নিউ জিলণ্ড - ইংরেজি - Medsafe (Medicines Safety Authority)

pharmacy retailing (nz) ltd t/a healthcare logistics - dextromethorphan hydrobromide monohydrate 10.5mg - pastille - 10.5 mg - active: dextromethorphan hydrobromide monohydrate 10.5mg excipient: acacia betadex citric acid limette flavour 18635/02 honey flavour 8366/001 levomenthol light liquid paraffin maltitol purified water quinoline yellow saccharin sodium sodium cyclamate white beeswax - bisolvon dry pastilles are used for the symptomatic treatment of dry, irritant, unproductive coughs.

অস্ট্রেলিয়া - ইংরেজি - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - rosuvastatin calcium, quantity: 10.42 mg - tablet, film coated - excipient ingredients: microcrystalline cellulose; crospovidone; lactose; magnesium stearate; light magnesium oxide; titanium dioxide; lactose monohydrate; hypromellose; triacetin; brilliant blue fcf aluminium lake; iron oxide red; quinoline yellow aluminium lake - pharmacor rosuvastatin should be used as an adjunct to diet when the response to diet and exercise is inadequate. ,prevention of cardiovascular events pharmacor rosuvastatin is indicated for prevention of major cardiovascular events in men ?50 years old and women ?60 years old with no clinically evident cardiovascular disease but with at least two conventional risk factors for cardiovascular disease (hypertension, low hdl-c, smoking, or a family history of premature coronary heart disease). pharmacor rosuvastatin is indicated to:,? reduce the risk of nonfatal myocardial infarction ? reduce the risk of nonfatal stroke ? reduce the risk of coronary artery revascularisation procedures.,in patients with hypercholesterolaemia pharmacor rosuvastatin is indicated for the treatment of hypercholesterolaemia (including familial hypercholesterolaemia). ,prior to initiating therapy with pharmacor rosuvastatin, secondary causes of hypercholesterolaemia (e.g. poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinaemias, obstructive liver disease, other drug therapy, alcoholism) should be identified and treated.

অস্ট্রেলিয়া - ইংরেজি - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - rosuvastatin calcium, quantity: 10.42 mg - tablet, film coated - excipient ingredients: crospovidone; lactose; microcrystalline cellulose; light magnesium oxide; magnesium stearate; titanium dioxide; lactose monohydrate; hypromellose; triacetin; brilliant blue fcf aluminium lake; iron oxide red; quinoline yellow aluminium lake - pharmacor rosuvastatin should be used as an adjunct to diet when the response to diet and exercise is inadequate. ,prevention of cardiovascular events pharmacor rosuvastatin is indicated for prevention of major cardiovascular events in men ?50 years old and women ?60 years old with no clinically evident cardiovascular disease but with at least two conventional risk factors for cardiovascular disease (hypertension, low hdl-c, smoking, or a family history of premature coronary heart disease). pharmacor rosuvastatin is indicated to:,? reduce the risk of nonfatal myocardial infarction ? reduce the risk of nonfatal stroke ? reduce the risk of coronary artery revascularisation procedures.,in patients with hypercholesterolaemia pharmacor rosuvastatin is indicated for the treatment of hypercholesterolaemia (including familial hypercholesterolaemia). ,prior to initiating therapy with pharmacor rosuvastatin, secondary causes of hypercholesterolaemia (e.g. poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinaemias, obstructive liver disease, other drug therapy, alcoholism) should be identified and treated.

মার্কিন যুক্তরাষ্ট্র - ইংরেজি - NLM (National Library of Medicine)

actavis pharma, inc. - temazepam (unii: chb1qd2qss) (temazepam - unii:chb1qd2qss) - temazepam 15 mg - temazepam capsules are indicated for the short-term treatment of insomnia (generally 7 to 10 days). for patients with short-term insomnia, instructions in the prescription should indicate that temazepam capsules should be used for short periods of time (7 to 10 days). the clinical trials performed in support of efficacy were 2 weeks in duration with the final formal assessment of sleep latency performed at the end of treatment. temazepam capsules are a schedule iv controlled substance. temazepam is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, diffic

মার্কিন যুক্তরাষ্ট্র - ইংরেজি - NLM (National Library of Medicine)

