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avpak - modafinil (unii: r3uk8x3u3d) (modafinil - unii:r3uk8x3u3d) - modafinil 100 mg - modafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (osa), or shift work disorder (swd). limitations of use in osa, modafinil tablets are indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. if continuous positive airway pressure (cpap) is the treatment of choice for a patient, a maximal effort to treat with cpap for an adequate period of time should be made prior to initiating and during treatment with modafinil tablets for excessive sleepiness. modafinil tablets are contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients [see warnings and precautions (5.1, 5.2, 5.3)] . teratogenic effects pregnancy category c there are no adequate and well-controlled studies of modafinil in pregnant

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avpak - pantoprazole sodium (unii: 6871619q5x) (pantoprazole - unii:d8tst4o562) - pantoprazole 20 mg - pantoprazole sodium delayed-release tablets, usp are indicated for: pantoprazole is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis (ee). for those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole may be considered. safety of treatment beyond 8 weeks in pediatric patients has not been established. pantoprazole is indicated for maintenance of healing of ee and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gerd. controlled studies did not extend beyond 12 months. pantoprazole is indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison (ze) syndrome. - pantoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. hypersensitivity reactions may includ

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avpak - olanzapine (unii: n7u69t4szr) (olanzapine - unii:n7u69t4szr) - olanzapine 5 mg -            oral olanzapine is indicated for the treatment of schizophrenia. efficacy was established in three clinical trials in adult patients with schizophrenia: two 6-week trials and one maintenance trial. in adolescent patients with schizophrenia (ages 13 to 17), efficacy was established in one 6-week trial [see clinical studies (14.1)] .            when deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see warnings and precautions (5.5)] .             monotherapy — oral olanzapine is indicated for the acute treatment of manic or mixed episodes associated with bipolar i disorder and maintenance treatment of bipolar i disorder. efficacy w

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avpak - moxifloxacin hydrochloride (unii: c53598599t) (moxifloxacin - unii:u188xyd42p) - moxifloxacin 400 mg - to reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin hydrochloride tablets and other antibacterial drugs, moxifloxacin hydrochloride tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. moxifloxacin hydrochloride tablets are indicated for the treatment of adults (≥ 18 years of age) with infections caused by susceptible isolates of the designated microorganisms in the conditions listed below [see dosage and administration (2) and use in specific populations (8.5)] . culture and susceptibility testing  

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avpak - nortriptyline hydrochloride (unii: 00fn6ih15d) (nortriptyline - unii:bl03sy4lxb) - nortriptyline 10 mg - nortriptyline hydrochloride is indicated for the relief of symptoms of depression. endogenous depressions are more likely to be alleviated than are other depressive states. the use of maois intended to treat psychiatric disorders with nortriptyline hydrochloride or within 14 days of stopping treatment with nortriptyline hydrochloride is contraindicated because of an increased risk of serotonin syndrome. the use of nortriptyline hydrochloride within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated ( see warnings and dosage and administration ). starting nortriptyline hydrochloride 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 warnings and dosage and administration ). cross-sensitivity between nortriptyline hydrochloride and other dibenzazepines is a possibility. nortriptyline hydrochloride is contraindicated during the acute recovery period after myocardial infarction.

