Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - prochlorperazine maleate (unii: i1t8o1jtl6) (prochlorperazine - unii:yhp6ylt61t) - for control of severe nausea and vomiting. for the treatment of schizophrenia. prochlorperazine is effective for the short-term treatment of generalized non-psychotic anxiety. however, prochlorperazine is not the first drug to be used in therapy for most patients with non-psychotic anxiety, because certain risks associated with its use are not shared by common alternative treatments (e.g., benzodiazepines). when used in the treatment of non-psychotic anxiety, prochlorperazine should not be administered at doses of more than 20 mg per day or for longer than 12 weeks, because the use of prochlorperazine at higher doses or for longer intervals may cause persistent tardive dyskinesia that may prove irreversible (see warnings ). the effectiveness of prochlorperazine as treatment for non-psychotic anxiety was established in 4-week clinical studies of outpatients with generalized anxiety disorder. this evidence does not predict that prochlorperazinewill be useful in patients with other non-psychotic conditions in wh

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - nizatidine (unii: p41pml4ghr) (nizatidine - unii:p41pml4ghr) - nizatidine 150 mg - nizatidine capsules usp are indicated for up to 8 weeks for the treatment of active duodenal ulcer. in most patients, the ulcer will heal within 4 weeks. nizatidine capsules usp are indicated for maintenance therapy for duodenal ulcer patients at a reduced dosage of 150 mg h.s. after healing of an active duodenal ulcer. the consequences of continuous therapy with nizatidine for longer than 1 year are not known. nizatidine capsules usp are indicated for up to 12 weeks for the treatment of endoscopically diagnosed esophagitis, including erosive and ulcerative esophagitis, and associated heartburn due to gerd. nizatidine capsules usp are indicated for up to 8 weeks for the treatment of active benign gastric ulcer. before initiating therapy, care should be taken to exclude the possibility of malignant gastric ulceration.

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - fenofibrate (unii: u202363uos) (fenofibric acid - unii:bgf9mn2hu1) - fenofibrate 67 mg - fenofibrate capsules are indicated as adjunctive therapy to diet for the reduction of ldl-c, total-c, triglycerides and apo b in adult patients with primary hypercholesterolemia or mixed dyslipidemia (fredrickson types iia and iib). lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol when response to diet and non-pharmacological interventions alone has been inadequate (see national cholesterol education program [ncep] treatment guidelines, below). fenofibrate capsules are also indicated as adjunctive therapy to diet for treatment of adult patients with hypertriglyceridemia (fredrickson types iv and v hyperlipidemia). improving glycemic control in diabetic patients showing fasting chylomicronemia will usually reduce fasting triglycerides and eliminate chylomicronemia thereby obviating the need for pharmacologic intervention. markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dl) may increase the risk of developing pancreatitis. the effect of fenofibrate therapy on reducing this risk has not been adequately studied. drug therapy is not indicated for patients with type i hyperlipoproteinemia, who have elevations of chylomicrons and plasma triglycerides, but who have normal levels of very low density lipoprotein (vldl). inspection of plasma refrigerated for 14 hours is helpful in distinguishing types i, iv and v hyperlipoproteinemia2 . the initial treatment for dyslipidemia is dietary therapy specific for the type of lipoprotein abnormality. excess body weight and excess alcoholic intake may be important factors in hypertriglyceridemia and should be addressed prior to any drug therapy. physical exercise can be an important ancillary measure. diseases contributory to hyperlipidemia, such as hypothyroidism or diabetes mellitus should be looked for and adequately treated. estrogen therapy, like thiazide diuretics and beta-blockers, is sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia. in such cases, discontinuation of the specific etiologic agent may obviate the need for specific drug therapy of hypertriglyceridemia. the use of drugs should be considered only when reasonable attempts have been made to obtain satisfactory results with non-drug methods. if the decision is made to use drugs, the patient should be instructed that this does not reduce the importance of adhering to diet (see error! hyperlink reference not valid. and error! hyperlink reference not valid. ). fredrickson classification of hyperlipoproteinemias lipid elevation type lipoprotein elevated major minor i (rare) chylomicrons tg ↑↔c iia ldl c - iib ldl, vldl c tg iii (rare) idl c, tg - iv vldl tg ↑↔c v (rare) chylomicrons, vldl tg ↑↔ ldl-cholesterol mg/dl (mmol/l) definite atherosclerotic disease1 two or more other risk factors2 initiation level goal no no ≥ 190 (≥ 4.9) < 160 (< 4.1) no yes ≥ 160 (≥ 4.1) < 130 (< 3.4) yes yes or no ≥ 1303 (≥ 3.4) < 100 (< 2.6) 1 coronary heart disease or peripheral vascular disease (including symptomatic carotid artery disease). 