mckesson corporation dba sky packaging - lansoprazole (unii: 0k5c5t2qpg) (lansoprazole - unii:0k5c5t2qpg) - lansoprazole 30 mg - lansoprazole delayed-release capsules are indicated in adults for short-term treatment (for four weeks) for healing and symptom relief of active duodenal ulcer [see clinical studies ( 14.1) ].    triple therapy: lansoprazole delayed-release capsules/amoxicillin/clarithromycin lansoprazole delayed-release capsules in combination with amoxicillin plus clarithromycin as triple therapy is indicated in adults for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) to eradicate h. pylori. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies ( 14.2) ]. please refer to the full prescribing information for amoxicillin and clarithromycin. dual therapy: lansoprazole delayed-release capsules /amoxicillin lansoprazole delayed-release capsules in combination with amoxicillin as dual therapy is indicated in adults for the treatment of patients with h. pylori infection and duodenal ulcer disease (active or one year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected (see the clarithromycin prescribing information, microbiology section). eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence [see clinical studies ( 14.2) ]. please refer to the full prescribing information for amoxicillin. lansoprazole delayed-release capsules are indicated in adults to maintain healing of duodenal ulcers. controlled studies do not extend beyond 12 months. [see clinical studies ( 14.3) ]. lansoprazole delayed-release capsules are indicated in adults for short-term treatment (up to eight weeks) for healing and symptom relief of active benign gastric ulcer [see clinical studies ( 14.4) ]. lansoprazole delayed-release capsules are indicated in adults for the treatment of nsaid-associated gastric ulcer in patients who continue nsaid use. controlled studies did not extend beyond eight weeks [see clinical studies ( 14.5) ].   lansoprazole delayed-release capsules are indicated in adults for reducing the risk of nsaid-associated gastric ulcers in patients with a history of a documented gastric ulcer who require the use of an nsaid. controlled studies did not extend beyond 12 weeks [see clinical studies ( 14.6) ]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for the treatment of heartburn and other symptoms associated with gerd [see clinical studies ( 14.7) ]. lansoprazole delayed-release capsules are indicated for short-term treatment in adults and pediatric patients 12 to 17 years of age (up to eight weeks) and pediatric patients one to 11 years of age (up to 12 weeks) for healing and symptom relief of all grades of ee. for adults who do not heal with lansoprazole delayed-release capsules for eight weeks (5 to 10%), it may be helpful to give an additional eight weeks of treatment. if there is a recurrence of erosive esophagitis an additional eight week course of lansoprazole delayed-release capsules may be considered [see clinical studies ( 14.8)]. lansoprazole delayed-release capsules are indicated in adults to maintain healing of ee. controlled studies did not extend beyond 12 months [see clinical studies ( 14.9) ]. lansoprazole delayed-release capsules are indicated in adults for the long-term treatment of pathological hypersecretory conditions, including zollinger-ellison syndrome [see clinical studies ( 14.10) ]. - lansoprazole delayed-release capsules are contraindicated in patients with known severe hypersensitivity to any component of the formulation. 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 lansoprazole delayed-release capsules are contraindicated with rilpivirine-containing products [see drug interactions ( 7 )]. - for information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with lansoprazole delayed-release capsules, refer to the contraindications section of their prescribing information. risk summary available data from published observational studies overall do not indicate an association of adverse pregnancy outcomes with lansoprazole treatment (see data). in animal reproduction studies, oral administration of lansoprazole to rats during organogenesis through lactation at 6.4 times the maximum recommended human dose produced reductions in the offspring in femur weight, femur length, crown-rump length and growth plate thickness (males only) on postnatal day 21 (see data). these effects were associated with reduction in body weight gain. advise pregnant women of the potential risk to the fetus. the estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. if lansoprazole delayed-release capsules are administered with clarithromycin, the pregnancy information for clarithromycin also applies to the combination regimen. refer to the prescribing information for clarithromycin for more information on use in pregnancy. data human data available data from published observational studies failed to demonstrate an association of adverse pregnancy-related outcomes and lansoprazole 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 62 pregnant women administered median daily doses of 30 mg of lansoprazole were compared to a control group of 868 pregnant women who did not take any 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)=1.04, [95% confidence interval (ci) 0.25 to 4.21]. 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 lansoprazole in 794 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 odds ratio (or)=1.12, [95% ci 0.86 to 1.45] and for spontaneous abortions or=1.29, [95% ci 0.84 to 1.97]). animal data no adverse effects on embryo-fetal development occurred in studies performed in pregnant rats at oral lansoprazole doses up to 150 mg/kg/day (40 times the recommended human dose [30 mg/day] based on body surface area) administered during organogenesis and pregnant rabbits at oral lansoprazole doses up to 30 mg/kg/day (16 times the recommended human dose based on body surface area) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with lansoprazole at oral doses of 10 to 100 mg/kg/day (0.7 to 6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc [area under the plasma concentration-time curve]) administered during organogenesis through lactation. maternal effects observed at 100 mg/kg/day (6.4 times the maximum recommended human lansoprazole dose of 30 mg based on auc) included increased gestation period, decreased body weight gain during gestation, and decreased food consumption. the number of stillbirths was increased at this dose, which may have been secondary to maternal toxicity. body weight of pups was reduced at 100 mg/kg/day starting on postnatal day 11. femur weight, femur length, and crown-rump length were reduced at 100 mg/kg/day on postnatal day 21. femur weight was still decreased in the 100 mg/kg/day group at age 17 to 18 weeks. growth plate thickness was decreased in the 100 mg/kg/day males on postnatal day 21, and was increased in the 30 and 100 mg/kg/day males at age 17 to 18 weeks. the effects on bone parameters were associated with reduction in body weight gain. risk summary there is no information regarding the presence of lansoprazole in human milk, the effects on the breastfed infant, or the effects on milk production. however, lansoprazole and its metabolites are present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lansoprazole delayed-release capsules and any potential adverse effects on the breastfed child from lansoprazole delayed-release capsules or from the underlying maternal condition. the safety and effectiveness of lansoprazole delayed-release capsules have been established in pediatric patients one year to 17 years of age for short-term treatment of symptomatic gerd and erosive esophagitis. in clinical studies of symptomatic gerd and erosive esophagitis, lansoprazole was not administered beyond 12 weeks in patients one year to 11 years of age. it is not known if lansoprazole delayed-release capsules are safe and effective if used longer than the recommended duration. do not exceed the recommended dose and duration of use in pediatric patients (see juvenile animal toxicity data). lansoprazole was not effective in pediatric patients with symptomatic gerd one month to less than one year of age in a multicenter, double-blind, placebo controlled study. therefore, safety and effectiveness have not been established in patients less than one year. nonclinical studies in juvenile rats have demonstrated an adverse effect of heart valve thickening and bone changes at lansoprazole doses higher than the maximum recommended equivalent human dose. neonate to less than one year of age the pharmacokinetics of lansoprazole were studied in pediatric patients with gerd aged less than 28 days and one to 11 months. compared to healthy adults receiving 30 mg, neonates had higher exposure (mean weight-based normalized auc values 2.04 and 1.88 fold higher at doses of 0.5 mg/kg/day and 1 mg/kg/day, respectively). infants aged ≤10 weeks had clearance and exposure values that were similar to neonates. infants aged greater than 10 weeks