats but not in male rats after a four-week drug-free recovery period. a study was conducted in which juvenile rats received oral doses of 4, 10, or 40 mg/kg/day of lisdexamfetamine dimesylate from day 7 to day 63 of age. these doses are approximately 0.3, 0.7, and 3 times the maximum recommended human daily dose of 70 mg on a mg/m 2 basis for a child. dose-related decreases in food consumption, bodyweight gain, and crown-rump length were seen; after a four-week drug-free recovery period, bodyweights and crown-rump lengths had significantly recovered in females but were still substantially reduced in males. time to vaginal opening was delayed in females at the highest dose, but there were no drug effects on fertility when the animals were mated beginning on day 85 of age. in a study in which juvenile dogs received lisdexamfetamine dimesylate for 6 months beginning at 10 weeks of age, decreased bodyweight gain was seen at all doses tested (2, 5, and 12 mg/kg/day, which are approximately 0.5, 1, and 3 times the maximum recommended human daily dose on a mg/m 2 basis for a child). this effect partially or fully reversed during a four- week drug-free recovery period. clinical studies of lisdexamfetamine dimesylate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience and pharmacokinetic data [see clinical pharmacology ( 12.3)] have not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should start 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. due to reduced clearance in patients with severe renal impairment (gfr 15 to < 30 ml/min/1.73 m 2 ), the maximum dose should not exceed 50 mg/day. the maximum recommended dose in esrd (gfr < 15 ml/min/1.73 m 2 ) patients is 30 mg/day [see clinical pharmacology ( 12.3)] . lisdexamfetamine and d-amphetamine are not dialyzable. lisdexamfetamine dimesylate capsules and lisdexamfetamine dimesylate chewable tablets contain lisdexamfetamine, a prodrug of amphetamine, a schedule ii controlled substance. lisdexamfetamine dimesylate 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)]. lisdexamfetamine dimesylate 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 lisdexamfetamine, a prodrug of amphetamine, 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 lisdexamfetamine dimesylate, 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. studies of lisdexamfetamine dimesylate in drug abusers a randomized, double-blind, placebo-control, cross-over, abuse liability study in 38 patients with a history of drug abuse was conducted with single-doses of 50, 100, or 150 mg of lisdexamfetamine dimesylate, 40 mg of immediate-release d-amphetamine sulphate (a controlled ii substance), and 200 mg of diethylpropion hydrochloride (a controlled iv substance). lisdexamfetamine dimesylate 100 mg produced significantly less “drug liking effects” as measured by the drug rating questionnaire-subject score, compared to d-amphetamine 40 mg; and 150 mg of lisdexamfetamine dimesylate demonstrated similar “drug-liking effects” compared to 40 mg of d-amphetamine and 200 mg of diethylpropion. intravenous administration of 50 mg lisdexamfetamine dimesylate to individuals with a history of drug abuse produced positive subjective responses on scales measuring "drug liking", "euphoria", "amphetamine effects", and "benzedrine effects" that were greater than placebo but less than those produced by an equivalent dose (20 mg) of intravenous d-amphetamine. physical dependence lisdexamfetamine dimesylate 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 lisdexamfetamine dimesylate include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation. tolerance lisdexamfetamine dimesylate 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).