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avpak - naproxen sodium (unii: 9tn87s3a3c) (naproxen - unii:57y76r9atq) - naproxen sodium 275 mg - naproxen sodium tablets are indicated for: the relief of the signs and symptoms of: - rheumatoid arthritis - osteoarthritis - ankylosing spondylitis - polyarticular juvenile idiopathic arthritis naproxen sodium tablets are also indicated for: the relief of signs and symptoms of: - tendonitis - bursitis - acute gout the management of: - pain - primary dysmenorrhea naproxen sodium is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen or any components of the drug product [see warnings and precautions (5.7, 5.9)] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7, 5.8)] - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions ( 5.1)] risk summary use of nsaids, including naproxen sodium, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. avoid use of nsaids, including naproxen sodium, in pregnant women starting at 30 weeks of gestation (third trimester). there are no adequate and well-controlled studies of naproxen sodium in pregnant women. data from observational studies regarding potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in the general u.s. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2% to 4% for major malformations, and 15% to 20% for pregnancy loss. in animal reproduction studies in rats, rabbits, and mice no evidence of teratogenicity or fetal harm when naproxen was administered during the period of organogenesis at doses 0.13, 0.26, and 0.6 times the maximum recommended human daily dose of 1,500 mg/day, respectively [see data] . based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as naproxen, resulted in increased pre- and post-implantation loss. clinical considerations labor or delivery there are no studies on the effects of naproxen sodium during labor or delivery. in animal studies, nsaids, including naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data there is some evidence to suggest that when inhibitors of prostaglandin synthesis are used to delay preterm labor, there is an increased risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus, and intracranial hemorrhage. naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction, and abnormal prostaglandin e levels in preterm infants. because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly starting at 30-weeks of gestation, or third trimester) should be avoided. anim al data reproduction studies have been performed in rats at 20 mg/kg/day (0.13 times the maximum recommended human daily dose of 1,500 mg/day based on body surface area comparison), rabbits at 20 mg/kg/day (0.26 times the maximum recommended human daily dose, based on body surface area comparison), and mice at 170 mg/kg/day (0.6 times the maximum recommended human daily dose based on body surface area comparison) with no evidence of impaired fertility or harm to the fetus due to the drug. based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as naproxen, resulted in increased pre- and post-implantation loss. risk summary the naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for naproxen sodium and any potential adverse effects on the breastfed infant from the naproxen sodium or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including naproxen sodium, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including naproxen sodium, in women who have difficulties conceiving or who are undergoing investigation of infertility. safety and effectiveness in pediatric patients below the age of 2 years have not been established. pediatric dosing recommendations for polyarticular juvenile idiopathic arthritis are based on well-controlled studies [see dosage and administration (2)] . there are no adequate effectiveness or dose-response data for other pediatric conditions, but the experience in polyarticular juvenile idiopathic arthritis and other use experience have established that single doses of 2.5 to 5 mg/kg as naproxen suspension, , with total daily dose not exceeding 15 mg/kg/day, are well tolerated in pediatric patients over 2 years of age. the hepatic and renal tolerability of long-term naproxen administration was studied in two double-blind clinical trials involving 586 patients. of the patients studied, 98 patients were age 65 and older and 10 of the 98 patients were age 75 and older. naproxen was administered at doses of 375 mg twice daily or 750 mg twice daily for up to 6 months. transient abnormalities of laboratory tests assessing hepatic and renal function were noted in some patients, although there were no differences noted in the occurrence of abnormal values among different age groups. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see warnings and precautions (5.1, 5.2, 5.3, 5.6, 5.13)]. studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. the clinical significance of this finding is unclear, although it is possible that the increase in free naproxen concentration could be associated with an increase in the rate of adverse events per a given dosage in some elderly patients. caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. as with other drugs used in the elderly, it is prudent to use the lowest effective dose. experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nonsteroidal anti-inflammatory drugs. elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. most spontaneous reports of fatal gi events are in the geriatric population [see warnings and precautions (5.2)] . naproxen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see clinical pharmacology (12.3)] . geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nonsteroidal anti-inflammatory drugs [see warnings and precautions (5.6)] . caution is advised when high doses are required and some adjustment of dosage may be required in these patients. it is prudent to use the lowest effective dose [see clinical pharmacology (12.3)] . naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 ml/min) [see warnings and precautions (5.6), clinical pharmacology (12.3)] .

