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alembic pharmaceuticals inc. - 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)] .  pregnancy category c there are no adequate and well-controlled studies of modafinil in pregnant women. intrauterine growth restriction and spontaneous abortion have been reported in association with modafinil (a mixture of r-and s-modafinil) and arm

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golden state medical supply, inc. - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - duloxetine delayed-release capsules is indicated for the treatment of: - major depressive disorder in adults - generalized anxiety disorder in adults and pediatric patients 7 years of age and older - diabetic peripheral neuropathic pain in adults - fibromyalgia in adults and pediatric patients 13 years of age and older - chronic musculoskeletal pain in adults the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is contraindicated [see dosage and administration (2.8)and warnings and precautions (5.4)]. starting duloxetine delayed-release capsules in a patient who is being treated with maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see dosage and administration (2.9)and warnings and precautions (5.4)]. risk summary data from a postmarketing retrospective cohort study indicate that use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage. data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes (see data) . there are risks associated with untreated depression and fibromyalgia in pregnancy, and with exposure to snris and ssris, including duloxetine delayed-release capsules, during pregnancy (see clinical considerations). in rats and rabbits treated with duloxetine during the period of organogenesis, fetal weights were decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the maximum recommended human dose (mrhd) of 120 mg/day given to adolescents on a mg/m 2 basis. when duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the mrhd given to adolescents on a mg/m 2 basis. at this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. post-weaning growth was not adversely affected. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis. it is not known if these adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors. maternal adverse reactions use of duloxetine in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see warnings and precautions (5.5)]. fetal/neonatal adverse reaction neonates exposed to duloxetine delayed-release capsules and other snris or ssris late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. such complications can arise immediately upon delivery. reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. these findings are consistent with either a direct toxic effect of the snris or ssris, or possibly, a drug discontinuation syndrome. it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see warnings and precautions (5.4)]. data human data data from a postmarketing retrospective claims-based cohort study found an increased risk for postpartum hemorrhage among 955 pregnant women exposed to duloxetine in the last month of pregnancy compared to 4,128,460 unexposed pregnant women (adjusted relative risk: 1.53; 95% ci: 1.08-2.18). the same study did not find a clinically meaningful increase in the risk for major birth defects in the comparison of 2532 women exposed to duloxetine in the first trimester of pregnancy to 1,284,827 unexposed women after adjusting for several confounders. methodologic limitations include possible residual confounding, misclassification of exposure and outcomes, lack of direct measures of disease severity, and lack of information about alcohol use, nutrition, and over-the-counter medication exposures. animal data in animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development. when duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of malformations or developmental variations at doses up to 45 mg/kg/day [3 and 6 times, respectively, the mrhd of 120 mg/day given to adolescents on a mg/m 2 basis]. however, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day (approximately equal to the mrhd in rats and 2 times the mrhd in rabbits). when duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (2 times the mrhd given to adolescents on a mg/m 2 basis); the no-effect dose was 10 mg/kg/day. furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment. risk summary data from published literature report the presence of duloxetine in human milk (see data) . there are reports of sedation, poor feeding, and poor weight gain in infants exposed to duloxetine through breast milk (see clinical considerations). there are no data on the effect of duloxetine on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for duloxetine delayed-release capsules and any potential adverse effects on the breastfed child from duloxetine delayed-release capsules or from the underlying maternal condition. clinical considerations infants exposed to duloxetine delayed-release capsules should be monitored for sedation, poor feeding and poor weight gain. data disposition of duloxetine