who received 1 mg/kg/day had mean auc values that were similar to adults who received a 30 mg dose. lansoprazole was not found to be effective in a u.s. and polish four week multi-center, double-blind, placebo-controlled, parallel-group study of 162 patients between one month and less than 12 months of age with symptomatic gerd based on a medical history of crying/fussing/irritability associated with feedings who had not responded to conservative gerd management (i.e., non-pharmacologic intervention) for seven to 14 days. patients received lansoprazole as a suspension daily (0.2 to 0.3 mg/kg/day in infants ≤10 weeks of age or 1 to 1.5 mg/kg/day in infants greater than 10 weeks or placebo) for up to four weeks of double-blind treatment. the primary efficacy endpoint was assessed by greater than 50% reduction from baseline in either the percent of feedings with a crying/fussing/irritability episode or the duration (minutes) of a crying/fussing/irritability episode within one hour after feeding. there was no difference in the percentage of responders between the lansoprazole pediatric suspension group and placebo group (54% in both groups). there were no adverse events reported in pediatric clinical studies (one month to less than 12 months of age) that were not previously observed in adults. based on the results of the phase 3 efficacy study, lansoprazole was not shown to be effective. therefore, these results do not support the use of lansoprazole in treating symptomatic gerd in infants. one year to 11 years of age in an uncontrolled, open-label, u.s. multi-center study, 66 pediatric patients (one year to 11 years of age) with gerd were assigned, based on body weight, to receive an initial dose of either lansoprazole delayed-release capsules 15 mg daily if ≤ 30 kg or lansoprazole delayed-release capsules 30 mg daily if greater than 30 kg administered for eight to 12 weeks. the lansoprazole delayed-release capsules dose was increased (up to 30 mg twice daily) in 24 of 66 pediatric patients after two or more weeks of treatment if they remained symptomatic. at baseline, 85% of patients had mild to moderate overall gerd symptoms (assessed by investigator interview), 58% had non-erosive gerd and 42% had erosive esophagitis (assessed by endoscopy). after eight to 12 weeks of lansoprazole delayed-release capsules treatment, the intent-to-treat analysis demonstrated an approximate 50% reduction in frequency and severity of gerd symptoms. twenty one of 27 erosive esophagitis patients were healed at eight weeks and 100% of patients were healed at 12 weeks by endoscopy (table 4). final visit * % (n/n) * at week 8 or week 12 † symptoms assessed by patients diary kept by caregiver. ‡ no data were available for four pediatric patients. in a study of 66 pediatric patients in the age group one year to 11 years old after treatment with lansoprazole delayed-release capsules given orally in doses of 15 mg daily to 30 mg twice daily, increases in serum gastrin levels were similar to those observed in adult studies. median fasting serum gastrin levels increased 89% from 51 pg/ ml at baseline to 97 pg/ml [interquartile range (25 th to 75 th percentile) of 71 to 130 pg/ ml] at the final visit. the pediatric safety of lansoprazole delayed-release capsules has been assessed in 66 pediatric patients aged one to 11 years of age. of the 66 patients with gerd 85% (56/66) took lansoprazole delayed-release capsules for eight weeks and 15% (10/66) took it for 12 weeks. the most frequently reported (two or more patients) treatment-related adverse reactions in patients one to 11 years of age (n=66) were constipation (5%) and headache (3%). twelve years to 17 years of age in an uncontrolled, open-label, u.s. multi-center study, 87 adolescent patients (12 years to 17 years of age) with symptomatic gerd were treated with lansoprazole delayed-release capsules for eight to 12 weeks. baseline upper endoscopies classified these patients into two groups: 64 (74%) non-erosive gerd and 23 (26%) erosive esophagitis (ee). the non-erosive gerd patients received lansoprazole delayed-release capsules 15 mg daily for eight weeks and the ee patients received lansoprazole delayed-release capsules 30 mg daily for eight to 12 weeks. at baseline, 89% of these patients had mild to moderate overall gerd symptoms (assessed by investigator interviews). during eight weeks of lansoprazole delayed-release capsules treatment, adolescent patients experienced a 63% reduction in frequency and a 69% reduction in severity of gerd symptoms based on diary results. twenty one of 22 (95.5%) adolescent erosive esophagitis patients were healed after eight weeks of lansoprazole delayed-release capsules treatment. one patient remained unhealed after 12 weeks of treatment (table 5). *symptoms assessed by patient diary (parents/caregivers as necessary). † no data available for five patients. ‡ data from one healed patient was excluded from this analysis due to timing of final endoscopy. in these 87 adolescent patients, increases in serum gastrin levels were similar to those observed in adult studies, median fasting serum gastrin levels increased 42% from 45 pg/ml at baseline to 64 pg/ml [interquartile range (25 th to 75 th percentile) of 44 to 88 pg/ml] at the final visit. (normal serum gastrin levels are 25 to 111 pg/ml). the safety of lansoprazole delayed-release capsules has been assessed in these 87 adolescent patients. of the 87 adolescent patients with gerd, 6% (5/87) took lansoprazole delayed-release capsules for less than six weeks, 93% (81/87) for six to 10 weeks, and 1% (1/87) for greater than 10 weeks. the most frequently reported (at least 3%) treatment-related adverse reactions in these patients were headache (7%), abdominal pain (5%), nausea (3%) and dizziness (3%). treatment-related dizziness, reported in this prescribing information as occurring in less than 1% of adult patients, was reported in this study by three adolescent patients with non-erosive gerd, who had dizziness concurrently with other reactions (such as migraine, dyspnea, and vomiting). juvenile animal toxicity data heart valve thickening in two oral toxicity studies, thickening of the mitral heart valve occurred in juvenile rats treated with lansoprazole. heart valve thickening was observed primarily with oral dosing initiated on postnatal day 7 (age equivalent to neonatal humans) and postnatal day 14 (human age equivalent of approximately one year) at doses of 250 mg/kg/day and higher (at postnatal day 7 and postnatal day 14, respectively 6.2 times and 4.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). the treatment durations associated with heart valve thickening ranged from 5 days to 8 weeks. the findings reversed or trended towards reversibility after a 4-week drug-free recovery period. the incidence of heart valve thickening after initiation of dosing on postnatal day 21 (human age equivalent of approximately two years) was limited to a single rat (1/24) in groups given 500 mg/kg/day for 4 or 8 weeks (approximately 5.2 times the daily pediatric dose of 15 mg in pediatric patients age one to 11 years weighing 30 kg or less, based on auc). based on exposure margins, the risk of heart valve injury does not appear to be relevant to patients one year of age and older. bone changes in an eight-week oral toxicity study in juvenile rats with dosing initiated on postnatal day 7, doses equal to or greater than 100 mg/kg/day (2.5 times the daily pediatric dose of 15 mg in children age one to 11 years weighing 30 kg or less, based on auc) produced delayed growth, with impairment of weight gain observed as early as postnatal day 10 (age equivalent to neonatal humans). at the end of treatment, the signs of impaired growth at 100 mg/kg/day and higher included reductions in body weight (14 to 44% compared to controls), absolute weight of multiple organs, femur weight, femur length, and crown-rump length. femoral growth plate thickness was reduced only in males and only at the 500 mg/kg/day dose. the effects related to delayed growth persisted through the end of the four-week recovery period. longer term data were not collected. of the total number of patients (n=21,486) in clinical studies of lansoprazole delayed-release capusles, 16% of patients were aged 65 years and over, while 4% were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients and other reported clinical experience has not identified significant differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology ( 12.3) ]. in patients with various degrees of chronic hepatic impairment the exposure to lansoprazole was increased compared to healthy subjects with normal hepatic function [see clinical pharmacology ( 12.3) ]. no dosage adjustment for lansoprazole delayed-release capsules are necessary for patients with mild (child-pugh class a) or moderate (child-pugh class b) hepatic impairment. the recommended dosage is 15 mg orally daily in patients with severe hepatic impairment (child-pugh class c) [ see dosage and administration ( 2.3)] .