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avpak - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 125 mg -   divalproex sodium delayed-release capsules (sprinkle) are indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. divalproex sodium delayed-release capsules (sprinkle) are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.    simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. complex absence is the term used when other signs are also present. because of the risk to the fetus of decreased iq, neural tube defects, and other major congenital malformations, which may occur very early in pregnancy, valproate should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition [see warnings and precautions (5.2, 5.3, 5.4), use in specific populations (8.1), and patient counseling information (17)]. - divalproex sodium delayed-release capsules (sprinkle) should not be administered to patients with hepatic disease or significant hepatic dysfunction [see warnings and precautions (5.1) ]. - divalproex sodium delayed-release capsules (sprinkle) are contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial dna polymerase γ (polg; e.g., alpers-huttenlocher syndrome) and children under two years of age who are suspected of having a polg-related disorder [see warnings and precautions (5.1) ]. - divalproex sodium delayed-release capsules (sprinkle) are contraindicated in patients with known hypersensitivity to the drug [see warnings and precautions (5.12) ]. - divalproex sodium delayed-release capsules (sprinkle) are contraindicated in patients with known urea cycle disorders [see warnings and precautions (5.6) ]. pregnancy category d for epilepsy [see warnings and precautions (5.2, 5.3) ]. pregnancy registry to collect information on the effects of in utero exposure to divalproex sodium, physicians should encourage pregnant patients taking divalproex sodium to enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling toll free 1-888-233-2334, and must be done by the patients themselves. information on the registry can be found at the website, http://www.aedpregnancyregistry.org/. fetal risk summary all pregnancies have a background risk of birth defects (about 3%), pregnancy loss (about 15%), or other adverse outcomes regardless of drug exposure. maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects, but also malformations involving other body systems (e.g., craniofacial defects, cardiovascular malformations, hypospadias, limb malformations). 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 (5.3) ]. several published epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores than children exposed to either another antiepileptic drug in utero or to no antiepileptic drugs in utero [see warnings and precautions (5.3) ]. an observational study has suggested that exposure to valproate products during pregnancy may increase 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. because the study was observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder cannot be considered definitive. in animal studies, offspring with prenatal exposure to valproate had structural malformations similar to those seen in humans and demonstrated neuro behavioral deficits. clinical considerations - neural tube defects are the congenital malformation most strongly associated with maternal valproate use. the risk of spina bifida following in utero valproate exposure is generally estimated as 1 to 2%, compared to an estimated general population risk for spina bifida of about 0.06 to 0.07% (6 to 7 in 10,000 births). - valproate can cause decreased iq scores in children whose mothers were treated with valproate during pregnancy. - because of the risks of decreased iq, neural tube defects, and other fetal adverse events, which may occur very early in pregnancy: - valproate should not be administered to a woman of childbearing potential unless the drug is essential to the management of her medical condition. this is especially important when valproate use is considered for a condition not usually associated with permanent injury or death (e.g., migraine). - divalproex sodium delayed-release capsules (sprinkle) should not be used to treat women with epilepsy who are pregnant or who plan to become pregnant unless other treatments have failed to provide adequate symptom control or are otherwise unacceptable. in such women, the benefits of treatment with valproate during pregnancy may still outweigh the risks. when treating a pregnant woman or a woman of childbearing potential, carefully consider both the potential risks and benefits of treatment and provide appropriate counseling. - 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. 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. - 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. - 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 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%. the risk of spina bifida following in utero valproate exposure has been estimated to be approximately 1 to 2%. 