delayed-release capsules was studied in 6 lactating women who were at least 12 weeks postpartum and had elected to wean their infants. the women were given 40 mg of duloxetine delayed-release capsules twice daily for 3.5 days. the peak concentration measured in breast milk occurred at a median of 3 hours after the dose. the amount of duloxetine in breast milk was approximately 7 mcg/day while on that dose; the estimated daily infant dose was approximately 2 mcg/kg/day, which is less than 1% of the maternal dose. the presence of duloxetine metabolites in breast milk was not examined. the safety and effectiveness of duloxetine delayed-release capsules have been established for treatment of generalized anxiety disorder (gad) in patients 7 to 17 years of age and for treatment of juvenile fibromyalgia syndrome in patients 13 to 17 years of age. the safety and effectiveness of duloxetine delayed-release capsules have not been established in pediatric patients with major depressive disorder (mdd), diabetic peripheral neuropathic pain, or chronic musculoskeletal pain. antidepressants increased the risk of suicidal thoughts and behavior in pediatric patients. monitor all pediatric patients being treated with antidepressants for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of treatment, or at times of dosage changes [see warnings and precautions (5.1)] . perform regular monitoring of weight and growth in pediatric patients treated with duloxetine delayed-release capsules [see adverse reactions (6.1)]. generalized anxiety disorder use of duloxetine delayed-release capsules for the treatment of gad in patients 7 to 17 years of age is supported by one 10-week, placebo- controlled trial (gad-6). the study included 272 pediatric patients with gad of which 47% were 7 to 11 years of age (53% were 12 to 17 years of age). duloxetine delayed-release capsules demonstrated superiority over placebo as measured by greater improvement in the pediatric anxiety rating scale (pars) for gad severity score [see clinical studies (14.3)]. the safety and effectiveness of duloxetine delayed-release capsules for the treatment of gad in pediatric patients less than 7 years of age have not been established. fibromyalgia use of duloxetine delayed-release capsules for treatment of fibromyalgia in patients 13 to 17 years of age is supported by a 13-week placebo- controlled trial in 184 patients with juvenile fibromyalgia syndrome (study fm-4). duloxetine delayed-release capsules showed improvement over placebo on the primary endpoint, change from baseline to end-of-treatment on the brief pain inventory (bpi) – modified short form: adolescent version 24-hour average pain severity rating [see clinical studies (14.5)] . the safety and effectiveness of duloxetine delayed-release capsules for the treatment of fibromyalgia in patients less than 13 years of age have not been established. major depressive disorder the safety and effectiveness of duloxetine delayed-release capsules have not been established in pediatric patients for the treatment of mdd. efficacy of duloxetine delayed-release capsules was not demonstrated in two 10-week, placebo-controlled trials with 800 pediatric patients aged 7 to 17 years old with mdd (mdd-6 and mdd-7). neither duloxetine delayed-release capsules nor an active control (approved for treatment of pediatric mdd) was superior to placebo. the most frequently observed adverse reactions in the mdd pediatric clinical trials included nausea, headache, decreased weight, and abdominal pain. decreased appetite and weight loss have been observed in association with the use of ssris and snris. juvenile animal toxicology data duloxetine administration to young rats from post-natal day 21 (weaning) through post-natal day 90 (adult) resulted in decreased body weights that persisted into adulthood, but recovered when drug treatment was discontinued; slightly delayed (~1.5 days) sexual maturation in females, without any effect on fertility; and a delay in learning a complex task in adulthood, which was not observed after drug treatment was discontinued. these effects were observed at the high dose of 45 mg/kg/day (2 times the mrhd, for a child); the no-effect-level was 20 mg/kg/day (≈1 times the mrhd, for a child). geriatric exposure in premarketing clinical trials of duloxetine delayed-release capsules - of the 2,418 patients in mdd trials, 6% (143) were 65 years of age or over. - of the 1,041 patients in clbp trials, 21% (221) were 65 years of age or over. - of the 487 patients in oa trials, 41% (197) were 65 years of age or over. - of the 1,074 patients in the dpnp trials, 33% (357) were 65 years of age or over. - of the 1,761 patients in fm trials, 8% (140) were 65 years of age or over. in the mdd, gad, dpnp, fm, oa, and clbp studies, no overall differences in safety or effectiveness were generally observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between these geriatric and younger adult patients, but greater sensitivity of some older patients cannot be ruled out. ssris and snris, including duloxetine delayed-release capsules have been associated with clinically