মার্কিন যুক্তরাষ্ট্র - ইংরেজি - NLM (National Library of Medicine)

amneal pharmaceuticals llc - divalproex sodium (unii: 644vl95ao6) (valproic acid - unii:614oi1z5wi) - valproic acid 250 mg - divalproex sodium extended-release tablets are a valproate and are indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. a manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. a mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode (depressed mood, loss of interest or pleasure in nearly all activities). the efficacy of divalproex sodium extended-release tablets is based in part on studies of divalproex sodium delayed-release tablets in this indication, and was confirmed in a 3-week trial with patients meeting dsm-iv tr criteria for bipolar i disorder, manic or mixed type, who were hospitalized for acute mania [see clinical studies (14.1)] . the effectiveness of valproate for long-term use in mania, i.e. more than 3 weeks, has not been demonstrated in controlled clinical trials. therefore, healthcare providers who elect to use divalproex sodium extended-release tablets for extended periods should continually reevaluate the long-term risk-benefits of the drug for the individual patient. divalproex sodium extended-release tablets are indicated as monotherapy and adjunctive therapy in the treatment of adult patients and pediatric patients down to the age of 10 years with complex partial seizures that occur either in isolation or in association with other types of seizures. divalproex sodium extended-release tablets are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures in adults and children 10 years of age or older, and adjunctively in adults and children 10 years of age or older with multiple seizure types that include absence seizures. simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. complex absence is the term used when other signs are also present. divalproex sodium extended-release tablets are indicated for prophylaxis of migraine headaches. there is no evidence that divalproex sodium extended-release tablets are useful in the acute treatment of migraine headaches. because of the risk to the fetus of decreased iq, neurodevelopmental disorders, neural tube defects, and other major congenital malformations, which may occur very early in pregnancy, valproate should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see warnings and precautions (5.2, 5.3, 5.4), use in specific populations (8.1)  and patient counseling information (17)] . for prophylaxis of migraine headaches, divalproex sodium extended-release tablets are contraindicated  in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)] . - divalproex sodium extended-release tablets should not be administered to patients with hepatic disease or significant hepatic dysfunction [see warnings and precautions (5.1)] . - divalproex sodium extended-release tablets are contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial dna polymerase γ (polg; e.g., alpers-huttenlocher syndrome) and children under two years of age who are suspected of having a polg-related disorder [see warnings and precautions (5.1)] . - divalproex sodium extended-release tablets are contraindicated in patients with known hypersensitivity to the drug [see warnings and precautions (5.12)] . - divalproex sodium extended-release tablets are contraindicated in patients with known urea cycle disorders [see warnings and precautions (5.6)] . - for use in prophylaxis of migraine headaches: divalproex sodium extended-release tablets are contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see warnings and precautions (5.2, 5.3, 5.4) and use in specific populations (8.1)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (aeds), including divalproex sodium extended-release, during pregnancy. encourage women who are taking divalproex sodium extended-release during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling toll-free 1-888-233-2334 or visiting the website, http://www.aedpregnancyregistry.org/. this must be done by the patient herself. risk summary for use in prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see contraindications (4)] . for use in epilepsy or bipolar disorder, valproate should not be used to treat women who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable [see boxed warning and warnings and precautions (5.2, 5.3)] . women with epilepsy who become pregnant while taking valproate should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects including spina bifida, but also malformations involving other body systems (e.g., craniofacial defects including oral clefts, cardiovascular malformations, hypospadias, limb malformations). this risk is dose-dependent; however, a threshold dose below which no risk exists cannot be established. in utero exposure to valproate may also result in hearing impairment or hearing loss. valproate polytherapy with other aeds has been associated with an increased frequency of congenital malformations compared with aed monotherapy. the risk of major structural abnormalities is greatest during the first trimester; however, other serious developmental effects can occur with valproate use throughout pregnancy. the rate of congenital malformations among babies born to epileptic mothers who used valproate during pregnancy has been shown to be about four times higher than the rate among babies born to epileptic mothers who used other anti-seizure monotherapies [see warnings and precautions (5.2) and data (human)] . epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores and a higher risk of neurodevelopmental disorders compared to children exposed to either another aed in utero or to no aeds in utero [see warnings and precautions (5.3) and data (human)] . an observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders [see data (human)] . in animal studies, valproate administration during pregnancy resulted in fetal structural malformations similar to those seen in humans and neurobehavioral deficits in the offspring at clinically relevant doses [see data (animal)] . there have been reports of hypoglycemia in neonates and fatal cases of hepatic failure in infants following maternal use of valproate during pregnancy. pregnant women taking valproate may develop hepatic failure or clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see warnings and precautions (5.1, 5.8)] . available prenatal diagnostic testing to detect neural tube and other defects should be offered to pregnant women using valproate. evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. it is not known whether the risk of neural tube defects or decreased iq in the offspring of women receiving valproate is reduced by folic acid supplementation. dietary folic acid supplementation both prior to conception and during pregnancy should be routinely recommended for patients using valproate [see warnings and precautions (5.2, 5.4)]. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk to prevent major seizures, women with epilepsy should not discontinue valproate abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. even minor seizures may pose some hazard to the developing embryo or fetus [see warnings and precautions (5.4)] . however, discontinuation of the drug may be considered prior to and during pregnancy in individual cases if the seizure disorder severity and frequency do not pose a serious threat to the patient. maternal adverse reactions pregnant women taking valproate may develop clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death [see warnings and precautions (5.8)] . if valproate is used in pregnancy, the clotting parameters should be monitored carefully in the mother. if abnormal in the mother, then these parameters should also be monitored in the neonate. patients taking valproate may develop hepatic failure [see boxed warning and warnings and precautions (5.1)] . fatal cases of hepatic failure in infants exposed to valproate in utero have also been reported following maternal use of valproate during pregnancy. hypoglycemia has been reported in neonates whose mothers have taken valproate during pregnancy. data human neural tube defects and other structural abnormalities there is an extensive body of evidence demonstrating that exposure to valproate in utero increases the risk of neural tube defects and other structural abnormalities. based on published data from the cdc’s national birth defects prevention network, the risk of spina bifida in the general population is about 0.06% to 0.07% (6 to 7 in 10,000 births) compared to the risk following in utero valproate exposure estimated to be approximately 1% to 2% (100 to 200 in 10,000 births). the naaed pregnancy registry has reported a major malformation rate of 9% to 11% in the offspring of women exposed to an average of 1,000 mg/day of valproate monotherapy during pregnancy. these data show an up to a five-fold increased risk for any major malformation following valproate exposure in utero compared to the risk following exposure in utero to other aeds taken as monotherapy. the major congenital malformations included cases of neural tube defects, cardiovascular malformations, craniofacial defects (e.g., oral clefts, craniosynostosis), hypospadias, limb malformations (e.g., clubfoot, polydactyly), and other malformations of varying severity involving other body systems [see warnings and precautions (5.2)] . effect on iq and neurodevelopmental effects published epidemiological studies have indicated that children exposed to valproate in utero have lower iq scores than children exposed to either another aed in utero or to no aeds in utero . the largest of these studies1 is a prospective cohort study conducted in the united states and united kingdom that found that children with prenatal exposure to valproate (n=62) had