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 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 antiepileptic drugs taken in 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 malformations of varying severity involving other body systems. published epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores than children exposed to either another antiepileptic drug in utero or to no antiepileptic drugs in utero . the largest of these studies 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 to110]), 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 antiepileptic drugs throughout pregnancy, whether the risk for decreased iq was related to a particular time period during pregnancy could not be assessed. although all of 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 cognitive development. 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 treatment of pregnant animals with valproate during organogenesis at clinically relevant doses (calculated on a body surface area 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. valproate is excreted in human milk. caution should be exercised when valproate is administered to a nursing woman. 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 , warning and precautions (5.1)]. when divalproex sodium is used in this patient group, it should be used with extreme caution and as a sole agent. the benefits of therapy should be weighed against the risks. above the age of 2 years, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups. younger children, especially those receiving enzyme inducing drugs, will require larger maintenance doses to attain targeted total and unbound valproate concentrations. pediatric patients (i.e., between 3 months and 10 years) have 50% higher clearances expressed on weight (i.e., ml/min/kg) than do adults. over the age of 10 years, children have pharmacokinetic parameters that approximate those of adults. the variability in free fraction limits the clinical usefulness of monitoring total serum valproic acid concentrations. interpretation of valproic acid concentrations in children should include consideration of factors that affect hepatic metabolism and protein binding. pediatric clinical trials divalproex sodium was studied in seven pediatric clinical trials. two of the pediatric studies were doubleblinded placebo-controlled trials to evaluate the efficacy of divalproex sodium extended-release tablets for the indications of mania (150 patients aged 10 to 17 years, 76 of whom were on divalproex sodium extended-release tablets) and migraine (304 patients aged 12 to 17 years, 231 of whom were on divalproex sodium extended-release tablets). efficacy was not established for either the treatment of migraine or the treatment of mania. the most common drug-related adverse reactions (reported > 5% and twice the rate of placebo) reported in the controlled pediatric mania study were nausea, upper abdominal pain, somnolence, increased ammonia, gastritis and rash. the remaining five trials were long term safety studies. two six month pediatric studies were conducted to evaluate the long-term safety of divalproex sodium extended-release tablets for the indication of mania (292 patients aged 10 to 17 years). two twelve month pediatric studies were conducted to evaluate the long-term safety of divalproex sodium extended-release tablets for the indication of migraine (353 patients aged 12 to 17 years). one twelve month study was conducted to evaluate the safety of divalproex sodium delayed-release capsules (sprinkle) in the indication of partial seizures (169 patients aged 3 to 10 years). in these seven clinical trials, the safety and tolerability of divalproex sodium in pediatric patients were shown to be comparable to those in adults [see adverse reactions (6)]. juvenile animal toxicology in studies of valproate in immature animals, toxic effects not observed in adult animals included retinal dysplasia in rats treated during the neonatal period (from postnatal day 4) and nephrotoxicity in rats treated during the neonatal and juvenile (from postnatal day 14) periods. the no-effect dose for these findings was less than the maximum recommended human dose on a mg/m 2 basis. no patients above the age of 65 years were enrolled in doubleblind prospective clinical trials of mania associated with bipolar illness. in a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. a higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. discontinuation of valproate was occasionally associated with the latter two events. it is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients. a study of elderly patients with dementia revealed drug related somnolence and discontinuation for somnolence [see warnings and precautions (5.14) ]. the starting dose should be reduced in these patients, and dosage reductions or discontinuation should be considered in patients with excessive somnolence [see dosage and administration (2.2) ]. the capacity of elderly patients (age range: 68 to 89 years) to eliminate valproate has been shown to be reduced compared to younger adults (age range: 22 to 26 years) [see clinical pharmacology (12.3) ]. liver disease liver disease impairs the capacity to eliminate valproate [see boxed warning, contraindications (4), warnings and precautions (5.1), and clinical pharmacology (12.3)].