significant hyponatremia in geriatric patients, who may be at greater risk for this adverse reaction [see warnings and precautions (5.13)]. in an analysis of data from all placebo-controlled-trials, duloxetine delayed-release capsules-treated patients reported a higher rate of falls compared to placebo-treated patients. the increased risk appears to be proportional to a patient's underlying risk for falls. underlying risk appears to increase steadily with age. as geriatric patients tend to have a higher prevalence of risk factors for falls such as medications, medical comorbidities and gait disturbances, the impact of increasing age by itself on falls during duloxetine delayed-release capsules treatment is unclear. falls with serious consequences including bone fractures and hospitalizations have been reported with duloxetine delayed-release capsules use [see warnings and precautions (5.3)and adverse reactions (6.1)]. the pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females (65 to 77 years) and healthy middle-age females (32 to 50 years). there was no difference in the c max , but the auc of duloxetine was somewhat (about 25%) higher and the half-life about 4 hours longer in the elderly females. population pharmacokinetic analyses suggest that the typical values for clearance decrease by approximately 1% for each year of age between 25 to 75 years of age; but age as a predictive factor only accounts for a small percentage of between-patient variability. dosage adjustment based on the age of the adult patient is not necessary. duloxetine's half-life is similar in men and women. dosage adjustment based on gender is not necessary. duloxetine bioavailability (auc) appears to be reduced by about one-third in smokers. dosage modifications are not recommended for smokers. no specific pharmacokinetic study was conducted to investigate the effects of race. patients with clinically evident hepatic impairment have decreased duloxetine metabolism and elimination. after a single 20 mg dose of duloxetine delayed-release capsules, 6 cirrhotic patients with moderate liver impairment (child-pugh class b) had a mean plasma duloxetine clearance about 15% that of age- and gender-matched healthy subjects, with a 5-fold increase in mean exposure (auc). although c max was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see dosage and administration (2.7)and warnings and precautions (5.14)]. limited data are available on the effects of duloxetine in patients with end-stage renal disease (esrd). after a single 60 mg dose of duloxetine, c max and auc values were approximately 100% greater in patients with esrd receiving chronic intermittent hemodialysis than in subjects with normal renal function. the elimination half-life, however, was similar in both groups. the aucs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6- methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing. population pk analyses suggest that mild to moderate degrees of renal impairment (estimated crcl 30-80 ml/min) have no significant effect on duloxetine apparent clearance [see dosage and administration (2.7)and warnings and precautions (5.14)]. in animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential. while duloxetine delayed-release capsules have not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. however, it is not possible to predict on the basis of premarketing experience the extent to which a cns active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of duloxetine delayed-release capsules (e.g., development of tolerance, incrementation of dose, drug-seeking behavior). in drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats.

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hospira, inc. - bupivacaine hydrochloride (unii: 7tqo7w3vt8) (bupivacaine - unii:y8335394ro) - bupivacaine hydrochloride anhydrous 2.5 mg in 1 ml - marcaine / marcaine with epinephrine is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. specific concentrations and presentations of marcaine / marcaine with epinephrine are recommended for each type of block indicated to produce local or regional anesthesia or analgesia [see dosage and administration (2.2)]. limitations of use not all blocks are indicated for use with marcaine / marcaine with epinephrine given clinically significant risks associated with use [see dosage and administration (2.2), contraindications (4), warnings and precautions (5.1, 5.4, 5.5, 5.7, 5.9)] . marcaine / marcaine with epinephrine is contraindicated in: risk summary marcaine / marcaine with epinephrine is contraindicated for obstetrical paracervical block anesthesia. its use in this technique has resulted in fetal bradycardia and death [see contraindications (4), warnings and precautions (5.1)] . there are no available data on use of marcaine / marcaine with epinephrine in pregnant women to inform a drug-associated risk of adverse developmental outcomes. in animal studies, embryo-fetal lethality was noted when bupivacaine was administered subcutaneously to pregnant rabbits during organogenesis at clinically relevant doses. decreased pup survival was observed in a rat pre- and post-natal developmental study (dosing from implantation through weaning) at a dose level comparable to the daily maximum recommended human dose (mrhd) on a body surface area (bsa) basis. based on animal data, advise pregnant women of the potential risks to a fetus (see data). local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity [see clinical pharmacology (12.3)]. the incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. adverse reactions in the parturient, fetus, and neonate involve alterations of the cns, peripheral vascular tone, and cardiac function. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. 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 maternal adverse reactions maternal hypotension has resulted from regional anesthesia. local anesthetics produce vasodilation by blocking sympathetic nerves. the supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus. therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels be accomplished. elevating the patient's legs will also help prevent decreases in blood pressure. the fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable. labor or delivery epidural, caudal, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. epidural anesthesia has been reported to prolong the second stage of labor by removing the parturient's reflex urge to bear down or by interfering with motor function. the use of obstetrical anesthesia may increase the need for forceps assistance. the use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. this has not been reported with bupivacaine. it is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to parturients. to do this, the patient must be maintained in the left lateral decubitus position or a blanket roll or sandbag may be placed beneath the right hip and gravid uterus displaced to the left. data animal data bupivacaine hydrochloride produced developmental toxicity when administered subcutaneously to pregnant rats and rabbits at clinically relevant doses. bupivacaine hydrochloride was administered subcutaneously to rats at doses of 4.4, 13.3, & 40 mg/kg and to rabbits at doses of 1.3, 5.8, & 22.2 mg/kg during the period of organogenesis (implantation to closure of the hard palate). the high doses are comparable to the daily mrhd of 400 mg/day on a mg/m2 bsa basis. no embryo-fetal effects were observed in rats at the high dose which caused increased maternal lethality. an increase in embryo-fetal deaths was observed in rabbits at the high dose in the absence of maternal toxicity with the fetal no observed adverse effect level representing approximately 0.3 times the mrhd on a bsa basis. in a rat pre- and post-natal developmental study (dosing from implantation through weaning) conducted at subcutaneous doses of 4.4, 13.3, & 40 mg/kg, decreased pup survival was observed at the high dose. the high dose is comparable to the daily mrhd of 400 mg/day on a bsa basis. risk summary lactation studies have not been conducted with bupivacaine. bupivacaine has been reported to be excreted in human milk suggesting that the nursing infant could be theoretically exposed to a dose of the drug. marcaine / marcaine with epinephrine should be administered to lactating women only if clearly indicated. studies assessing the effects of marcaine / marcaine with epinephrine in breastfed children have not been performed. studies to assess the effect of marcaine / marcaine with epinephrine on milk production or excretion have not been performed. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for bupivacaine and any potential adverse effects on the breastfed child from bupivacaine or from the underlying maternal condition. marcaine / marcaine with epinephrine is approved for use in adults. administration of marcaine / marcaine with epinephrine in pediatric patients younger than 12 years is not recommended. continuous infusions of bupivacaine in pediatric patients have been reported to result in high systemic levels of bupivacaine and seizures; high plasma levels may also be associated with cardiovascular abnormalities. patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with marcaine / marcaine with epinephrine. in clinical studies of bupivacaine, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger adult patients. differences in various pharmacokinetic parameters have been observed between elderly and younger adult patients [see clinical pharmacology (12.3)] . this product 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. elderly patients may require lower doses of marcaine / marcaine with epinephrine. amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. patients with severe hepatic impairment, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. therefore, consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment treated with marcaine / marcaine with epinephrine, especially with repeat doses [see warnings and precautions (5.10)] . bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. this should be considered when selecting the marcaine / marcaine with epinephrine dosage [see use in specific populations (8.5)] .