lower iq scores at age 6 (97 [95% c.i. 94 to 101]) than children with prenatal exposure to the other anti-epileptic drug monotherapy treatments evaluated: lamotrigine (108 [95% c.i. 105 to 110]), carbamazepine (105 [95% c.i. 102 to 108]) and phenytoin (108 [95% c.i. 104 to 112]). it is not known when during pregnancy cognitive effects in valproate-exposed children occur. because the women in this study were exposed to aeds throughout pregnancy, whether the risk for decreased iq was related to a particular time period during pregnancy could not be assessed [see warnings and precautions (5.3)] . although the available studies have methodological limitations, the weight of the evidence supports a causal association between valproate exposure in utero and subsequent adverse effects on neurodevelopment, including increases in autism spectrum disorders and attention deficit/hyperactivity disorder (adhd). an observational study has suggested that exposure to valproate products during pregnancy increases the risk of autism spectrum disorders. in this study, children born to mothers who had used valproate products during pregnancy had 2.9 times the risk (95% confidence interval [ci]: 1.7 to 4.9) of developing autism spectrum disorders compared to children born to mothers not exposed to valproate products during pregnancy. the absolute risks for autism spectrum disorders were 4.4% (95% ci: 2.6% to 7.5%) in valproate-exposed children and 1.5% (95% ci: 1.5% to 1.6%) in children not exposed to valproate products. another observational study found that children who were exposed to valproate in utero had an increased risk of adhd (adjusted hr 1.48; 95% ci, 1.09 to 2.00) compared with the unexposed children. because these studies were observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder and adhd cannot be considered definitive. other there are published case reports of fatal hepatic failure in offspring of women who used valproate during pregnancy. animal in developmental toxicity studies conducted in mice, rats, rabbits, and monkeys, increased rates of fetal structural abnormalities, intrauterine growth retardation, and embryo-fetal death occurred following administration of valproate to pregnant animals during organogenesis at clinically relevant doses (calculated on a body surface area [mg/m2 ] basis). valproate induced malformations of multiple organ systems, including skeletal, cardiac, and urogenital defects. in mice, in addition to other malformations, fetal neural tube defects have been reported following valproate administration during critical periods of organogenesis, and the teratogenic response correlated with peak maternal drug levels. behavioral abnormalities (including cognitive, locomotor, and social interaction deficits) and brain histopathological changes have also been reported in mice and rat offspring exposed prenatally to clinically relevant doses of valproate. risk summary   valproate is excreted in human milk. data in the published literature describe the presence of valproate in human milk (range: 0.4 mcg/ml to 3.9 mcg/ml), corresponding to 1% to 10% of maternal serum levels. valproate serum concentrations collected from breastfed infants aged 3 days postnatal to 12 weeks following delivery ranged from 0.7 mcg/ml to 4 mcg/ml, which were 1% to 6% of maternal serum valproate levels. a published study in children up to six years of age did not report adverse developmental or cognitive effects following exposure to valproate via breast milk [see data (human)] . there are no data to assess the effects of divalproex sodium delayed-release on milk production or excretion. clinical considerations the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for divalproex sodium delayed-release and any potential adverse effects on the breastfed infant from divalproex sodium delayed-release or from the underlying maternal condition. monitor the breastfed infant for signs of liver damage including jaundice and unusual bruising or bleeding. there have been reports of hepatic failure and clotting abnormalities in offspring of women who used valproate during pregnancy [see use in specific populations (8.1)] . data human in a published study, breast milk and maternal blood samples were obtained from 11 epilepsy patients taking valproate at doses ranging from 300 mg/day to 2,400 mg/day on postnatal days 3 to 6. in 4 patients who were taking valproate only, breast milk contained an average valproate concentration of 1.8 mcg/ml (range: 1.1 mcg/ml to 2.2 mcg/ml), which corresponded to 4.8% of the maternal plasma concentration (range: 2.7% to 7.4%). across all patients (7 of whom were taking other aeds concomitantly), similar results were obtained for breast milk concentration  (1.8 mcg/ml, range: 0.4 mcg/ml to 3.9 mcg/ml) and maternal plasma ratio (5.1%, range: 1.3% to 9.6%). a published study of 6 breastfeeding mother-infant pairs measured serum valproate levels during maternal treatment for bipolar disorder (750 mg/day or 1,000 mg/day). none of the mothers received valproate during pregnancy, and infants were aged from 4 weeks to 19 weeks at the time of evaluation. infant serum levels ranged from 0.7 mcg/ml to 1.5 mcg/ml. with maternal serum valproate levels near or within the therapeutic range, infant exposure was 0.9% to 2.3% of maternal levels. similarly, in 2 published case reports with maternal doses of 500 mg/day or 750 mg/day during breastfeeding of infants aged 3 months and 1 month, infant exposure was 1.5% and 6% that of the mother, respectively. a prospective observational multicenter study evaluated the long-term neurodevelopmental effects of aed use on children. pregnant women receiving monotherapy for epilepsy were enrolled with assessments of their children at ages 3 years and 6 years. mothers continued aed therapy during the breastfeeding period. adjusted iqs measured at 3 years for breastfed and non-breastfed children were 93 (n=11) and 90 (n=24), respectively. at 6 years, the scores for breastfed and non-breastfed children were 106 (n=11) and 94 (n=25), respectively (p=0.04). for other cognitive domains evaluated at 6 years, no adverse cognitive effects of continued exposure to an aed (including valproate) via breast milk were observed. contraception women of childbearing potential should use effective contraception while taking valproate [see boxed warning, warnings and precautions (5.4), drug interactions (7)  and use in specific populations (8.1)] . this is especially important when valproate use is considered for a condition not usually associated with permanent injury or death such as prophylaxis of migraine headaches [see contraindications (4)] . infertility there have been reports of male infertility coincident with valproate therapy [see adverse reactions (6.4)] . in animal studies, oral administration of valproate at clinically relevant doses resulted in adverse reproductive effects in males [see nonclinical toxicology (13.1)] . experience has indicated that pediatric patients under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions [see boxed warning  and warnings and precautions (5.1)] . when divalproex sodium extended-release 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 delayed-release was studied in seven pediatric clinical trials. two of the pediatric studies were double-blinded placebo-controlled trials to evaluate the efficacy of divalproex sodium extended-release for the indications of mania (150 patients aged 10 to 17 years, 76 of whom were on divalproex sodium extended-release) and migraine (304 patients aged 12 to 17 years, 231 of whom were on divalproex sodium extended-release). 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 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 for the indication of migraine (353 patients aged 12 to 17 years). one twelve-month study was conducted to evaluate the safety of divalproex sodium sprinkle capsules in the indication of partial seizures (169 patients aged 3 to 10 years). in these seven clinical trials, the safety and tolerability of divalproex sodium delayed-release in pediatric patients were shown to be comparable to those in adults [see adverse reactions (6)] . juvenile animal toxicology in studies of valproate in immature animals, toxic effects not observed in adult animals included retinal dysplasia in rats treated during the neonatal period (from postnatal day 4) and nephrotoxicity in rats treated during the neonatal and juvenile (from postnatal day 14) periods. the no-effect dose for these findings was less than the maximum recommended human dose on a mg/m2 basis. no patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. in a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. a higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. discontinuation of valproate was occasionally associated with the latter two events. it is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients. a study of elderly patients with dementia revealed drug related somnolence and discontinuation for somnolence [see warnings and precautions (5.14)] . the starting dose should be reduced in these patients, and dosage reductions or discontinuation should be considered in patients with excessive somnolence [see dosage and administration (2.5)] . there is insufficient information available to discern the safety and effectiveness of valproate for the prophylaxis of migraines in patients over 65. the capacity of elderly patients (age range: 68 to 89 years) to eliminate valproate has been shown to be reduced compared to younger adults (age range: 22 to 26 years) [see clinical pharmacology (12.3)] . liver disease liver disease impairs the capacity to eliminate valproate [see boxed warning, contraindications (4), warnings and precautions (5.1), and clinical pharmacology (12.3)] .