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avpak - bupropion hydrochloride (unii: zg7e5poy8o) (bupropion - unii:01zg3tpx31) - bupropion hydrochloride 300 mg - bupropion hydrochloride extended-release tablets (xl) are indicated for the treatment of major depressive disorder (mdd), as defined by the diagnostic and statistical manual (dsm). the efficacy of the immediate-release formulation of bupropion was established in two 4-week controlled inpatient trials and one 6-week controlled outpatient trial of adult patients with mdd. the efficacy of the sustained-release formulation of bupropion in the maintenance treatment of mdd was established in a long-term (up to 44 weeks), placebo-controlled trial in patients who had responded to bupropion in an 8-week study of acute treatment [see clinical studies (14.1) ]. bupropion hydrochloride extended-release tablets (xl) are indicated for the prevention of seasonal major depressive episodes in patients with a diagnosis of seasonal affective disorder (sad). the efficacy of bupropion hydrochloride extended-release tablets in the prevention of seasonal major depressive episodes was established in 3 placebo-controlled trials in adult outpatients with a history of mdd with an autumn-winter seasonal pattern as defined in the dsm [see clinical studies (14.2) ]. - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients with seizure disorder. - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients with a current or prior diagnosis of bulimia or anorexia nervosa as a higher incidence of seizures was observed in such patients treated with bupropion hydrochloride extended-release tablets (xl) [see warnings and precautions (5.3)] . - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see warnings and precautions (5.3) and drug interactions (7.3)]. - the use of maois (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride extended-release tablets (xl) or within 14 days of discontinuing treatment with bupropion hydrochloride extended-release tablets (xl) is contraindicated. there is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (xl) are used concomitantly with maois. the use of bupropion hydrochloride extended-release tablets (xl) within 14 days of discontinuing treatment with an maoi is also contraindicated. starting bupropion hydrochloride extended-release tablets (xl) in a patient treated with reversible maois such as linezolid or intravenous methylene blue is contraindicated [see dosage and administration (2.9), warnings and precautions (5.4) and drug interactions (7.6)]. - bupropion hydrochloride extended-release tablets (xl) are contraindicated in patients with known hypersensitivity to bupropion or other ingredients of bupropion hydrochloride extended-release tablets (xl). anaphylactoid/anaphylactic reactions and stevens-johnson syndrome have been reported [see warnings and precautions (5.8)]. pregnancy category c risk summary data from epidemiological studies including pregnant women exposed to bupropion in the first trimester indicate no increased risk of congenital malformations overall. all pregnancies regardless of drug exposure have a background rate of 2% to 4% for major malformations and 15% to 20% for pregnancy loss. no clear evidence of teratogenic activity was found in reproductive developmental studies conducted in rats and rabbits. however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at doses approximately equal to the maximum recommended human dose (mrhd) and greater and decreased fetal weights were seen at doses twice the mrhd and greater. bupropion hydrochloride extended-release tablets (xl) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. clinical considerations consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medications during pregnancy and postpartum. human data data from an international bupropion pregnancy registry (675 first trimester exposures) and a retrospective cohort study using the united healthcare database (1,213 first trimester exposures) did not show an increased risk for malformations overall. no increased risk for cardiovascular malformations overall has been observed after bupropion exposure during the first trimester. the prospectively observed rate of cardiovascular malformations in pregnancies with exposure to bupropion in the first trimester from the international pregnancy registry was 1.3% (9 cardiovascular malformations/675 first-trimester maternal bupropion exposures), which is similar to the background rate of cardiovascular malformations (approximately 1%). data from the united healthcare database and a case-controlled study (6,853 infants with cardiovascular malformations and 5,753 with non-cardiovascular malformations) from the national birth defects prevention study (nbdps) did not show an increased risk for cardiovascular malformations overall after bupropion exposure during the first trimester. study findings on bupropion exposure during the first trimester and risk left ventricular outflow tract obstruction (lvoto) are inconsistent and do not allow conclusions regarding possible association. the united healthcare database lacked sufficient power to evaluate this association; the nbdps found increased risk for lvoto (n = 10; adjusted or = 2.6; 95% ci 1.2, 5.7) and the slone epidemiology case control study did not find increased risk for lvoto. study findings on bupropion exposure during the first trimester and risk for ventricular septal defect (vsd) are inconsistent and do not allow conclusions regarding a possible association. the slone epidemiology study found an increased risk for vsd following first trimester maternal bupropion exposure (n = 17; adjusted or = 2.5; 95% ci: 1.3, 5.0) but did not find an increased risk for any other cardiovascular malformations studied (including lvoto as above). the nbdps and united healthcare database study did not find an association between first trimester maternal bupropion exposure and vsd. for the findings of lvoto and vsd, the studies were limited by the small number of exposed cases, inconsistent findings among studies, and the potential for chance findings from multiple comparisons in case control studies. animal data in studies conducted in rats and rabbits, bupropion was administered orally at doses of up to 450 and 150 mg/kg/day, respectively (approximately 11 and 7 times the mrhd, respectively, on a mg/m 2 basis), during the period of organogenesis. no clear evidence of teratogenic activity was found in either species; however, in rabbits, slightly increased incidences of fetal malformations and skeletal variations were observed at the lowest dose tested (25 mg/kg/day, approximately equal to the mrhd on a mg/m 2 basis) and greater. decreased fetal weights were observed at 50 mg/kg and greater. when rats were administered bupropion at oral doses of up to 300 mg/kg/day (approximately 7 times the mrhd on a mg/m 2 basis) prior to mating and throughout pregnancy and lactation, there were no apparent adverse effects on offspring development. bupropion and its metabolites are present in human milk. in a lactation study of ten women, levels of orally dosed bupropion and its active metabolites were measured in expressed milk. the average daily infant exposure (assuming 150 ml/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. exercise caution when bupropion hydrochloride extended-release tablets (xl) are administered to a nursing woman. safety and effectiveness in the pediatric population have not been established. when considering the use of bupropion hydrochloride extended-release tablets (xl) in a child or adolescent, balance the potential risks with the clinical need [see boxed warning and warnings and precautions (5.1)]. of the approximately 6,000 patients who participated in clinical trials with bupropion hydrochloride sustained-release tablets (depression and smoking cessation studies), 275 were ≥65 years old and 47 were ≥75 years old. in addition, several hundred patients ≥65 years of age participated in clinical trials using the immediate-release formulation of bupropion hydrochloride (depression studies). no overall differences in safety or effectiveness were observed between these subjects and younger subjects. reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. the risk of adverse reactions may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, it may be necessary to consider this factor in dose selection; it may be useful to monitor renal function [see dosage and administration (2.7), use in specific populations (8.6), and clinical pharmacology (12.3)]. consider a reduced dose and/or dosing frequency of bupropion hydrochloride extended-release tablets (xl) in patients with renal impairment (glomerular filtration rate: <90 ml/min). bupropion and its metabolites are cleared renally and may accumulate in such patients to a greater extent than usual. monitor closely for adverse reactions that could indicate high bupropion or metabolite exposures [see dosage and administration (2.7) and clinical pharmacology (12.3)]. in patients with moderate to severe hepatic impairment (child-pugh score: 7 to 15), the maximum bupropion hydrochloride extended-release tablets (xl) dose is 150 mg every other day. in patients with mild hepatic impairment (child-pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see dosage and administration (2.6) and clinical pharmacology (12.3)]. bupropion is not a controlled substance. humans controlled clinical studies of bupropion hcl immediate-release conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed patients demonstrated an increase in motor activity and agitation/excitement. in a population of individuals experienced with drugs of abuse, a single dose of 400 mg bupropion produced mild amphetamine-like activity as compared to placebo on the morphine-benzedrine subscale of the addiction research center inventories (arci), and a score intermediate between placebo and amphetamine on the liking scale of the arci. these scales measure general feelings of euphoria and drug desirability. findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs. nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or cns stimulant abusers. however, higher doses (that could not be tested because of the risk of seizure) might be modestly attractive to those who abuse cns stimulant drugs. bupropion hydrochloride extended-release tablets are intended for oral use only. the inhalation of crushed tablets or injection of dissolved bupropion has been reported. seizures and/or cases of death have been reported when bupropion has been administered intranasally or by parenteral injection. animals studies in rodents and primates demonstrated that bupropion exhibits some pharmacologic actions common to psychostimulants. in rodents, it has been shown to increase locomotor activity, elicit a mild stereotyped behavioral response, and increase rates of responding in several schedule-controlled behavior paradigms. in primate models assessing the positive reinforcing effects of psychoactive drugs, bupropion was self-administered intravenously. in rats, bupropion produced amphetamine-like and cocaine-like discriminative stimulus effects in drug discrimination paradigms used to characterize the subjective effects of psychoactive drugs.

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

avpak - ursodiol (unii: 724l30y2qr) (ursodiol - unii:724l30y2qr) - ursodiol 300 mg - - ursodiol is indicated for patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. safety of use of ursodiol beyond 24 months is not established. - ursodiol is indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss. - ursodiol will not dissolve calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones. hence, patients with such stones are not candidates for ursodiol therapy. - patients with compelling reasons for cholecystectomy including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula are not candidates for ursodiol therapy. - allergy to bile acids.

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

avpak - dutasteride (unii: o0j6xjn02i) (dutasteride - unii:o0j6xjn02i) - dutasteride 0.5 mg - dutasteride capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to: •  improve symptoms, •  reduce the risk of acute urinary retention (aur), and •  reduce the risk of the need for bph-related surgery.  dutasteride in combination with the alpha adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic bph in men with an enlarged prostate.  dutasteride is not approved for the prevention of prostate cancer.  dutasteride is contraindicated for use in: •        pregnancy. in animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. therefore, dutasteride may cause fetal harm when administered to a pregnant woman. if dutasteride is used during pregnancy or if the patient becomes pregnant while taking dutasteride, the patient should be apprised of the potential hazard to the fetus [see warnings and precautions (5.4), use in specific populations ( 8.1)] . •