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torrent pharmaceuticals limited - quetiapine fumarate (unii: 2s3pl1b6uj) (quetiapine - unii:bgl0jsy5si) - quetiapine 25 mg - quetiapine tablets are indicated for the treatment of schizophrenia. the efficacy of quetiapine tablets in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents (13 to 17 years). the effectiveness of quetiapine tablets for the maintenance treatment of schizophrenia has not been systematically evaluated in controlled clinical trials [ see clinical studies ( 14.1) ]. quetiapine tablets are indicated for the acute treatment of manic episodes associated with bipolar i disorder, both as monotherapy and as an adjunct to lithium or divalproex. efficacy was established in two 12-week monotherapy trials in adults, in one 3-week adjunctive trial in adults, and in one 3-week monotherapy trial in pediatric patients (10 to 17 years) [see clinical studies ( 14.2)]. quetiapine tablets are indicated as monotherapy for the acute treatment of depressive episodes associated with bipolar disorder. efficacy w

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sumitomo pharma america, inc. - lurasidone hydrochloride (unii: o0p4i5851i) (lurasidone - unii:22ic88528t) - lurasidone hydrochloride 20 mg - latuda is indicated for: - treatment of adult and adolescent patients (13 to 17 years) with schizophrenia [see clinical studies (14.1)] . - monotherapy treatment of adult and pediatric patients (10 to 17 years) with major depressive episode associated with bipolar i disorder (bipolar depression) [see clinical studies (14.2)] . - adjunctive treatment with lithium or valproate in adult patients with major depressive episode associated with bipolar i disorder (bipolar depression) [see clinical studies (14.2)] . - known hypersensitivity to lurasidone hcl or any components in the formulation. angioedema has been observed with lurasidone [see adverse reactions (6.1)] . - strong cyp3a4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see drug interactions (7.1)]. - strong cyp3a4 inducers (e.g., rifampin, avasimibe, st. john's wort, phenytoin, carbamazepine, etc.) [see drug interactions (7.1)]. pregnancy exposure registry there is a pregnancy exposu

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dispensing solutions, inc. - zolpidem tartrate (unii: wy6w63843k) (zolpidem - unii:7k383oqi23) - zolpidem tartrate 10 mg - zolpidem tartrate tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. zolpidem tartrate tablets have been shown to decrease sleep latency for up to 35 days in controlled clinical studies [see clinical studies (14)] . the clinical trials performed in support of efficacy were 4–5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment. zolpidem tartrate tablets are contraindicated in patients with known hypersensitivity to zolpidem tartrate or to any of the inactive ingredients in the formulation. observed reactions include anaphylaxis and angioedema [see warnings and precautions (5.2)] . pregnancy category c there are no adequate and well-controlled studies of zolpidem tartrate tablets in pregnant women. zolpidem tartrate tablets should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. administration of zolpidem to pregnant rats and rabbits resulted

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dr.reddy's laboratories limited - pantoprazole sodium (unii: 6871619q5x) (pantoprazole - unii:d8tst4o562) - pantoprazole 20 mg - pantoprazole sodium delayed-release tablets are indicated for: pantoprazole sodium delayed-release tablets are 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 sodium delayed-release tablets may be considered. safety of treatment beyond 8 weeks in pediatric patients has not been established.  pantoprazole sodium delayed-release tablets are 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 sodium delayed-release tablets are indicated for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison (ze) syndrome. • pantoprazole sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see warnings and precautions (5.2) , adverse reactions (6) ]. • proton pump inhibitors (ppis), including pantoprazole sodium delayed-release tablets, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7) ].  risk summary available data from published observational studies did not demonstrate an association of major malformations or other adverse pregnancy outcomes with pantoprazole. in animal reproduction studies, no evidence of adverse development outcomes was observed with pantoprazole. reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (about 88 times the recommended human dose) and rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose) with administration of pantoprazole during organogenesis in pregnant animals and have revealed no evidence of harm to the fetus due to pantoprazole in this study (see data) . a pre-and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day) were administered to pregnant females from gestation day (gd) 6 through lactation day (ld) 21. changes in bone morphology were observed in pups exposed to pantoprazole in utero and through milk during the period of lactation as well as by oral dosing from postnatal day (pnd) 4 through pnd 21 [see use in specific populations (8.4)]. there were no drug-related findings in maternal animals. advise pregnant women of the potential risk of fetal harm. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.  