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sun pharmaceutical industries, inc. - acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d), hydrocodone bitartrate (unii: no70w886kk) (hydrocodone - unii:6yks4y3wq7) - acetaminophen 325 mg - hydrocodone bitartrate and acetaminophen tablets, usp are indicated for the management of moderate to moderately severe 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 ], reserve hydrocodone bitartrate and acetaminophen tablets, usp for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): hydrocodone bitartrate and acetaminophen tablets, usp are contraindicated in patients with:

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sun pharmaceutical industries, inc. - gabapentin (unii: 6cw7f3g59x) (gabapentin - unii:6cw7f3g59x) - gabapentin 100 mg - gabapentin is  indicated for: - management of postherpetic neuralgia in adults - adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.  pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), such as gabapentin, during pregnancy. encourage women who are taking gabapentin during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are no adequate data on the developmental risks associated with the use of gabapentin in pregnant women. in nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal

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sun pharmaceutical industries, inc. - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c) - morphine sulfate 15 mg - morphine sulfate extended-release tablets are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)] , reserve morphine sulfate extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - morphine sulfate extended-release tablets are not indicated as an as-needed (prn) analgesic. morphine sulfate is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.3)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.6)] - concurrent use of monoamine oxidase inhibitors (maois) or use of maois within the last 14 days [see warnings and precautions (5.7), drug interactions (7)] . - hypersensitivity (e.g., anaphylaxis) to morphine [see adverse reactions (6.2)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.11)] risk summary prolonged use of opioid analgesics during pregnancy may cause neonatal withdrawal syndrome [see warnings and precautions (5.4)]. there are no available data with morphine sulfate in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects [see human data]. in published animal reproduction studies, morphine administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 5 and 16 times the human daily dose of 60 mg based on body surface area (hdd) in hamsters and mice, respectively, lower fetal body weight and increased incidence of abortion at 0.4 times the hdd in the rabbit, growth retardation at 6 times the hdd in the rat, and axial skeletal fusion and cryptorchidism at 16 times the hdd in the mouse. administration of morphine sulfate to pregnant rats during organogenesis and through lactation resulted in cyanosis, hypothermia, decreased brain weights, pup mortality, decreased pup body weights, and adverse effects on reproductive tissues at 3 to 4 times the hdd; and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the hdd [see animal data ]. based on animal data, advise pregnant women of the potential risk to a fetus. 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 prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. morphine sulfate is not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including morphine sulfate, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. data human data the results from a population-based prospective cohort, including 70 women exposed to morphine during the first trimester of pregnancy and 448 women exposed to morphine at any time during pregnancy, indicate no increased risk for congenital malformations. however, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and non-randomized study design. animal data formal reproductive and developmental toxicology studies for morphine have not been conducted. exposure margins for the following published study reports are based on human daily dose of 60 mg morphine using a body surface area comparison (hdd). neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of morphine sulfate (35-322 mg/kg) on gestation day 8 to pregnant hamsters (4.7 to 43.5 times the hdd). a no adverse effect level was not defined in this study and the findings cannot be clearly attributed to maternal toxicity. neural tube defects (exencephaly), axial skeletal fusions, and cryptorchidism were reported following a single subcutaneous (sc) injection of morphine sulfate to pregnant mice (100-500 mg/kg) on gestation day 8 or 9 at 200 mg/kg or greater (16 times the hdd) and fetal resorption at 400 mg/kg or higher (32 times the hdd). no adverse effects were noted following 100 mg/kg morphine in this model (8 times the hdd). in one study, following continuous subcutaneous infusion of doses greater than or equal to 2.72 mg/kg to mice (0.2 times the hdd), exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted. the effects were reduced with increasing daily dose; possibly due to rapid induction of tolerance under these infusion conditions. the clinical significance of this report is not clear. decreased fetal weights were observed in pregnant rats treated with 20 mg/kg/day morphine sulfate (3.2 times the hdd) from gestation day 7 to 9. there was no evidence of malformations despite maternal toxicity (10% mortality). in a second rat study, decreased fetal weight and increased incidences of growth retardation were noted at 35 mg/kg/day (5.7 times the hdd) and there was a reduced number of fetuses at 70 mg/kg/day (11.4 times the hdd) when pregnant rats were treated with 10, 35, or 70 mg/kg/day morphine sulfate via continuous infusion from gestation day 5 to 20. there was no evidence of fetal malformations or maternal toxicity. an increased incidence of abortion was noted in a study in which pregnant rabbits were treated with 2.5 (0.8 times the