মার্কিন যুক্তরাষ্ট্র - ইংরেজি - NLM (National Library of Medicine)

northstar rx llc - zolpidem tartrate (unii: wy6w63843k) (zolpidem - unii:7k383oqi23) - zolpidem tartrate 5 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 to 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 - who have experienced complex sleep behaviors after taking zolpidem tartrate tablets [see warnings and precautions (5.1)]. -  with known hypersensitivity to zolpidem. observed reactions include anaphylaxis and angioedema [see warnings and precautions (5.4)] . risk summary neonates born to mothers using zolpidem late in the third trimester of pregnancy have been reported to experience symptoms of respiratory depression and sedation [see clinical   considerations and data] . published data on the use of zolpidem during pregnancy have not  reported a clear association with zolpidem and major birth defects [see data]. oral administration of zolpidem to pregnant rats and rabbits did not indicate a risk for adverse effects on fetal development at clinically relevant doses [see data]. the estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions zolpidem crosses the placenta and may produce respiratory depression and sedation in neonates. monitor neonates exposed to zolpidem tartrate during pregnancy and labor for signs of excess sedation, hypotonia, and respiratory depression and manage accordingly. data human data published data from observational studies, birth registries, and case reports on the use of zolpidem during pregnancy do not report a clear association with zolpidem and major birth defects.                  there are limited postmarketing reports of severe to moderate cases of respiratory depression that occurred after birth in neonates whose mothers had taken zolpidem during pregnancy. these cases required artificial ventilation or intratracheal intubation. the majority of neonates recovered within hours to a few weeks after birth once treated. zolpidem has been shown to cross the placenta. animal data oral administration of zolpidem to pregnant rats during the period of organogenesis at 4, 20, and 100 mg base/kg/day, which are approximately 5, 25, and 120 times the maximum recommended human dose (mrhd) of 10 mg/day (8 mg zolpidem base) based on mg/m2 body surface area, caused delayed fetal development (incomplete fetal skeletal ossification) at maternally toxic (ataxia) doses 25 and 120 times the mrhd based on mg/m2 body surface area. oral administration of zolpidem to pregnant rabbits during the period of organogenesis at 1, 4, and 16 mg base/kg/day, which are approximately 2.5, 10, and 40 times the mrhd of 10 mg/day (8 mg zolpidem base) based on mg/m2 body surface area caused embryo-fetal death and delayed fetal development (incomplete fetal skeletal ossification) at a maternally toxic (decreased body weight gain) dose 40 times the mrhd based on mg/m2 body surface area. oral administration of zolpidem to pregnant rats from day 15 of gestation through lactation at 4, 20, and 100 mg base/kg/day, which are approximately 5, 25, and 120 times the mrhd of 10 mg/day (8 mg zolpidem base) based on mg/m2 body surface area, delayed offspring growth and decreased survival at doses 25 and 120 times, respectively, the mrhd based on mg/m2 body surface area. risk summary limited data from published literature report the presence of zolpidem in human milk. there are reports of excess sedation in infants exposed to zolpidem through breastmilk [see clinical   considerations]. there is no information on the effects of zolpidem on milk production. the   developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for zolpidem tartrate and any potential adverse effects on the breastfed infant from zolpidem tartrate or from the underlying maternal condition. clinical considerations infants exposed to zolpidem tartrate through breastmilk should be monitored for excess sedation, hypotonia, and respiratory depression. a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 23 hours (approximately 5 elimination half-lives) after zolpidem tartrate administration in order to minimize drug exposure to a breast fed infant. zolpidem tartrate is not recommended for use in children. safety and effectiveness of zolpidem in pediatric patients below the age of 18 years have not been established. in an 8-week study in pediatric patients (aged 6 to 17 years) with insomnia associated with attention-deficit/hyperactivity disorder (adhd) an oral solution of zolpidem tartrate dosed at 0.25 mg/kg at bedtime did not decrease sleep latency compared to placebo. psychiatric and nervous system disorders comprised the most frequent (>5%) treatment emergent adverse reactions observed with zolpidem versus placebo and included dizziness (23.5% vs 1.5%), headache (12.5% vs 9.2%), and hallucinations were reported in 7% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations [see warnings and precautions (5.5)] . ten patients on zolpidem (7.4%) discontinued treatment due to an adverse reaction. a total of 154 patients in u.s. controlled clinical trials and 897 patients in non-u.s. clinical trials who received zolpidem were ≥60 years of age. for a pool of u.s. patients receiving zolpidem at doses of ≤10 mg or placebo, there were three adverse reactions occurring at an incidence of at least 3% for zolpidem and for which the zolpidem incidence was at least twice the placebo incidence (i.e., they could be considered drug related). a total of 30/1,959 (1.5%) non-u.s. patients receiving zolpidem reported falls, including 28/30 (93%) who were ≥70 years of age. of these 28 patients, 23 (82%) were receiving zolpidem doses >10 mg. a total of 24/1,959 (1.2%) non-u.s. patients receiving zolpidem reported confusion, including 18/24 (75%) who were ≥70 years of age. of these 18 patients, 14 (78%) were receiving zolpidem doses >10 mg. the dose of zolpidem tartrate in elderly patients is 5 mg to minimize adverse effects related to impaired motor and/or cognitive performance and unusual sensitivity to sedative/hypnotic drugs [see warnings and precautions (5.2)] . women clear zolpidem tartrate from the body at a lower rate than men. cmax and auc parameters of zolpidem were approximately 45% higher at the same dose in female subjects compared with male subjects. given the higher blood levels of zolpidem tartrate in women compared to men at a given dose, the recommended initial dose of zolpidem tartrate for adult women is 5 mg, and the recommended dose for adult men is 5 or 10 mg. in geriatric patients, clearance of zolpidem is similar in men and women. the recommended dose of zolpidem tartrate in geriatric patients is 5 mg regardless of gender. the recommended dose of zolpidem tartrate in patients with mild to moderate hepatic impairment is 5 mg once daily immediately before bedtime. avoid zolpidem tartrate use in patients with severe hepatic impairment as it may contribute to encephalopathy [see dosage and administration (2.2), warnings and precautions (5.8), clinical pharmacology (12.3)] . zolpidem tartrate is classified as a schedule iv controlled substance by federal regulation. abuse and addiction are separate and distinct from physical dependence and tolerance. abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug effects over time. tolerance may occur to both desired and undesired effects of drugs and may develop at different rates for different effects. addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. it is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. drug addiction is a treatable disease, using a multidisciplinary approach, but relapse is common. studies of abuse potential in former drug abusers found that the effects of single doses of zolpidem tartrate 40 mg were similar, but not identical, to diazepam 20 mg, while zolpidem tartrate 10 mg was difficult to distinguish from placebo. because persons with a history of addiction to, or abuse of, drugs or alcohol are at increased risk for misuse, abuse and addiction of zolpidem, they should be monitored carefully when receiving zolpidem or any other hypnotic. use of zolpidem tartrate may lead to the development of physical and/or psychological dependence. the risk of dependence increases with dose and duration of treatment. the risk of abuse and dependence is also greater in patients with a history of alcohol or drug abuse. zolpidem tartrate should be used with extreme caution in patients with current or past alcohol or drug abuse physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. these reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, convulsions, and delirium. the following adverse events, which are considered to meet the dsm-iii-r criteria for uncomplicated sedative/hypnotic withdrawal, were reported during clinical trials with zolpidem tartrate following placebo substitution occurring within 48 hours following last zolpidem treatment: fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic attack, nervousness, and abdominal discomfort. these reported adverse events occurred at an incidence of 1% or less. however, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. there have been postmarketing reports of abuse, dependence and withdrawal with zolpidem.

মার্কিন যুক্তরাষ্ট্র - ইংরেজি - NLM (National Library of Medicine)