2 other risk factors for coronary heart disease (chd) include: age (males: ≥ 45 years; females: ≥ 55 years or premature menopause without estrogen replacement therapy); family history of premature chd; current cigarette smoking; hypertension; confirmed hdl-c < 35 mg/dl (< 0.91 mmol/l); and diabetes mellitus. subtract 1 risk factor if hdl-c is ≥ 60 mg/dl (≥ 1.6 mmol/l). 3 in chd patients with ldl-c levels 100 to 129 mg/dl, the physician should exercise clinical judgment in deciding whether to initiate drug treatment. fenofibrate capsules are contraindicated in patients who exhibit hypersensitivity to fenofibrate. fenofibrate capsules are contraindicated in patients with hepatic or severe renal dysfunction, including primary biliary cirrhosis, and patients with unexplained persistent liver function abnormality. fenofibrate capsules are contraindicated in patients with preexisting gallbladder disease (see warnings ).

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glenmark pharmaceuticals inc., usa - propafenone hydrochloride (unii: 33xch0hocd) (propafenone - unii:68iqx3t69u) - propafenone hydrochloride 225 mg - propafenone hydrochloride extended-release capsules are indicated to prolong the time to recurrence of symptomatic atrial fibrillation (af) in patients with episodic (most likely paroxysmal or persistent) af who do not have structural heart disease. usage considerations: propafenone hydrochloride extended-release capsules are contraindicated in the following circumstances: risk summary in the absence of studies in pregnant women, available data from published case reports and several decades of postmarketing experience with use of propafenone hydrochloride extended-release capsules in pregnancy have not identified any drug-associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. untreated arrhythmias during pregnancy may pose a risk to the pregnant woman and fetus (see clinical considerations). propafenone and its metabolite, 5-oh-propafenone, cross the placenta in humans. in animal studies, propafenone was not teratogenic. at maternally toxic doses (ranging from 2 to 6 times the maximum recommended human dose [mrhd]), there was evidence of adverse developmental outcomes when administered to pregnant rabbits and rats during organogenesis or when administered to pregnant rats during mid-gestation through weaning of their offspring (see data) . the estimated background risks 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 disease-associated maternal and/or embryo/fetal risk: the incidence of vt is increased and may be more symptomatic during pregnancy. ventricular arrhythmias most often occur in pregnant women with underlying cardiomyopathy, congenital heart disease, valvular heart disease, or mitral valve prolapse. breakthrough arrhythmias may also occur during pregnancy, as therapeutic treatment levels may be difficult to maintain due to the increased volume of distribution and increased drug metabolism inherent in the pregnant state. fetal/neonatal adverse reactions: propafenone and its metabolite have been shown to cross the placenta. adverse reactions such as fetal/neonatal arrhythmias have been associated with the use of other antiarrhythmic agents by pregnant women. fetal/neonatal monitoring for signs and symptoms of arrhythmia is recommended during and after treatment of pregnant women with propafenone. labor or delivery: risk of arrhythmias may increase during labor and delivery. patients treated with propafenone hydrochloride extended-release capsules should be monitored continuously for arrhythmias during labor and delivery [see warnings and precautions (5.1)] . data propafenone has been shown to cause embryo-fetal mortality in rabbits and rats when given orally during organogenesis at maternally toxic doses of 150 mg/kg/day (rabbit: maternal mortality, decreased body weight gain and food consumption at approximately 3 times the mrhd on a mg/m2 basis) and 600 mg/kg/day (rat: maternal decreased body weight gain and food consumption at approximately 6 times the mrhd on a mg/m2 basis). in addition, a maternally toxic dose of 600 mg/kg/day (approximately 6 times the mrhd on a mg/m2 basis) also caused decreased fetal weights in rats. increased placental weights and delayed ossification occurred in rabbits at a dose of 30 mg/kg/day (less than the mrhd on a mg/m2 basis) in the absence of maternal toxicity. no adverse developmental outcomes in the absence of maternal toxicity were seen following oral doses of 15 mg/kg/day to rabbits or up to 270 mg/kg/day to rats administered during organogenesis (equivalent to 0.3 times or approximately 3 times the mrhd on a mg/m2 basis, respectively). in an oral study, female rats received propafenone up to 500 mg/kg/day from mid-gestation through weaning. at 90 mg/kg/day (equivalent to the mrhd on a mg/m2 basis), there were no adverse developmental outcomes in the absence of maternal toxicity. however, doses ≥180 mg/kg/day (2 or more times the mrhd on a mg/m2 basis) produced increases in maternal deaths and resulted in reductions in neonatal survival, body weight gain, and delayed development in the presence of maternal toxicity. risk summary propafenone and its active metabolite, 5-oh-propafenone, are present in human milk, but the levels are likely to be low. there are no data on the effects of propafenone on the breastfed infant or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for propafenone and any potential adverse effects on the breastfed infant from propafenone or from the underlying maternal condition. infertility males: based on human and animal studies, propafenone hydrochloride extended-release capsules may transiently impair spermatogenesis in males. evaluation of the effects on spermatogenesis was performed in 11 healthy males given oral propafenone 300 mg b.i.d. for 4 days, which was then increased to 300 mg t.i.d. for an additional 4 days. study findings included a 28% reduction in semen sample volume on treatment day 8 and a 27% reduction in sperm count 64 days after treatment (both values remained within the laboratories normal reference range). these effects were not seen in follow-up visits up to 120 days after treatment. reversible decreases in spermatogenesis have been demonstrated in monkeys, dogs, and rabbits after lethal or near-lethal intravenous doses of propafenone [see nonclinical toxicology (13.1 )]. the safety and effectiveness of propafenone in pediatric patients have not been established. of the total number of subjects in phase 3 clinical trials of propafenone hydrochloride extended-release 46% were 65 and older, while 16% were 75 and older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals at higher doses cannot be ruled out. the effect of age on the pharmacokinetics and pharmacodynamics of propafenone has not been studied.

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - naproxen (unii: 57y76r9atq) (naproxen - unii:57y76r9atq) - naproxen 250 mg - naproxen tablets and naproxen sodium tablets are indicated for: the relief of the signs and symptoms of: naproxen tablets and naproxen sodium tablets are also indicated for: the relief of signs and symptoms of: the management of: naproxen tablets and naproxen sodium tablets are contraindicated in the following patients: risk summary use of nsaids, including naproxen tablets and naproxen sodium tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. because of these risks, limit dose and duration of naproxen tablets or naproxen sodium tablets use between about 20 and 30 weeks of gestation, and avoid naproxen tablets and naproxen sodium tablets use at about 30 weeks of gestation and later in pregnancy (see clinical considerations, data). premature closure of fetal ductus arteriosus use of nsaids, including naproxen tablets and naproxen sodium tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding other potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies in rats, rabbits, and mice no evidence of teratogenicity or fetal harm when naproxen was administered during the period of organogenesis at doses 0.13, 0.26, and 0.6 times the maximum recommended human daily dose of 1500 mg/day, respectively [see data ]. based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. in animal studies, administration of prostaglandin synthesis inhibitors such as naproxen, resulted in increased pre-and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. 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 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 premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including naproxen tablets and naproxen sodium tablets, can cause premature closure of the fetal ductus arteriosus (see data ). oligohydramnios/neonatal renal impairment: if an nsaid is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. if naproxen tablets or naproxen sodium tablets treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue naproxen tablets and naproxen sodium tablets, and follow up according to clinical practice (see data ). labor or delivery there are no studies on the effects of naproxen tablets or naproxen sodium tablets during labor or delivery. in animal studies, nsaids, including naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data there is some evidence to suggest that when inhibitors of prostaglandin synthesis are used to delay preterm labor, there is an increased risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus, and intracranial hemorrhage. naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction, and abnormal prostaglandin e levels in preterm infants. because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly starting at 30-weeks of gestation, or third trimester) should be avoided. premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data reproduction studies have been performed in rats at 20 mg/kg/day (0.13 times the maximum recommended human daily dose of 1500 mg/day based on body surface area comparison), rabbits at 20 mg/kg/day (0.26 times the maximum recommended human daily dose, based on body surface area comparison), and mice at 170 mg/kg/day (0.6 times the maximum recommended human daily dose based on body surface area comparison) with no evidence of impaired fertility or harm to the fetus due to the drug. risk summary the naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for naproxen tablets or naproxen sodium tablets and any potential adverse effects on the breastfed infant from the naproxen tablets or naproxen sodium tablets or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including naproxen tablets and naproxen sodium tablets, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. small studies in women treated with nsaids have also shown a reversible delay in ovulation. consider withdrawal of nsaids, including naproxen tablets and naproxen sodium tablets, in women who have difficulties conceiving or who are undergoing investigation of infertility. safety and effectiveness in pediatric patients below the age of 2 years have not been established. pediatric dosing recommendations for polyarticular juvenile idiopathic arthritis are based on well-controlled studies [see dosage and administration (2) ]. there are no adequate effectiveness or dose-response data for other pediatric conditions, but the experience in polyarticular juvenile idiopathic arthritis and other use experience have established that single doses of 2.5 to 5 mg/kg as naproxen suspension, with total daily dose not exceeding 15 mg/kg/day, are well tolerated in pediatric patients over 2 years of age. the hepatic and renal tolerability of long-term naproxen administration was studied in two double-blind clinical trials involving 586 patients. of the patients studied, 98 patients were age 65 and older and 10 of the 98 patients were age 75 and older. naproxen was administered at doses of 375 mg twice daily or 750 mg twice daily for up to 6 months. transient abnormalities of laboratory tests assessing hepatic and renal function were noted in some patients, although there were no differences noted in the occurrence of abnormal values among different age groups. elderly patients, compared to younger patients, are at greater risk for nsaid-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. if the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects [see warnings and precautions (5.1, 5.2, 5.3, 5.6, 5.14) ]. studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. the clinical significance of this finding is unclear, although it is possible that the increase in free naproxen concentration could be associated with an increase in the rate of adverse events per a given dosage in some elderly patients. caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. as with other drugs used in the elderly, it is prudent to use the lowest effective dose. experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nonsteroidal anti- inflammatory drugs. elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. most spontaneous reports of fatal gi events are in the geriatric population [see warnings and precautions (5.2) ]. naproxen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see clinical pharmacology ( error! hyperlink reference not valid. ) ]. geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nonsteroidal anti-inflammatory drugs [see warnings and precautions (5.6) ]. caution is advised when high doses are required and some adjustment of dosage may be required in these patients. it is prudent to use the lowest effective dose [see clinical pharmacology ( error! hyperlink reference not valid. ) ]. naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 ml/min) [see warnings and precautions (5.6), clinical pharmacology ( error! hyperlink reference not valid. ) ].

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - aprepitant (unii: 1nf15yr6uy) (aprepitant - unii:1nf15yr6uy) - aprepitant 40 mg - aprepitant capsules, in combination with other antiemetic agents, are indicated in patients 12 years of age and older for the prevention of: aprepitant capsules are indicated in adults for the prevention of postoperative nausea and vomiting. aprepitant is contraindicated in patients: risk summary there are insufficient data on use of aprepitant in pregnant women to inform a drug associated risk. in animal reproduction studies, no adverse developmental effects were observed in rats or rabbits exposed during the period of organogenesis to systemic drug levels (auc) approximately 1.5 times the adult human exposure at the 125 mg/80 mg/80 mg aprepitant regimen [see data] . the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. 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. data animal data in embryofetal development studies in rats and rabbits, aprepitant was administered during the period of organogenesis at oral doses up to 1000 mg/kg twice daily in rats and up to the maximum tolerated dose of 25 mg/kg/day in rabbits. no embryofetal lethality or malformations were observed at any dose level in either species. the exposures (auc) in pregnant rats at 1000 mg/kg twice daily and in pregnant rabbits at 125 mg/kg/day were approximately 1.5 times the adult exposure at the 125 mg/80 mg/80 mg aprepitant regimen. aprepitant crosses the placenta in rats and rabbits. risk summary lactation studies have not been conducted to assess the presence of aprepitant in human milk, the effects on the breastfed infant, or the effects on milk production. aprepitant is present in rat milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for aprepitant and any potential adverse effects on the breastfed infant from aprepitant or from the underlying maternal condition. contraception upon administration of aprepitant, the efficacy of hormonal contraceptives may be reduced. advise females of reproductive potential using hormonal contraceptives to use an effective alternative or back-up non-hormonal contraceptive (such as condoms and spermicides) during treatment with aprepitant and for 1 month following the last dose [see drug interactions (7.1), clinical pharmacology (12.3)] .  prevention of nausea and vomiting associated with hec or mec the safety and effectiveness of aprepitant capsules in pediatric patients 12 years of age and older for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of hec, including high-dose cisplatin, and mec. use of aprepitant in these age groups is supported by evidence from 95 pediatric patients in a randomized, double-blind, active comparator controlled clinical study (n = 95 patients aged 12 through 17 years). aprepitant was studied in combination with ondansetron with or without dexamethasone (at the discretion of the physician) [see clinical studies (14.3)] . adverse reactions were similar to those reported in adult patients [see adverse reactions (6.1)] . the safety and effectiveness of aprepitant for the prevention of nausea and vomiting associated with hec or mec have not been established in patients less than 6 months. prevention of postoperative nausea and vomiting (ponv) the safety and effectiveness of aprepitant have not been established for the prevention of postoperative nausea and vomiting in pediatric patients. juvenile animal study a study was conducted in young rats to evaluate the effects of aprepitant on growth and on neurobehavioral and sexual development. rats were treated at oral doses up to the maximum feasible dose of 1000 mg/kg twice daily (providing exposure in male rats lower than the exposure at the recommended pediatric human dose and exposure in female rats equivalent to the pediatric human exposure) from the early postnatal period (postnatal day 10) through postnatal day 58. slight changes in the onset of sexual maturation were observed in female and male rats; however, there were no effects on mating, fertility, embryonic-fetal survival, or histomorphology of the reproductive organs. there were no effects in neurobehavioral tests of sensory function, motor function, and learning and memory. of the 544 adult cancer patients treated with aprepitant in cinv clinical studies, 31% were aged 65 and over, while 5% were aged 75 and over. of the 1120 adult cancer patients treated with aprepitant in ponv clinical studies, 7% were aged 65 and over, while 2% were aged 75 and over. other reported clinical experience with aprepitant has not identified differences in responses between elderly and younger patients. in general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy [see clinical pharmacology (12.3)] .  the pharmacokinetics of aprepitant in patients with severe renal impairment and those with end stage renal disease (esrd) requiring hemodialysis were similar to those of healthy subjects with normal renal function. no dosage adjustment is necessary for patients with any degree of renal impairment or for patients with esrd undergoing hemodialysis. the pharmacokinetics of aprepitant in patients with mild and moderate hepatic impairment were similar to those of healthy subjects with normal hepatic function. no dosage adjustment is necessary for patients with mild to moderate hepatic impairment (child-pugh score 5 to 9). there are no clinical or pharmacokinetic data in patients with severe hepatic impairment (child-pugh score greater than 9). therefore, additional monitoring for adverse reactions in these patients may be warranted when aprepitant is administered [see clinical pharmacology (12.3)] .

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glenmark pharmaceuticals inc., usa - aspirin (unii: r16co5y76e) (aspirin - unii:r16co5y76e), dipyridamole (unii: 64alc7f90c) (dipyridamole - unii:64alc7f90c) - aspirin and extended-release dipyridamole capsules are indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis. aspirin and extended-release dipyridamole capsules are contraindicated in patients with known hypersensitivity to any of the product components. aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug (nsaid) products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. aspirin may cause severe urticaria, angioedema or bronchospasm. do not use aspirin in children or teenagers with viral infections because of the risk of reye syndrome. risk summary available data from published studies and postmarketing experience with aspirin and extended-release dipyridamole capsules use during pregnancy have not identified a clear association between aspirin and extended-release dipyridamole capsules use and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see data) . aspirin and extended-release dipyridamole capsules contains low-dose aspirin which is an nsaid (see clinical considerations) . in animal reproduction studies, there were adverse developmental effects with administration of aspirin in rats and rabbits at doses about 66 and 44 times, respectively, the human exposure at the maximum recommended daily dose of aspirin-dipyridamole. reproduction studies with dipyridamole in mice, rabbits, and rats have revealed no evidence of harm to the fetus up to doses about 25 times the maximum recommended daily human dose of aspirin-dipyridamole. nonclinical data are suggestive of a possible potentiation of aspirin-related fetal toxicity when combined with dipyridamole (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 labor and delivery aspirin and extended-release dipyridamole capsules, which contains dipyridamole and low-dose aspirin, increases the risk for bleeding [see error! hyperlink reference not valid. )]. maternal use of high-dose aspirin can result in excessive blood loss at delivery, prolonged gestation, prolonged labor, intracranial hemorrhage in premature infants, low birth weight, stillbirth, and neonatal death. data human data published data from clinical trials, observational studies, case series, and case reports over several decades have not identified a clear association between aspirin-dipyridamole use in pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. however, these studies cannot definitively establish the absence of any aspirin-dipyridamole associated risks. methodological limitations of these studies include variability in the timing and dose of drug exposure (e.g., most exposures occurred beyond the first trimester) and the small sample sizes of individual studies. animal data aspirin has been shown to be teratogenic in rats (spina bifida, exencephaly, microphthalmia and coelosomia) and rabbits (congested fetuses, agenesis of skull and upper jaw, generalized edema with malformation of the head, and diaphanous skin) at oral doses of 330 mg/kg/day and 110 mg/kg/day, respectively. these doses, which also resulted in a high resorption rate in rats (63% of implantations versus 5% in controls), are, on a mg/m2 basis, about 66 and 44 times, respectively, the dose of aspirin contained in the maximum recommended daily human dose of aspirin-dipyridamole. reproduction studies with dipyridamole have been performed in mice, rabbits and rats at oral doses of up to 125 mg/kg, 40 mg/kg, and 1000 mg/kg, respectively (about 1½, 2, and 25 times the maximum recommended daily human oral dose, respectively, on a mg/m2 basis) and have revealed no evidence of harm to the fetus due to dipyridamole. when 330 mg aspirin/kg/day was combined with 75 mg dipyridamole/kg/day in the rat at doses about 66 and 2 times, respectively, the maximum recommended daily human dose, the resorption rate approached 100%. risk summary based on data from a clinical lactation study in breastfeeding women taking low-dose aspirin, the metabolite salicylic acid is present in human milk in low levels (see data). dipyridamole is also present in human milk. there is no information on the effects of aspirin and extended-release dipyridamole capsules or dipyridamole on the breastfed infant or on milk production. there is insufficient information to determine the effects of aspirin on the breastfed infant and no information on the effects of aspirin on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for aspirin and extended-release dipyridamole capsules and any potential adverse effects on the breastfed child from aspirin and extended-release dipyridamole capsules or from the underlying maternal condition. data a published clinical study involved six exclusively breastfeeding women at 1 to 8 months postpartum who were taking 81 mg aspirin daily. milk samples were collected at steady state, at 0, 1, 2, 4, 8, 12, and 24 hours after taking a dose of aspirin. aspirin was undetectable in human milk. salicylic acid was present in milk at low levels (average concentration of 24 ng/ml). based on an average milk consumption of 150 ml/kg/day, the calculated relative infant dose was 0.4%. no adverse effects on the breastfed infants were noted. safety and effectiveness of aspirin and extended-release dipyridamole capsules in pediatric patients have not been studied. because of the aspirin component, use of this product in the pediatric population is not recommended [see error! hyperlink reference not valid. ]. of the total number of subjects in esps2, 61% were 65 and over, while 27% were 75 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see error! hyperlink reference not valid. ]. aspirin and extended-release dipyridamole capsules has not been studied in patients with hepatic or renal impairment. avoid using aspirin containing products, such as aspirin and extended-release dipyridamole capsules, in patients with severe hepatic or severe renal (glomerular filtration rate <10 ml/min) dysfunction [see warnings and precautions (error! hyperlink reference not valid. , error! hyperlink reference not valid. ) and error! hyperlink reference not valid. )].

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - dimethyl fumarate (unii: fo2303mni2) (monomethyl fumarate - unii:45iub1px8r) - dimethyl fumarate delayed-release capsules are indicated for the treatment of relapsing forms of multiple sclerosis (ms), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. dimethyl fumarate delayed-release capsules are contraindicated in patients with known hypersensitivity to dimethyl fumarate or to any of the excipients of dimethyl fumarate delayed-release capsules. reactions have included anaphylaxis and angioedema [see warnings and precautions (5.1)]. risk summary available data from the dimethyl fumarate delayed-release capsules pregnancy registry, observational studies, and pharmacovigilance with dimethyl fumarate use in pregnant women have not indicated an increased risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. most of the reported exposures to dimethyl fumarate occurred during the first trimester of pregnancy (see data) . in animals, adverse effects on offspring survival, growth, sexual maturation, and neurobehavioral function were observed when dimethyl fumarate (dmf) was administered during pregnancy and lactation at clinically relevant doses (see data). the 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. data human data in a prospective observational dimethyl fumarate delayed-release capsules pregnancy registry (2013 to 2022), the rate of major birth defects among 362 live births and stillbirths from women who were exposed to dimethyl fumarate during pregnancy was 3.6% (95% ci: 1.9-6.1). no specific pattern of major birth defects was identified. important potential study limitations include exposure misclassification, no adjustment for confounders, and lack of an internal comparator cohort. animal data in rats administered dmf orally (25, 100, 250 mg/kg/day) throughout organogenesis, embryofetal toxicity (reduced fetal body weight and delayed ossification) were observed at the highest dose tested. this dose also produced evidence of maternal toxicity (reduced body weight). plasma exposure (auc) for monomethyl fumarate (mmf), the major circulating metabolite, at the no-effect dose is approximately three times that in humans at the recommended human dose (rhd) of 480 mg/day. in rabbits administered dmf orally (25, 75, and 150 mg/kg/day) throughout organogenesis, embryolethality and decreased maternal body weight were observed at the highest dose tested. the plasma auc for mmf at the no-effect dose is approximately 5 times that in humans at the rhd. oral administration of dmf (25, 100, and 250 mg/kg/day) to rats throughout organogenesis and lactation resulted in increased lethality, persistent reductions in body weight, delayed sexual maturation (male and female pups), and reduced testicular weight at the highest dose tested. neurobehavioral impairment was observed at all doses. a no-effect dose for developmental toxicity was not identified. the lowest dose tested was associated with plasma auc for mmf lower than that in humans at the rhd. risk summary there are no data on the presence of dmf or mmf in human milk. the effects on the breastfed infant and on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for dimethyl fumarate delayed-release capsules and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. safety and effectiveness in pediatric patients have not been established. clinical studies of dimethyl fumarate did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

glenmark pharmaceuticals inc., usa - tacrolimus (unii: wm0haq4wnm) (tacrolimus anhydrous - unii:y5l2157c4j) - tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult patients receiving allogeneic kidney transplant [see clinical studies (14.1)] , liver transplant [see clinical studies (14.2)] and heart transplant [see clinical studies (14.3)] , and pediatric patients receiving allogeneic liver transplants [see clinical studies (14.2)] in combination with other immunosuppressants. additional pediatric use and lung transplant information is approved for astellas pharma us, inc.’s prograf (tacrolimus) products. however, due to astellas pharma us, inc.’s marketing exclusivity rights, this drug product is not labeled with that information. tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus. tacrolimus injection is contraindicated in patients with a hypersensitivity to hco-60 (polyoxyl 60 hydrogenated castor oil). hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [see adverse reactions (6)] . pregnan

Amerikas Savienotās Valstis - angļu - NLM (National Library of Medicine)

physicians total care, inc. - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine 150 mg - oxcarbazepine tablets are indicated for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and as monotherapy in the treatment of partial seizures in children aged 4 years and above with epilepsy, and as adjunctive therapy in children aged 2 years and above with partial seizures. oxcarbazepine tablets should not be used in patients with a known hypersensitivity to oxcarbazepine or to any of its components. oxcarbazepine levels may decrease during pregnancy [see warnings and precautions (5.10)]. there are no adequate and well-controlled clinical studies of oxcarbazepine in pregnant women; however, oxcarbazepine is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. given this fact, and the results of the animal studies described, it is likely that oxcarbazepine is a human teratogen. oxcarbazepine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. increased incidences of fetal s