hdd) to 10 mg/kg morphine sulfate via subcutaneous injection from gestation day 6 to 10. in a second study, decreased fetal body weights were reported following treatment of pregnant rabbits with increasing doses of morphine (10-50 mg/kg/day) during the pre-mating period and 50 mg/kg/day (16 times the hdd) throughout the gestation period. no overt malformations were reported in either publication; although only limited endpoints were evaluated. in published studies in rats, exposure to morphine during gestation and/or lactation periods is associated with: decreased pup viability at 12.5 mg/kg/day or greater (2 times the hdd); decreased pup body weights at 15 mg/kg/day or greater (2.4 times the hdd); decreased litter size, decreased absolute brain and cerebellar weights, cyanosis, and hypothermia at 20 mg/kg/day (3.2 times the hdd); alteration of behavioral responses (play, social-interaction) at 1 mg/kg/day or greater (0.2 times the hdd); alteration of maternal behaviors (e.g., decreased nursing and pup retrievals) in mice at 1 mg/kg or higher (0.08 times the hdd) and rats at 1.5 mg/kg/day or higher (0.2 times the hdd); and a host of behavioral abnormalities in the offspring of rats, including altered responsiveness to opioids at 4 mg/kg/day (0.7 times the hdd) or greater. fetal and/or postnatal exposure to morphine in mice and rats has been shown to result in morphological changes in fetal and neonatal brain and neuronal cell loss, alteration of a number of neurotransmitter and neuromodulator systems, including opioid and non-opioid systems, and impairment in various learning and memory tests that appear to persist into adulthood. these studies were conducted with morphine treatment usually in the range of 4 to 20 mg/kg/day (0.7 to 3.2 times the hdd). additionally, delayed sexual maturation and decreased sexual behaviors in female offspring at 20 mg/kg/day (3.2 times the hdd), and decreased plasma and testicular levels of luteinizing hormone and testosterone, decreased testes weights, seminiferous tubule shrinkage, germinal cell aplasia, and decreased spermatogenesis in male offspring were also observed at 20 mg/kg/day (3.2 times the hdd). decreased litter size and viability were observed in the offspring of male rats that were intraperitoneally administered morphine sulfate for 1 day prior to mating at 25 mg/kg/day (4.1 times the hdd) and mated to untreated females. decreased viability and body weight and/or movement deficits in both first and second generation offspring were reported when male mice were treated for 5 days with escalating doses of 120 to 240 mg/kg/day morphine sulfate (9.7 to 19.5 times the hdd) or when female mice treated with escalating doses of 60 to 240 mg/kg/day (4.9 to 19.5 times the hdd) followed by a 5-day treatment-free recovery period prior to mating. similar multigenerational findings were also seen in female rats pre-gestationally treated with escalating doses of 10 to 22 mg/kg/day morphine (1.6 to 3.6 times the hdd).  risk summary morphine is present in breast milk. published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine auc ratio of 2.5:1 measured in one lactation study. however, there is insufficient information to determine the effects of morphine on the breastfed infant and the effects of morphine on milk production. lactation studies have not been conducted with extended-release morphine, including morphine sulfate. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with morphine sulfate. clinical considerations monitor infants exposed to morphine sulfate through breast milk for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. infertility chronic use of opioids may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2)] . in published animal studies, morphine administration adversely effected fertility and reproductive endpoints in male rats and prolonged estrus cycle in female rats [see nonclinical toxicology (13)] . the safety and effectiveness in pediatric patients below the age of 18 have not been established. the pharmacokinetics of morphine sulfate have not been studied in elderly patients.  clinical studies of morphine sulfate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.  elderly patients (aged 65 years or older) may have increased sensitivity to morphine. in general, use caution when selecting a dosage for an elderly patient, 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. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of morphine sulfate slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see warnings and precautions (5.6)] . morphine is known to be substantially excreted by the kidney, and the risk of adverse 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. morphine pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. start these patients with a lower than usual dosage of morphine sulfate and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine pharmacokinetics are altered in patients with renal failure. start these patients with a lower than usual dosage of morphine sulfate and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see clinical pharmacology (12.3)]. morphine sulfate extended-release tablets contain morphine, a schedule ii controlled substance. morphine sulfate extended-release tablets contains morphine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and tapentadol. morphine sulfate can be abused and is subject to misuse, addiction, and criminal diversion [see warnings and precautions (5.1)] . the high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of morphine sulfate extended-release tablets abuse include those with a history of prolonged use of any opioid, including products containing morphine sulfate, those with a history of drug or alcohol abuse, or those who use morphine sulfate extended-release tablets in combination with other abused drugs. prescription drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal. “drug-seeking” behavior is very common in persons with substance use disorders. drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. abuse and addiction are separate and distinct from physical dependence and tolerance. healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. in addition, abuse of opioids can occur in the absence of true addiction. morphine sulfate, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of morphine sulfate morphine sulfate extended-release tablets are for oral use only. abuse of morphine sulfate poses a risk of overdose and death. this is increased with concurrent use of morphine sulfate with alcohol and/or other cns depressants.  taking cut, broken, chewed, crushed, or dissolved morphine sulfate extended-release tablets enhances drug release and increases the risk of overdose and death.  due to the presence of talc as one of the excipients in morphine sulfate, with parenteral abuse the inactive ingredients can result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury, embolism, and death. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during chronic opioid therapy. tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors).  tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects. physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug.  withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage. do not abruptly discontinue morphine sulfate in a patient physically dependent on opioids. rapid tapering of morphine sulfate in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing morphine sulfate, gradually taper the dosage using a patient-specific plan that considers the following: the dose of morphine sulfate the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.6), warnings and precautions (5.13)]. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1)] .

United States - English - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - potassium chloride (unii: 660yq98i10) (potassium cation - unii:295o53k152) - because of reports of intestinal and gastric ulceration and bleeding with controlled release potassium chloride preparations, these drugs should be reserved for those patients who cannot tolerate or refuse to take liquid or effervescent potassium preparations or for patients in whom there is a problem of compliance with these preparations. - for the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. if hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia. - for the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, e.g. digitalized patients or patients with significant cardiac arrhythmias. the use of potassium salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. serum potassium should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. in more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with potassium salts may be indicated. potassium supplements are contraindicated in patients with hyperkalemia since a further increase in serum potassium concentration in such patients can produce cardiac arrest. hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (e.g. spironolactone, triamterene, amiloride) (see overdosage ). controlled-release formulations of potassium chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. potassium supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of potassium chloride (see precautions: information for patients , and dosage and administration sections). all solid oral dosage forms of potassium chloride are contraindicated in any patient in whom there is structural, pathological (e.g. diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

United States - English - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - dextroamphetamine saccharate (unii: g83415v073) (dextroamphetamine - unii:tz47u051fi), amphetamine aspartate monohydrate (unii: o1zpv620o4) (amphetamine - unii:ck833kgx7e), dextroamphetamine sulfate (unii: jj768o327n) (dextroamphetamine - unii:tz47u051fi), amphetamine sulfate (unii: 6dpv8nk46s) (amphetamine - unii:ck833kgx7e) - dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules are indicated for the treatment of attention deficit hyperactivity disorder (adhd) in adults and pediatric patients 6 years and older. dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules administration is contraindicated in patients: - known to be hypersensitive to amphetamine, or other components of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules. hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other amphetamine products [see adverse reactions (6.2)] - taking monoamine oxidase inhibitors (maois), or within 14 days of stopping maois (including maois such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis [see warnings and precautions (5.6)and drug interactions (7.1)] pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/. risk summary available data from published epidemiologic studies and postmarketing reports on use of prescription amphetamine in pregnant women have not identified a drug-associated risk of major birth defects and miscarriage (see data). adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers taking amphetamines during pregnancy (see clinical considerations). no apparent effects on morphological development were observed in embryo-fetal development studies, with oral administration of amphetamine to rats and rabbits during organogenesis at doses 2 and 12 times, respectively, the maximum recommended human dose (mrhd) of 20 mg/day given to adolescents, on a mg/m 2 basis. however, in a pre- and post-natal development study, amphetamine (d- to l- ratio of 3:1) administered orally to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine. in addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine. long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine (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 2-4% and 15- 20%, respectively. clinical considerations fetal/neonatal adverse reactions amphetamines, such as dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules, cause vasoconstriction and thereby may decrease placental perfusion. in addition, amphetamines can stimulate uterine contractions, increasing the risk of premature delivery. infants born to mothers taking amphetamines during pregnancy have an increased risk of premature delivery and low birth weight. monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness. data animal data amphetamine (d- to l- enantiomer ratio of 3:1) had no apparent effects on embryofetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. these doses are approximately 2 and 12 times, respectively, the maximum recommended human dose (mrhd) of 20 mg/day given to adolescents, on a mg/m2 basis. fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 10 times the mrhd given to adolescents on a mg/m 2 basis) or greater to pregnant animals. administration of these doses was also associated with severe maternal toxicity. a study was conducted in which pregnant rats received daily oral doses of amphetamine (d- to l- enantiomer ratio of 3:1) of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. these doses are approximately 0.8, 2, and 4 times the mrhd of 20 mg/day given to adolescents, on a mg/m2 basis. all doses caused hyperactivity and decreased weight gain in the dams. a decrease in pup survival was seen at all doses. a decrease in pup body weight was seen at 6 and 10 mg/kg which correlated with delays in developmental landmarks, such as preputial separation and vaginal opening. increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. when pups were tested for reproductive performance at maturation, gestational weight gain, number of implantations, and number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg. a number of studies from the literature in rodents indicate that prenatal or early postnatal exposure to amphetamine (d- or d, l-) at doses similar to those used clinically can result in long-term neurochemical and behavioral alterations. reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function. risk summary based on limited case reports in published literature, amphetamine (d- or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. there are no reports of adverse effects on the breastfed infant. long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. it is possible that large dosages of amphetamine might interfere with milk production, especially in women whose lactation is not well established. because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules. the safety and effectiveness of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules have been established in pediatric patients with adhd 6 years of age and older. the safety and efficacy of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules in pediatric patients less than 6 years of age have not been established. long-term effects of amphetamines in pediatric patients has not been well established. long-term growth suppression growth should be monitored during treatment with stimulants, including dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules, and pediatric patients aged 6 to 17 years who are not growing or gaining weight as expected may need to have their treatment interrupted [see warnings and precautions (5.5)] . juvenile animal toxicity data juvenile rats treated with mixed amphetamine salts early in the postnatal period through sexual maturation demonstrated transient changes in motor activity. learning and memory was impaired at approximately 6 times the maximum recommended human dose (mrhd) given to children on a mg/m 2 basis. no recovery was seen following a drug-free period. a delay in sexual maturation was observed at a dose approximately 6 times the mrhd given to children on a mg/m 2 basis, although there was no effect on fertility. in a juvenile developmental study, rats received daily oral doses of amphetamine ( d to l enantiomer ratio of 3:1) of 2, 6, or 20 mg/kg on days 7 to 13 of age; from day 14 to approximately day 60 of age these doses were given b.i.d. for total daily doses of 4, 12, or 40 mg/kg. the latter doses are approximately 0.6, 2, and 6 times the mrhd of 30 mg/day, given to children on a mg/m 2 basis. post dosing hyperactivity was seen at all doses; motor activity measured prior to the daily dose was decreased during the dosing period but the decreased motor activity was largely absent after an 18 day drug-free recovery period. performance in the morris water maze test for learning and memory was impaired at the 40 mg/kg dose, and sporadically at the lower doses, when measured prior to the daily dose during the treatment period; no recovery was seen after a 19 day drug-free period. a delay in the developmental milestones of vaginal opening and preputial separation was seen at 40 mg/kg but there was no effect on fertility. dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules have not been studied in the geriatric population. due to reduced clearance of amphetamines in patients with severe renal impairment (gfr 15 to <30 ml/min/1.73m 2 ), the recommended dose should be reduced. dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules are not recommended in patients with esrd (gfr < 15 ml/min/1.73m 2 ) [see dosage and administration (2.5), clinical pharmacology (12.3)]. d-amphetamine is not dialyzable. dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules contain amphetamine, a schedule ii controlled substance. dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules 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)] . dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules 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 healthcare 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 amphetamine 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 dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules, 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 dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules 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 dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation. tolerance dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, amphetamine sulfate extended-release capsules 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).