northstar rx llc - alendronate sodium (unii: 2uy4m2u3ra) (alendronic acid - unii:x1j18r4w8p) - alendronic acid 10 mg - alendronate sodium tablets are indicated for the treatment of osteoporosis in postmenopausal women. in postmenopausal women, alendronate sodium tablets increase bone mass and reduce the incidence of fractures, including those of the hip and spine (vertebral compression fractures). [see clinical studies (14.1).] alendronate sodium tablets are indicated for the prevention of postmenopausal osteoporosis [see clinical studies (14.2)] . alendronate sodium tablets are indicated for treatment to increase bone mass in men with osteoporosis [see clinical studies (14.3)] . alendronate sodium tablets are indicated for the treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low bone mineral density [see clinical studies (14.4)] . alendronate sodium tablets are indicated for the treatment of paget’s disease of bone in men and women. treatment is indicated in patients with paget's disease of bone who have alkaline phosphatase at least two times the upper limit of normal, or those who are symptomatic, or those at risk for future complications from their disease. [see clinical studies (14.5).] the optimal duration of use has not been determined. the safety and effectiveness of alendronate sodium tablets for the treatment of osteoporosis are based on clinical data of four years duration. all patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. patients who discontinue therapy should have their risk for fracture re-evaluated periodically. alendronate sodium tablets are contraindicated in patients with the following conditions: - abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia [see warnings and precautions (5.1)] - inability to stand or sit upright for at least 30 minutes [see dosage and administration (2.6); warnings and precautions (5.1)] - hypocalcemia [see warnings and precautions (5.2)] - hypersensitivity to any component of this product. hypersensitivity reactions including urticaria and angioedema have been reported [see adverse reactions (6.2)] . risk summary   available data on the use of alendronate sodium in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. discontinue alendronate sodium when pregnancy is recognized. in animal reproduction studies, daily oral administration of alendronate to rats from before mating through the end of gestation or lactation showed decreased postimplantation survival and decreased pup body weight gain starting at doses equivalent to less than half of the highest recommended 40 mg clinical daily dose (based on body surface area, mg/m2 ). oral administration of alendronate to rats during organogenesis resulted in reduced fetal ossification starting at doses 3 times the 40 mg clinical daily dose. no similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at doses equivalent to approximately 10 times the 40 mg clinical daily dose. delayed or failed delivery of offspring, protracted parturition, and late pregnancy maternal and fetal deaths due to maternal hypocalcemia occurred in rats at oral doses as low as one tenth the 40 mg clinical daily dose (see data).   bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. the amount of bisphosphonate incorporated into adult bone and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. the impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defects, loss, or other adverse outcomes. in the u.s. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data   animal data reproduction studies in rats dosed orally from before mating to the end of gestation or lactation showed decreased postimplantation survival starting at 2 mg/kg/day and decreased body weight gain starting at 1 mg/kg/day, doses equivalent to less than half the 40 mg clinical daily dose based on body surface area, mg/m2 . incidence of incomplete fetal ossification in vertebral, skull, and sternebral bones were increased in rats dosed orally during organogenesis starting at 10 mg/kg/day (approximately 3 times the 40 mg clinical daily dose). no similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at up to 35 mg/kg/day (equivalent to approximately 10 times the 40 mg clinical daily dose). both total and ionized calcium decreased in pregnant rats dosed orally with 15 mg/kg/day alendronate (approximately 4 times the 40 mg clinical daily dose) resulting in delays and failures of delivery. protracted parturition due to maternal hypocalcemia was observed when rats were treated from before mating through gestation starting at 0.5 mg/kg/day (approximately one tenth the 40 mg clinical daily dose). maternotoxicity (late pregnancy deaths) also occurred in female rats treated orally with 15 mg/kg/day (approximately 4 times the 40 mg clinical daily dose) for varying gestational time periods. these maternal deaths were lessened but not eliminated by cessation of treatment. calcium supplementation in the drinking water or by subcutaneous minipump to rats dosed orally with 15 mg/kg/day alendronate could not ameliorate the hypocalcemia or prevent the dystocia-related maternal and neonatal deaths. however, intravenous calcium supplementation prevented maternal, but not neonatal deaths. risk summary   it is not known whether alendronate is present in human breast milk, affects human milk production, or has effects on the breastfed infant. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for alendronate sodium and any potential adverse effects on the breastfed child from alendronate sodium or from the underlying maternal condition. alendronate sodium is not indicated for use in pediatric patients. the safety and efficacy of alendronate sodium were examined in a randomized, double-blind, placebo-controlled two-year study of 139 pediatric patients, aged 4 to 18 years, with severe osteogenesis imperfecta (oi). one-hundred-and-nine patients were randomized to 5 mg alendronate daily (weight less than 40 kg) or 10 mg alendronate daily (weight greater than or equal to 40 kg) and 30 patients to placebo. the mean baseline lumbar spine bmd z-score of the patients was -4.5. the mean change in lumbar spine bmd z-score from baseline to month 24 was 1.3 in the alendronate sodium-treated patients and 0.1 in the placebo-treated patients. treatment with alendronate sodium did not reduce the risk of fracture. sixteen percent of the alendronate sodium patients who sustained a radiologically-confirmed fracture by month 12 of the study had delayed fracture healing (callus remodeling) or fracture non-union when assessed radiographically at month 24 compared with 9% of the placebo-treated patients. in alendronate sodium-treated patients, bone histomorphometry data obtained at month 24 demonstrated decreased bone turnover and delayed mineralization time; however, there were no mineralization defects. there were no statistically significant differences between the alendronate sodium and placebo groups in reduction of bone pain. the oral bioavailability in children was similar to that observed in adults. the overall safety profile of alendronate sodium in osteogenesis imperfecta  patients treated for up to 24 months was generally similar to that of adults with osteoporosis treated with alendronate sodium. however, there was an increased occurrence of vomiting in osteogenesis imperfecta patients treated with alendronate sodium compared to placebo. during the 24-month treatment period, vomiting was observed in 32 of 109 (29.4%) patients treated with alendronate sodium and 3 of 30 (10%) patients treated with placebo. in a pharmacokinetic study, 6 of 24 pediatric osteogenesis imperfecta patients who received a single oral dose of alendronate 35 or 70 mg developed fever, flu-like symptoms, and/or mild lymphocytopenia within 24 to 48 hours after administration. these events, lasting no more than 2 to 3 days and responding to acetaminophen, are consistent with an acute-phase response that has been reported in patients receiving bisphosphonates, including alendronate sodium. [see adverse reactions (6.2).] of the patients receiving alendronate sodium in the fracture intervention trial (fit), 71% (n=2302) were greater than  or equal to 65 years of age and 17% (n=550) were greater than or equal to 75 years of age. of the patients receiving alendronate sodium in the united states and multinational osteoporosis treatment studies in women, osteoporosis studies in men, glucocorticoid-induced osteoporosis studies, and paget’s disease studies [see clinical studies (14.1), (14.3), (14.4), (14.5)], 45%, 54%, 37%, and 70%, respectively, were 65 years of age or over. no overall differences in efficacy or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. alendronate sodium is not recommended for patients with creatinine clearance less than 35 ml/min. no dosage adjustment is necessary in patients with creatinine clearance values between 35 to 60 ml/min [see clinical pharmacology (12.3)] . as there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic impairment. no dosage adjustment is necessary [see clinical pharmacology (12.3)] .

মার্কিন যুক্তরাষ্ট্র - ইংরেজি - NLM (National Library of Medicine)

reliable 1 laboratories llc - calcium carbonate (unii: h0g9379fgk) (calcium cation - unii:2m83c4r6zb) - calcium carbonate 648 mg - antacid relieves - acid indigestion - heartburn - sour stomach - upset stomach associated with these symptoms stop use and ask a doctor if symptoms last more than 2 weeks.

মার্কিন যুক্তরাষ্ট্র - ইংরেজি - NLM (National Library of Medicine)