data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and pantoprazole use. methodological limitations of these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. in a prospective study by the european network of teratology information services, outcomes from a group of 53 pregnant women administered median daily doses of 40 mg pantoprazole were compared to a control group of 868 pregnant women who did not take any proton pump inhibitors (ppis). there was no difference in the rate of major malformations between women exposed to ppis and the control group, corresponding to a relative risk (rr) = 0.55, [95% confidence interval (ci) 0.08-3.95]. in a population-based retrospective cohort study covering all live births in denmark from 1996 to 2008, there was no significant increase in major birth defects during analysis of first trimester exposure to pantoprazole in 549 live births. a meta-analysis that compared 1,530 pregnant women exposed to ppis in at least the first trimester with 133,410 unexposed pregnant women showed no significant increases in risk for congenital malformations or spontaneous abortion with exposure to ppis (for major malformations or=1.12 ([95% ci 0.86-1.45] and for spontaneous abortions or=1.29 [95% ci 0.84-1.97]). animal data reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. the studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole.   a pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (gd) 6 through lactation day (ld) 21. on postnatal day (pnd 4) through pnd 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (auc) in humans at a dose of 40 mg). there were no drug-related findings in maternal animals. during the preweaning dosing phase (pnd 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (auc) in humans receiving the 40 mg dose) and higher doses. on pnd 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (auc) in humans at the 40 mg dose) and higher doses. the femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. there were no microscopic changes in the distal femur, proximal tibia, or stifle joints. changes in bone parameters were partially reversible following a  recovery period, with findings on pnd 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (auc) in humans at the 40 mg dose) and higher doses. risk summary pantoprazole has been detected in breast milk of a nursing mother after a single 40 mg oral dose of pantoprazole. there were no effects on the breastfed infant (see data). there are no data on pantoprazole effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pantoprazole and any potential adverse effects on the breastfed child from pantoprazole or from the underlying maternal condition. data the breast milk of a 42-year-old woman receiving 40 mg of oral pantoprazole, at 10 months postpartum, was studied for 24 hours, to demonstrate low levels of pantoprazole present in the breast milk. pantoprazole was detectable in milk only 2 and 4 hours after the dose with milk levels of approximately 36 mcg/l and 24 mcg/l, respectively. a milk-to-plasma ratio of 0.022 was observed at 2 hours after drug administration. pantoprazole was not detectable (<10 mcg/l) in milk at 6, 8 and 24 hours after the dose. the relative dose to the infant was estimated to be 7.3 mcg of pantoprazole, which is equivalent to 0.14% of the weight-adjusted maternal dose. no adverse events in the infant were reported by the mother. the safety and effectiveness of pantoprazole sodium for short-term treatment (up to eight weeks) of ee associated with gerd have been established in pediatric patients 1 year through 16 years of age. effectiveness for ee has not been demonstrated in patients less than 1 year of age. in addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age-appropriate formulation available. therefore, pantoprazole sodium is indicated for the short-term treatment of ee associated with gerd for patients 5 years and older. the safety and effectiveness of pantoprazole sodium for pediatric uses other than ee have not been established. 1 year through 16 years of age use of pantoprazole sodium in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of ee associated with gerd is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of pantoprazole sodium for treatment of ee associated with gerd in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see clinical studies (14.1) , clinical pharmacology (12.3) ]. safety of pantoprazole sodium in the treatment of ee associated with gerd in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with ee (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). the children ages 1 year to 5 years with endoscopically diagnosed ee (defined as an endoscopic hetzel-dent score ≥ 2) were treated once daily for 8 weeks with one of two dose levels of pantoprazole sodium (approximating 0.6 mg/kg or 1.2 mg/kg). all 4 of these patients with ee were healed (hetzel-dent score of 0 or 1) at 8 weeks. because ee is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic gerd were also included in these studies. patients were treated with a range of doses of pantoprazole sodium once daily for 8 weeks. for safety findings see adverse reactions (6.1). because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of pantoprazole sodium for symptomatic gerd in the pediatric population. the effectiveness of pantoprazole sodium for treating symptomatic gerd in pediatric patients has not been established. although the data from the clinical trials support use of pantoprazole sodium for the short-term treatment of ee associated with gerd in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see dosage and administration (2) ]. in a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven gerd had a median value of 2.4 l/h. following a 1.2 mg/kg equivalent dose (15 mg for ≤ 12.5 kg and 20 mg for > 12.5 to < 25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. the estimated auc for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean auc value of 6.8 mcg•hr/ml. neonates to less than one year of age pantoprazole  sodium was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. patients were enrolled if they had symptomatic gerd based on medical history and had not responded to non-pharmacologic interventions for gerd for two weeks. patients received pantoprazole sodium daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive pantoprazole sodium treatment or placebo for the subsequent four weeks in a double-blind manner. efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. there was no statistically significant difference between pantoprazole sodium and placebo in the rate of discontinuation. in this trial, the adverse reactions that were reported more commonly (difference of ≥ 4%) in the treated population compared to the placebo population were elevated ck, otitis media, rhinitis, and laryngitis. in a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with gerd compared to adults who received a single 40 mg dose (geometric mean auc was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of pantoprazole sodium, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). in these patients, the apparent clearance (cl/f) increased with age (median clearance: 0.6 l/hr, range: 0.03 to 3.2 l/hr). these doses resulted in pharmacodynamic effects on gastric but not esophageal ph. following once daily dosing of 2.5 mg of pantoprazole sodium in preterm infants and neonates, there was an increase in the mean gastric ph (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric ph was > 4 (from 60% at baseline to 80% at steady-state). following once daily dosing of approximately 1.2 mg/kg of pantoprazole sodium in infants 1 through 11 months of age, there was an increase in the mean gastric ph (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric ph was > 4 (from 32% at baseline to 60% at steady-state). however, no significant changes were observed in mean intraesophageal ph or % time that esophageal ph was < 4 in either age group. because pantoprazole sodium was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of pantoprazole sodium for treatment of symptomatic gerd in infants less than 1 year of age is not indicated. animal toxicity data in a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (auc) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (pnd 4) through pnd 21, in addition to lactational exposure through milk. on pnd 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (auc) in children aged 6 to 11 years at the 40 mg dose) and higher doses. changes in bone parameters were partially reversible following a recovery period.   in neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. an increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, was observed in the fundic mucosa of stomachs in repeated-dose studies. full to partial recovery of these effects were noted in animals of both age groups following a recovery period. in short-term u.s. clinical trials, ee healing rates in the 107 elderly patients (≥ 65 years old) treated with pantoprazole sodium were similar to those found in patients under the age of 65. the incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.

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

aurobindo pharma limited - duloxetine hydrochloride (unii: 9044sc542w) (duloxetine - unii:o5tnm5n07u) - duloxetine 20 mg - duloxetine delayed-release capsules are indicated for the treatment of: - major depressive disorder [see clinical studies (14.1)] - generalized anxiety disorder [see clinical studies (14.2)] - diabetic peripheral neuropathy [see clinical studies (14.3)] - chronic musculoskeletal pain [see clinical studies (14.5)] monoamine oxidase inhibitors (maois) — the use of maois intended to treat psychiatric disorders with duloxetine delayed-release capsules or within 5 days of stopping treatment with duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. the use of duloxetine delayed-release capsules within 14 days of stopping an maoi intended to treat psychiatric disorders is also contraindicated [see dosage and administration (2.8) and warnings and precautions (5.4)] . starting duloxetine delayed-release capsules 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 seroto

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

aurobindo pharma limited - esomeprazole magnesium dihydrate (unii: 36h71644eq) (esomeprazole - unii:n3pa6559ft) - esomeprazole 20 mg - adults esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) in the healing and symptomatic resolution of diagnostically confirmed ee in adults. for those patients who have not healed after 4 to 8 weeks of treatment, an additional 4- to 8- week course of esomeprazole magnesium delayed-release capsules may be considered. pediatric patients 12 years to 17 years of age esomeprazole magnesium delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) for the healing of ee in pediatric patients 12 years to 17 years of age. esomeprazole magnesium delayed-release capsules are indicated for the maintenance of healing of ee in adults. controlled studies do not extend beyond 6 months. adults esomeprazole magnesium delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of heartburn and other symptoms associated with gerd in adults. pediatric patients 12 years to 17 years of age esomeprazole magnesium delayed-release capsu

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

dr. reddy's laboratories inc. - 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) ].  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 was established in three clinical trials in adult patients with manic or mixed episode