aurobindo pharma limited - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole 2 mg - aripiprazole tablets are indicated for the treatment of: - schizophrenia - irritability associated with autistic disorder - treatment of tourette’s disorder aripiprazole tablets are contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. reactions have ranged from pruritus/urticaria to anaphylaxis [see adverse reactions (6.2)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including aripiprazole, during pregnancy. healthcare providers are encouraged to register patients by contacting the national pregnancy registry for atypical antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/. risk summary neonates exposed to antipsychotic drugs, including aripiprazole, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see clinical considerations) . overall available data from published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data) . there are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including aripiprazole, during pregnancy (see clinical considerations). in animal reproduction studies, oral and intravenous aripiprazole administration during organogenesis in rats and/or rabbits at doses 10 and 19 times, respectively, the maximum recommended human dose (mrhd) of 30 mg/day based on mg/m2 body surface area, produced fetal death, decreased fetal weight, undescended testicles, delayed skeletal ossification, skeletal abnormalities, and diaphragmatic hernia. oral and intravenous aripiprazole administration during the pre- and post-natal period in rats at doses 10 times the mrhd based on mg/m2 body surface area, produced prolonged gestation, stillbirths, decreased pup weight, and decreased pup survival (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk there is a risk to the mother from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide. schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth. it is not known if this is a direct result of the illness or other comorbid factors.    fetal/neonatal adverse reactions extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs (including aripiprazole) during the third trimester of pregnancy. these symptoms have varied in severity. monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. data human data published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. a retrospective study from a medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. animal data in animal studies, aripiprazole demonstrated developmental toxicity, including possible teratogenic effects in rats and rabbits. in pregnant rats treated orally with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are approximately 1, 3 and 10 times the mrhd of 30 mg/day based on mg/m2 body surface area, a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight and undescended testes, were observed at 10 times the mrhd. delayed skeletal ossification was observed at 3 and 10 times the mrhd. delivered offspring had increased incidences of hepatodiaphragmatic nodules and diaphragmatic hernia were observed at 10 times the mrhd (the other dose groups were not examined for these findings). postnatally, delayed vaginal opening was seen at 3 and 10 times the mrhd. impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased post-implantation loss, likely mediated through effects on female offspring) were observed at 10 times the mrhd; however, there was no evidence to suggest that these developmental effects were secondary to maternal toxicity. in pregnant rabbits treated orally with aripiprazole during organogenesis at doses of 10, 30, and 100 mg/kg/day which are 6, 19, and 65 times the mrhd of 30 mg/day based on mg/m2 body surface area, decreased maternal food consumption, and increased abortions as well as increased fetal mortality were observed at 65 times the mrhd. decreased fetal weight and increased incidence of fused sternebrae were observed at 19 and 65 times the mrhd. in rats treated orally with aripiprazole peri- and postnatally from gestation day 17 through postpartum day 21 at doses of 3, 10, and 30 mg/kg/day which are 1, 3, and 10 times the mrhd of 30 mg/day based on mg/m2 body surface area slight maternal toxicity and slightly prolonged gestation were observed at 10 times the mrhd. an increase in stillbirths and, decreases in pup weight (persisting into adulthood) and survival were also seen at this dose. risk summary limited data from published literature report the presence of aripiprazole in human breast milk, at relative infant doses ranging between 0.7% to 8.3% of the maternal weight-adjusted dosage. there are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole. the development and health benefits of breastfeeding should be considered along with the mother’s clinical need for aripiprazole and any potential adverse effects on the breastfed infant from aripiprazole or from the underlying maternal condition. the pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients, 10 to 17 years of age, were similar to those in adults after correcting for the differences in body weight [see clinical pharmacology (12.3)]. schizophrenia safety and effectiveness in pediatric patients with schizophrenia were established in a 6 week, placebo-controlled clinical trial in 202 pediatric patients aged 13 to 17 years [see dosage and administration (2.1), adverse reactions (6.1), and clinical studies (14.1)]. although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.   irritability associated with autistic disorder safety and effectiveness in pediatric patients demonstrating irritability associated with autistic disorder were established in two 8 week, placebo-controlled clinical trials in 212 pediatric patients aged 6 to 17 years [see indications and usage (1), dosage and administration (2.4), adverse reactions (6.1), and clinical studies (14.4)] . a maintenance trial was conducted in pediatric patients (6 to 17 years of age) with irritability associated with autistic disorder. the first phase of this trial was an open-label, flexibly dosed (aripiprazole 2 to 15 mg/day) phase in which patients were stabilized (defined as >25% improvement on the abc-i subscale, and a cgi-i rating of “much improved” or “very much improved”) on aripiprazole for 12 consecutive weeks. overall, 85 patients were stabilized and entered the second, 16 week, double-blind phase where they were randomized to either continue aripiprazole treatment or switch to placebo. in this trial, the efficacy of aripiprazole for the maintenance treatment of irritability associated with autistic disorder was not established. tourette’s disorder safety and effectiveness of aripiprazole in pediatric patients with tourette’s disorder were established in one 8 week (aged 7 to 17 years) and one 10 week trial (aged 6 to 18 years) in 194 pediatric patients [see dosage and administration (2.5), adverse reactions (6.1), and clinical studies (14.5)] . maintenance efficacy in pediatric patients has not been systematically evaluated. juvenile animal studies aripiprazole in juvenile rats caused mortality, cns clinical signs, impaired memory and learning,  and  delayed  sexual  maturation when  administered at  oral  doses  of  10,  20, 40 mg/kg/day  from  weaning  (21  days  old)  through  maturity  (80  days   old).  at 40 mg/kg/day, mortality, decreased activity, splayed hind limbs, hunched posture, ataxia, tremors and other cns signs were observed in both genders. in addition, delayed sexual maturation was observed in males. at all doses and in a dose-dependent manner, impaired memory and learning, increased motor activity, and histopathology changes in the pituitary (atrophy), adrenals (adrenocortical hypertrophy), mammary glands (hyperplasia and increased secretion), and female reproductive organs (vaginal mucification, endometrial atrophy, decrease in ovarian corpora lutea) were observed. the changes in female reproductive organs were considered secondary to the increase in prolactin serum levels. a no observed adverse effect level (noael) could not be determined and, at the lowest tested dose of 10 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2 month recovery period, and most of the drug effects in juvenile rats were also observed in adult rats from previously conducted studies. aripiprazole in juvenile dogs (2 months old) caused cns clinical signs of tremors, hypoactivity, ataxia, recumbency and limited use of hind limbs when administered orally for 6 months at 3, 10, 30 mg/kg/day. mean body weight and weight gain were decreased up to 18% in females in all drug groups relative to control values. a noael could not be determined and, at the lowest tested dose of 3 mg/kg/day, there is no safety margin relative to the systemic exposures (auc0-24 ) for aripiprazole or its major active metabolite in adolescents at the maximum recommended pediatric dose of 15 mg/day. all drug-related effects were reversible after a 2 month recovery period. no dosage adjustment is recommended for elderly patients [see boxed warning, warnings and precautions (5.1), and clinical pharmacology (12.3)]. of the 13,543 patients treated with oral aripiprazole in clinical trials, 1,073 (8%) were ≥65 years old and 799 (6%) were ≥75 years old. placebo-controlled studies of oral aripiprazole in schizophrenia, or other indications did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. aripiprazole is not approved for the treatment of patients with psychosis associated with alzheimer’s disease [see boxed warning and warnings and precautions (5.1)]. dosage adjustment is recommended in known cyp2d6 poor metabolizers due to high aripiprazole concentrations. approximately 8% of caucasians and 3 to 8% of black/african americans cannot metabolize cyp2d6 substrates and are classified as poor metabolizers (pm) [see dosage and administration (2.7) and clinical pharmacology (12.3)]. no  dosage  adjustment for  aripiprazole  is  required  on  the  basis  of  a  patient’s  hepatic function (mild to severe hepatic impairment, child-pugh score between 5 and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between 15 and 90 ml/minute) [see clinical pharmacology (12.3)]. no dosage adjustment for aripiprazole is required on the basis of a patient’s sex, race, or smoking status [see clinical pharmacology (12.3)]. aripiprazole is not a controlled substance. aripiprazole has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of aripiprazole misuse or abuse (e.g., development of tolerance, increases in dose, drug-seeking behavior). in physical dependence studies in monkeys, withdrawal symptoms were observed upon abrupt cessation of dosing. while the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed.