Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - buspirone hydrochloride (unii: 207lt9j9oc) (buspirone - unii:tk65wks8hl) - buspirone hydrochloride 15 mg - buspirone hydrochloride tablets are indicated for the management of anxiety disorders or the short-term relief of the symptoms of anxiety. anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. the efficacy of buspirone hydrochloride tablets have been demonstrated in controlled clinical trials of outpatients whose diagnosis roughly corresponds to generalized anxiety disorder (gad). many of the patients enrolled in these studies also had coexisting depressive symptoms and buspirone hydrochloride tablets relieved anxiety in the presence of these coexisting depressive symptoms. the patients evaluated in these studies had experienced symptoms for periods of 1 month to over 1 year prior to the study, with an average symptom duration of 6 months. generalized anxiety disorder (300.02) is described in the american psychiatric association’s diagnostic and statistical manual, iii 1 as follows: generalized, persistent anxiety (of at least 1 month continual duration), manifested by symptoms from three of the four following categories: 1.      motor tension: shakiness, jitteriness, jumpiness, trembling, tension, muscle aches, fatigability, inability to relax, eyelid twitch, furrowed brow, strained face, fidgeting, restlessness, easy startle. 2.      autonomic hyperactivity: sweating, heart pounding or racing, cold, clammy hands, dry mouth, dizziness, lightheadedness, paresthesias (tingling in hands or feet), upset stomach, hot or cold spells, frequent urination, diarrhea, discomfort in the pit of the stomach, lump in the throat, flushing, pallor, high resting pulse and respiration rate. 3.      apprehensive expectation: anxiety, worry, fear, rumination, and anticipation of misfortune to self or others. 4.      vigilance and scanning: hyperattentiveness resulting in distractibility, difficulty in concentrating, insomnia, feeling "on edge," irritability, impatience. the above symptoms would not be due to another mental disorder, such as a depressive disorder or schizophrenia. however, mild depressive symptoms are common in gad. the effectiveness of buspirone hydrochloride tablets in long-term use, that is, for more than 3 to 4 weeks, has not been demonstrated in controlled trials. there is no body of evidence available that systematically addresses the appropriate duration of treatment for gad. however, in a study of long-term use, 264 patients were treated with buspirone hydrochloride tablets for 1 year without ill effect. therefore, the physician who elects to use buspirone hydrochloride tablets for extended periods should periodically reassess the usefulness of the drug for the individual patient. buspirone hydrochloride tablets are contraindicated in patients hypersensitive to buspirone hydrochloride. the use of monoamine oxidase inhibitors (maois) intended to treat depression with buspirone or within 14 days of stopping treatment with buspirone is contraindicated because of an increased risk of serotonin syndrome and/or elevated blood pressure. the use of buspirone within 14 days of stopping an maoi intended to treat depression is also contraindicated. starting buspirone in a patient who is being treated with reversible maois such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome. (see warnings , dosage and administration  and drug interactions ) controlled substance class: buspirone hydrochloride is not a controlled substance. physical and psychological dependence: in human and animal studies, buspirone has shown no potential for abuse or diversion and there is no evidence that it causes tolerance, or either physical or psychological dependence. human volunteers with a history of recreational drug or alcohol usage were studied in two double-blind clinical investigations. none of the subjects were able to distinguish between buspirone hydrochloride tablets and placebo. by contrast, subjects showed a statistically significant preference for methaqualone and diazepam. studies in monkeys, mice, and rats have indicated that buspirone lacks potential for abuse. following chronic administration in the rat, abrupt withdrawal of buspirone did not result in the loss of body weight commonly observed with substances that cause physical dependency. although there is no direct evidence that buspirone hydrochloride tablets causes physical dependence or drug-seeking behavior, it is difficult to predict from experiments the extent to which a cns-active drug will be misused, diverted, and/or abused once marketed. consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of buspirone hydrochloride tablets misuse or abuse (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - omeprazole (unii: kg60484qx9) (omeprazole - unii:kg60484qx9) - omeprazole delayed-release capsules are indicated for short-term treatment of active duodenal ulcer in adults. most patients heal within four weeks. some patients may require an additional four weeks of therapy. eradication of h. pylori has been shown to reduce the risk of duodenal ulcer recurrence. triple therapy omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate h. pylori in adults. dual therapy omeprazole delayed-release capsules in combination with clarithromycin are indicated for treatment of patients with h. pylori infection and duodenal ulcer disease to eradicate h. pylori in adults. among patients who fail therapy, omeprazole delayed-release capsules with clarithromycin are more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. in patients who fail therapy, susceptibility testing should be done. if resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see  clinical pharmacology (12.4) and the clarithromycin prescribing information, microbiology section ]. omeprazole delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults. omeprazole delayed-release capsules are indicated for the treatment of heartburn and other symptoms associated with gerd for up to 4 weeks in patients 2 years of age and older. pediatric patients 2 years of age to adults omeprazole delayed-release capsules are indicated for the short-term treatment (4 to 8 weeks) of ee due to acid-mediated gerd that has been diagnosed by endoscopy in patients 2 years of age and older. the efficacy of omeprazole delayed-release capsules used for longer than 8 weeks in patients with ee has not been established. if a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. if there is recurrence of ee or gerd symptoms (e.g., heartburn), additional 4 to 8 week courses of omeprazole delayed-release capsules may be considered. omeprazole delayed-release capsules are indicated for the maintenance healing of ee due to acid-mediated gerd in patients 2 years of age and older. controlled studies do not extend beyond 12 months. omeprazole delayed-release capsules are indicated for the long-term treatment of pathological hypersecretory conditions (e.g., zollinger-ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults. - omeprazole delayed-release capsules are contraindicated in patients with known hypersensitivity reactions including anaphylaxis to the formulation or any substituted benzimidazole. hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [ see warnings and precautions (5.2), adverse reactions (6)] . - proton pump inhibitors (ppis), including omeprazole delayed-release capsules, are contraindicated in patients receiving rilpivirine-containing products [see drug interactions (7)]. - for information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with omeprazole delayed-release capsules, refer to the contraindications section of their package inserts. risk summary there are no adequate and well-controlled studies with omeprazole in pregnant women. available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole (an enantiomer of omeprazole) magnesium in rats and rabbits during organogenesis with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole (based on body surface area for a 60 kg person). changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age [see data]. the estimated background risks of major birth defects and miscarriage for the indicated population 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. data human data four published epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to h 2 -receptor antagonists or other controls. a population-based retrospective cohort epidemiological study from the swedish medical birth registry, covering approximately 99% of pregnancies, from 1995 to 99, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. the number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low apgar score, or hospitalization was similar to the number observed in this population. the number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. a population-based retrospective cohort study covering all live births in denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. the overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. a retrospective cohort study reported on 689 pregnant women exposed to either h 2 -blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. the overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an h 2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. a small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). the reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired controls. rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birth weight were similar among the groups. several studies have reported no apparent adverse short-term effects on the infant when single dose oral or intravenous omeprazole was administered to over 200 pregnant women as premedication for cesarean section under general anesthesia. animal data omeprazole reproductive studies conducted with omeprazole in rats at oral doses up to 138 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) and in rabbits at doses up to 69.1 mg/kg/day (about 34 times an oral human dose of 40 mg on a body surface area basis) during organogenesis did not disclose any evidence for a teratogenic potential of omeprazole. in rabbits, omeprazole in a dose range of 6.9 to 69.1 mg/kg/day (about 3.4 to 34 times an oral human dose of 40 mg on a body surface area basis) administered during organogenesis produced dose-related increases in embryo-lethality, fetal resorptions, and pregnancy disruptions. in rats, dose-related embryo/fetal toxicity and postnatal developmental toxicity were observed in offspring resulting from parents treated with omeprazole at 13.8 to 138 mg/kg/day (about 3.4 to 34 times an oral human doses of 40 mg on a body surface area basis), administered prior to mating through the lactation period. esomeprazole the data described below was generated from studies using esomeprazole, an enantiomer of omeprazole. the animal to human dose multiples are based on the assumption of equal systemic exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg omeprazole. no effects on embryo-fetal development were observed in reproduction studies with esomeprazole magnesium in rats at oral doses up to 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) or in rabbits at oral doses up to 86 mg/kg/day (about 42 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis) administered during organogenesis. a pre- and postnatal developmental toxicity study in rats with additional endpoints to evaluate bone development was performed with esomeprazole magnesium at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). neonatal/early postnatal (birth to weaning) survival was decreased at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). body weight and body weight gain were reduced and neurobehavioral or general developmental delays in the immediate post-weaning timeframe were evident at doses equal to or greater than 69 mg/kg/day (about 17 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). in addition, decreased femur length, width and thickness of cortical bone, decreased thickness of the tibial growth plate and minimal to mild bone marrow hypocellularity were noted at doses equal to or greater than 14 mg/kg/day (about 3.4 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). physeal dysplasia in the femur was observed in offspring of rats treated with oral doses of esomeprazole magnesium at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). effects on maternal bone were observed in pregnant and lactating rats in the pre- and postnatal toxicity study when esomeprazole magnesium was administered at oral doses of 14 to 280 mg/kg/day (about 3.4 to 68 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). when rats were dosed from gestational day 7 through weaning on postnatal day 21, a statistically significant decrease in maternal femur weight of up to 14% (as compared to placebo treatment) was observed at doses equal to or greater than 138 mg/kg/day (about 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). a pre- and postnatal development study in rats with esomeprazole strontium (using equimolar doses compared to esomeprazole magnesium study) produced similar results in dams and pups as described above. a follow up developmental toxicity study in rats with further time points to evaluate pup bone development from postnatal day 2 to adulthood was performed with esomeprazole magnesium at oral doses of 280 mg/kg/day (about 68 times an oral human dose of 40 mg on a body surface area basis) where esomeprazole administration was from either gestational day 7 or gestational day 16 until parturition. when maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age. risk summary limited data suggest omeprazole may be present in human milk. there are no clinical data on the effects of omeprazole on the breastfed infant or on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for omeprazole and any potential adverse effects on the breastfed infant from omeprazole or from the underlying maternal condition. the safety and effectiveness of omeprazole have been established in pediatric patients 2 to 16 years for the treatment of symptomatic gerd, treatment of ee due to acid-mediated gerd, and maintenance of healing of ee due to acid-mediated gerd. use of omeprazole in this age group is supported by adequate and well-controlled studies in adults and uncontrolled safety, efficacy and pharmacokinetic studies performed in pediatric and adolescent patients [see clinical pharmacology (12.3), clinical studies (14.8)]. in the pediatric population, adverse reactions of the respiratory system were frequently reported in the entire (2 to 16 years) age group. accidental injuries were frequently reported in the 2 to 16 year age group [see adverse reactions (6.1)]. the safety and effectiveness of omeprazole have not been established in:  - patients less than 1 year of age for: treatment of symptomatic gerd maintenance of healing of ee due to acid-mediated gerd       - treatment of symptomatic gerd - maintenance of healing of ee due to acid-mediated gerd       - pediatric patients for: treatment of active duodenal ulcer h. pylori eradication to reduce the risk of duodenal ulcer recurrence treatment of active benign gastric ulcer pathological hypersecretory conditions - treatment of active duodenal ulcer - h. pylori eradication to reduce the risk of duodenal ulcer recurrence - treatment of active benign gastric ulcer - pathological hypersecretory conditions juvenile animal data esomeprazole, an enantiomer of omeprazole, was shown to decrease body weight, body weight gain, femur weight, femur length, and overall growth at oral doses about 34 to 68 times a daily human dose of 40 mg esomeprazole or 40 mg omeprazole based on body surface area in a juvenile rat toxicity study. the animal to human dose multiples are based on the assumption of equal systemic exposure to esomeprazole in humans following oral administration of either 40 mg esomeprazole or 40 mg omeprazole. a 28-day toxicity study with a 14-day recovery phase was conducted in juvenile rats with  esomeprazole magnesium at doses of 70 to 280 mg/kg/day (about 17 to 68 times a daily oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis). an increase in the number of deaths at the high dose of 280 mg/kg/day was observed when juvenile rats were administered esomeprazole magnesium from postnatal day 7 through postnatal day 35. in addition, doses equal to or greater than 140 mg/kg/day (about 34 times a daily oral human dose of 40 mg esomeprazole or 40 mg omeprazole on a body surface area basis), produced treatment-related decreases in body weight (approximately 14%) and body weight gain, decreases in femur weight and femur length, and affected overall growth. comparable findings described above have also been observed in this study with another esomeprazole salt, esomeprazole strontium, at equimolar doses of esomeprazole. omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the u.s. and europe. there were no differences in safety and effectiveness between the elderly and younger subjects. other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. the plasma clearance of omeprazole was 250 ml/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. however, no dosage adjustment is necessary in the elderly [see clinical pharmacology (12.3)] . in patients with hepatic impairment (child-pugh class a, b, or c) exposure to omeprazole substantially increased compared to healthy subjects. dosage reduction of omeprazole to 10 mg once daily is recommended for patients with hepatic impairment for maintenance of healing of ee [see dosage and administration (2.1), clinical pharmacology (12.3)] . in studies of healthy subjects, asians had approximately a four-fold higher exposure than caucasians. dosage reduction of omeprazole to 10 mg once daily is recommended for asian patients for maintenance of healing of ee [see dosage and administration (2.1) , clinical pharmacology (12.5)] . omeprazole delayed-release capsules, usp (oh mep' ra zole) omeprazole delayed-release capsules taking omeprazole delayed-release capsules with applesauce: 1. place 1 tablespoon of applesauce into a clean container. 2. carefully open the capsule and sprinkle the pellets onto the applesauce. mix the pellets with the applesauce. 3. swallow the applesauce and pellet mixture right away. do not chew or crush the pellets. do not store the applesauce and pellet mixture for later use.

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - naproxen sodium (unii: 9tn87s3a3c) (naproxen - unii:57y76r9atq) - naproxen sodium tablets are indicated for: the relief of the signs and symptoms of: - rheumatoid arthritis - osteoarthritis - ankylosing spondylitis - polyarticular juvenile idiopathic arthritis naproxen sodium tablets are also indicated for: the relief of signs and symptoms of: - tendonitis - bursitis - acute gout the management of: - pain - primary dysmenorrhea naproxen sodium tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen or any components of the drug product [see warnings and precautions (5.7, 5.9)] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7, 5.8)] - in the setting of coronary artery bypass graft (cabg) surgery

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - paroxetine hydrochloride hemihydrate (unii: x2els050d8) (paroxetine - unii:41vrh5220h) - paroxetine tablets are indicated in adults for the treatment of: - major depressive disorder (mdd) - obsessive compulsive disorder (ocd) - panic disorder (pd) - social anxiety disorder (sad) - generalized anxiety disorder (gad) - posttraumatic stress disorder (ptsd) paroxetine tablets are contraindicated in patients: - taking, or within 14 days of stopping, maois (including the maois linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see warnings and precautions ( 5.2), drug interactions ( 7)]. - taking thioridazine because of risk of qt prolongation [see warnings and precautions ( 5.3) and drug interactions ( 7)] - taking pimozide because of risk of qt prolongation [see warnings and precautions ( 5.3), drug interactions ( 7)]. - with known hypersensitivity (e.g., anaphylaxis, angioedema, stevens-johnson syndrome)

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - trazodone hydrochloride (unii: 6e8zo8lrnm) (trazodone - unii:ybk48bxk30) - trazodone hydrochloride tablets are indicated for the treatment of major depressive disorder (mdd) in adults. trazodone hydrochloride tablets are contraindicated in: - patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions ( 5.2), drug interactions ( 7.1)]. patients taking, or within 14 days of stopping, monoamine oxidase inhibitors (maois), including maois such as linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome [see warnings and precautions ( 5.2), drug interactions ( 7.1)]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. healthcare providers are encouraged to registe

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine tablets are indicated for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and as monotherapy in the treatment of partial-onset seizures in pediatric patients aged 4 years and above, and as adjunctive therapy in pediatric patients aged 2 years and above with partial-onset seizures. oxcarbazepine tablets are contraindicated in patients with a known hypersensitivity to oxcarbazepine or to any of its components, or to eslicarbazepine acetate [ see warnings and precautions (5.2, 5.3) ]. pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to aeds, such as oxcarbazepine tablets, during pregnancy. encourage women who are taking oxcarbazepine tablets during pregnancy to enroll in the north american antiepileptic drug (naaed) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. risk summary there are no adequate data on the developmental risks associated with the use of oxcarbazepine tablets in pregnant women; however, oxcarbazepine tablets is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. data on a limited number of pregnancies from pregnancy registries suggest that oxcarbazepine tablets monotherapy use is associated with congenital malformations (e.g., craniofacial defects such as oral clefts, and cardiac malformations such as ventricular septal defects). increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (mhd) during pregnancy at doses similar to the maximum recommended human dose (mrhd). in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. the background risk of major birth defects and miscarriage for the indicated population is unknown. clinical considerations an increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. monitor patients carefully during pregnancy and through the postpartum period [see warnings and precautions (5.10)] . data human data data from published registries have reported craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects in children with prenatal oxcarbazepine exposure. animal data when pregnant rats were given oxcarbazepine (0, 30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the mrhd on a mg/m 2 basis). increased embryofetal death and decreased fetal body weights were seen at the high dose. doses ≥300 mg/kg/day were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects. in a study in which pregnant rabbits were orally administered mhd (0, 20, 100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the mrhd on a mg/m 2 basis). this dose produced only minimal maternal toxicity. in a study in which female rats were dosed orally with oxcarbazepine (0, 25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (less than the mrhd on a mg/m 2 basis). oral administration of mhd (0, 25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the mrhd on a mg/m 2 basis). risk summary oxcarbazepine and its active metabolite (mhd) are present in human milk after oxcarbazepine tablets administration. the effects of oxcarbazepine and its active metabolite (mhd) on the breastfed infant or on milk production are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for oxcarbazepine tablets and any potential adverse effects on the breastfed infant from oxcarbazepine tablets or from the underlying maternal condition. contraception use of oxcarbazepine tablets with hormonal contraceptives containing ethinylestradiol or levonorgestrel is associated with decreased plasma concentrations of these hormones and may result in a failure of the therapeutic effect of the oral contraceptive drug. advise women of reproductive potential taking oxcarbazepine tablets who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control [see drug interactions (7.3)and clinical pharmacology (12.3)] . oxcarbazepine tablets is indicated for use as adjunctive therapy for partial-onset seizures in patients aged 2 to 16 years. the safety and effectiveness for use as adjunctive therapy for partial-onset seizures in pediatric patients below the age of 2 have not been established. oxcarbazepine tablets is also indicated as monotherapy for partial-onset seizures in patients aged 4 to 16 years. the safety and effectiveness for use as monotherapy for partial-onset seizures in pediatric patients below the age of 4 have not been established. oxcarbazepine tablets has been given to 898 patients between the ages of 1 month to 17 years in controlled clinical trials (332 treated as monotherapy) and about 677 patients between the ages of 1 month to 17 years in other trials [ see warnings and precautions (5.11), adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14) ]. there were 52 patients over age 65 in controlled clinical trials and 565 patients over the age of 65 in other trials. following administration of single (300 mg) and multiple (600 mg/day) doses of oxcarbazepine tablets in elderly volunteers (60 to 82 years of age), the maximum plasma concentrations and auc values of mhd were 30% to 60% higher than in younger volunteers (18 to 32 years of age). comparisons of creatinine clearance in young and elderly volunteers indicate that the difference was due to age-related reductions in creatinine clearance. close monitoring of sodium levels is required in elderly patients at risk for hyponatremia [ see warnings and precautions (5.1) ]. dose adjustment is recommended for renally impaired patients (clcr <30 ml/min) [ see dosage and administration (2.7)and clinical pharmacology (12.3) ]. the abuse potential of oxcarbazepine tablets has not been evaluated in human studies. intragastric injections of oxcarbazepine to 4 cynomolgus monkeys demonstrated no signs of physical dependence as measured by the desire to self-administer oxcarbazepine by lever pressing activity.

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - levetiracetam (unii: 44yrr34555) (levetiracetam - unii:44yrr34555) - levetiracetam tablet is indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children 1 month of age and older with epilepsy. levetiracetam tablet is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy. levetiracetam tablet is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy. levetiracetam tablets are contraindicated in patients with a hypersensitivity to levetiracetam. reactions have included anaphylaxis and angioedema [ see warnings and precautions ( 5.4) ]. levetiracetam blood levels may decrease during pregnancy [ see warnings and precautions ( 5.10)]. pregnancy category c there are no adequate and controlled studies in pregnant women. in animal studies, levetiracetam produced evidence of developmental toxicity, including teratogenic effects, at doses similar to or greater than human therapeutic doses. levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. oral administration of levetiracetam to female rats throughout pregnancy and lactation led to increased incidences of minor fetal skeletal abnormalities and retarded offspring growth pre- and/or postnatally at doses ≥350 mg/kg/day (equivalent to the maximum recommended human dose of 3,000 mg [mrhd] on a mg/m 2 basis) and with increased pup mortality and offspring behavioral alterations at a dose of 1,800 mg/kg/day (6 times the mrhd on a mg/m 2 basis). the developmental no effect dose was 70 mg/kg/day (0.2 times the mrhd on a mg/m 2 basis). there was no overt maternal toxicity at the doses used in this study. oral administration of levetiracetam to pregnant rabbits during the period of organogenesis resulted in increased embryofetal mortality and increased incidences of minor fetal skeletal abnormalities at doses ≥600 mg/kg/day (4 times mrhd on a mg/m 2 basis) and in decreased fetal weights and increased incidences of fetal malformations at a dose of 1,800 mg/kg/day (12 times the mrhd on a mg/m 2 basis). the developmental no effect dose was 200 mg/kg/day (equivalent to the mrhd on a mg/m 2 basis). maternal toxicity was also observed at 1,800 mg/kg/day. when levetiracetam was administered orally to pregnant rats during the period of organogenesis, fetal weights were decreased and the incidence of fetal skeletal variations was increased at a dose of 3,600 mg/kg/day (12 times the mrhd). 1,200 mg/kg/day (4 times the mrhd) was a developmental no effect dose. there was no evidence of maternal toxicity in this study. treatment of rats with levetiracetam during the last third of gestation and throughout lactation produced no adverse developmental or maternal effects at doses of up to 1,800 mg/kg/day (6 times the mrhd on a mg/m 2 basis). pregnancy registry to provide information regarding the effects of in utero exposure to levetiracetam, physicians are advised to recommend that pregnant patients taking levetiracetam enroll in the north american antiepileptic drug (naaed) pregnancy registry. this can be done by calling the toll free number 1-888-233-2334, and must be done by the patients themselves. information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. the effect of levetiracetam on labor and delivery in humans is unknown. levetiracetam is excreted in human milk. because of the potential for serious adverse reactions in nursing infants from levetiracetam, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. the safety and effectiveness of levetiracetam in the adjunctive treatment of partial onset seizures in pediatric patients age 1 month to 16 years old with epilepsy have been established [ see clinical studies ( 14.1) ]. the dosing recommendation in these pediatric patients varies according to age group and is weight-based [ see dosage and administration ( 2.2) ]. the safety and effectiveness of levetiracetam as adjunctive treatment of myoclonic seizures in adolescents 12 years of age and older with juvenile myoclonic epilepsy have been established [ see clinical studies ( 14.2) ]. the safety and effectiveness of levetiracetam as adjunctive therapy in the treatment of primary generalized tonic­clonic seizures in pediatric patients 6 years of age and older with idiopathic generalized epilepsy have been established [ see clinical studies ( 14.3) ]. a 3-month, randomized, double-blind, placebo-controlled study was performed to assess the neurocognitive and behavioral effects of levetiracetam as adjunctive therapy in 98 (levetiracetam n=64, placebo n=34) pediatric patients, ages 4 to 16 years old, with partial seizures that were inadequately controlled. the target dose was 60 mg/kg/day. neurocognitive effects were measured by the leiter-r attention and memory (am) battery, which measures various aspects of a child's memory and attention. although no substantive differences were observed between the placebo and drug treated groups in the median change from baseline in this battery, the study was not adequate to assess formal statistical non-inferiority of the drug and placebo. the achenbach child behavior checklist (cbcl/6 to 18), a standardized validated tool used to assess a child's competencies and behavioral/emotional problems, was also assessed in this study. an analysis of the cbcl/6 to 18 indicated on average a worsening in levetiracetam-treated patients in aggressive behavior, one of the eight syndrome scores [ see warnings and precautions ( 5.1) ]. studies of levetiracetam in juvenile rats (dosing from day 4 through day 52 of age) and dogs (dosing from week 3 through week 7 of age) at doses of up to 1,800 mg/kg/day (approximately 7 and 24 times, respectively, the maximum recommended pediatric dose of 60 mg/kg/day on a mg/m 2 basis) did not indicate a potential for age-specific toxicity. there were 347 subjects in clinical studies of levetiracetam that were 65 and over. no overall differences in safety were observed between these subjects and younger subjects. there were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the effectiveness of levetiracetam in these patients. levetiracetam is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [ see clinical pharmacology ( 12.3) ]. clearance of levetiracetam is decreased in patients with renal impairment and is correlated with creatinine clearance [ see clinical pharmacology ( 12.3) ]. dose adjustment is recommended for patients with impaired renal function and supplemental doses should be given to patients after dialysis [ see dosage and administration ( 2.5) ].

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - levofloxacin (unii: 6gnt3y5lmf) (levofloxacin anhydrous - unii:rix4e89y14) - levofloxacin tablets are indicated in adult patients for the treatment of nosocomial pneumonia due to methicillin-susceptible staphylococcus aureus, pseudomonas aeruginosa, serratia marcescens, escherichia coli,  klebsiella pneumoniae, haemophilus influenzae, or streptococcus pneumoniae. adjunctive therapy should be used as clinically indicated. where pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see clinical studies ( 14.1)]. levofloxacin tablets are indicated in adult patients for the treatment of community-acquired pneumonia due to methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae (including  multi-drug-resistant streptococcus pneumoniae [mdrsp]), haemophilus influenzae, haemophilus parainfluenzae, klebsiella pneumoniae, moraxella catarrhalis, chlamydophila pneumoniae, legionella pneumophila, or mycoplasma pneumoniae [see dosage and administration ( 2.1) and clinical studies ( 14.2)]. mdrsp isolates are isolates resistant to two or more of the following antibacterials: penicillin (mic ≥2 mcg/ml), 2 nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole. levofloxacin tablets are indicated in adult patients for the treatment of community-acquired pneumonia due to streptococcus pneumoniae (excluding multi-drug-resistant isolates [mdrsp]),  haemophilus influenzae, haemophilus parainfluenzae, mycoplasma pneumoniae, or chlamydophila pneumoniae [see dosage and administration ( 2.1) and clinical studies ( 14.3)].  levofloxacin tablets are indicated in adult patients for the treatment of complicated skin and skin structure infections due to methicillin-susceptible staphylococcus aureus, enterococcus faecalis, streptococcus pyogenes, or proteus mirabilis [see clinical studies ( 14.5)]. levofloxacin tablets are indicated in adult patients for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to methicillin-susceptible staphylococcus aureus, or streptococcus pyogenes. levofloxacin tablets are indicated in adult patients for the treatment of chronic bacterial prostatitis due to escherichia coli, enterococcus faecalis, or methicillin-susceptible staphylococcus epidermidis [see clinical studies ( 14.6)]. levofloxacin tablets are indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized bacillus anthracis in adults and pediatric patients, 6 months of age and older [see dosage and administration ( 2.2)].  the effectiveness of levofloxacin tablets is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. levofloxacin tablets have not been tested in humans for the post-exposure prevention of inhalation anthrax. the safety of levofloxacin tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. prolonged levofloxacin tablets therapy should only be used when the benefit outweighs the risk [see clinical studies ( 14.9 )]. levofloxacin tablets are indicated for treatment of plague, including pneumonic and septicemic plague, due to yersinia pestis ( y. pestis ) and prophylaxis for plague in adults and pediatric patients, 6 months of age and older [see dosage and administration ( 2.2)]. efficacy studies of levofloxacin tablets could not be conducted in humans with plague for ethical and feasibility reasons. therefore, approval of this indication was based on an efficacy study conducted in animals [see clinical studies ( 14.10)]. levofloxacin tablets are indicated in adult patients for the treatment of complicated urinary tract infections due to escherichia coli, klebsiella pneumoniae, or proteus mirabilis [see clinical studies ( 14.7)].  levofloxacin tablets are indicated in adult patients for the treatment of complicated urinary tract infections (mild to moderate) due to enterococcus faecalis, enterobacter cloacae, escherichia coli, klebsiella pneumoniae, proteus mirabilis, or pseudomonas aeruginosa [see clinical studies (14.8) ]. levofloxacin tablets are indicated in adult patients for the treatment of acute pyelonephritis caused by escherichia coli, including cases with concurrent bacteremia [see clinical studies (14.7, 14.8)]. levofloxacin tablets are indicated in adult patients  for the treatment of uncomplicated urinary tract infections (mild to moderate) due to escherichia coli, klebsiella pneumoniae, or staphylococcus saprophyticus. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1 to  5.15 )] and for some patients uncomplicated urinary tract infection is self-limiting, reserve levofloxacin tablets for treatment of uncomplicated urinary tract infections in patients who have no alternative treatment options. levofloxacin tablets are indicated in adult patients for the treatment of acute bacterial exacerbation of chronic bronchitis (abecb) due to methicillin-susceptible staphylococcus aureus, streptococcus pneumoniae, haemophilus influenzae, haemophilus parainfluenzae, or moraxella catarrhalis. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1to  5.15 )] and for some patients abecb is self-limiting, reserve levofloxacin tablets for treatment of abecb in patients who have no alternative treatment options. levofloxacin tablets are indicated in adult patients for the treatment of acute bacterial sinusitis (abs) due to streptococcus pneumoniae, haemophilus influenzae, or moraxella catarrhalis [see clinical studies ( 14.4)]. because fluoroquinolones, including levofloxacin tablets, have been associated with serious adverse reactions [see warnings and precautions ( 5.1to  5.15)] and for some patients abs is self-limiting, reserve levofloxacin tablets for treatment of abs in patients who have no alternative treatment options. to reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin tablets and other antibacterial drugs, levofloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. when culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. in the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. culture and susceptibility testing appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see microbiology ( 12.4)] . therapy with levofloxacin tablets may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected. as with other drugs in this class, some isolates of pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin tablets. culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance. levofloxacin tablets are contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see warnings and precautions ( 5.3)]. risk summary published information from case reports, case control studies and observational studies on levofloxacin administered during pregnancy have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. in animal reproduction studies, oral administration of levofloxacin to pregnant rats and rabbits during organogenesis at doses up to 9.4 times and 1.1 times the maximum recommended human dose (mrhd), respectively, did not result in teratogenicity. fetal toxicity was seen in the rat study, but was absent at doses up to 1.2 times the maximum recommended human dose (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 risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.  data animal data levofloxacin was not teratogenic in an embryofetal development study in rats treated during organogenesis with oral doses as high as 810 mg/kg/day which corresponds to 9.4 times the mrhd (based upon doses normalized for total body surface area). the oral dose of 810 mg/kg/day (high dose) to rats caused decreased fetal body weight and increased fetal mortality that was not seen at the next lower dose (mid-dose, 90 mg/kg/day, equivalent to 1.2 times the mrhd (based upon doses normalized for total body surface area). maternal toxicity was limited to lower weight gain in the mid and high dose groups. no teratogenicity was observed in an embryofetal development study in rabbits dosed orally during organogenesis with doses as high as 50 mg/kg/day, which corresponds to 1.1 times the mrhd (based upon doses normalized for total body surface area). maternal toxicity at that dose consisted of lower weight gain and decreased food consumption relative to controls and abortion in four of sixteen dams. risk summary published literature reports that levofloxacin is present in human milk following intravenous and oral administration ( see data ). there is no information regarding effects of levofloxacin on milk production or the breastfed infant. because of the potential risks of serious adverse reactions, in breastfed infants, for most indications, a lactating woman may consider pumping and discarding breast milk during treatment with levofloxacin and an additional two days (five half-lives) after the last dose. alternatively, advise a lactating woman that breastfeeding is not recommended during treatment with levofloxacin and for an additional two days (five half-lives) after the last dose [see use in specific populations (8.4) and clinical pharmacology (12.3)] . however, for inhalation anthrax (post exposure), during an incident resulting in exposure to anthrax, the risk-benefit assessment of continuing breastfeeding while the mother (and potentially the infant) is (are) on levofloxacin may be acceptable [see dosage and administration (2.2), pediatric use (8.4), and clinical studies (14.2)]. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for levofloxacin and any potential adverse effects on the breastfed child from levofloxacin or from the underlying maternal condition. data a published literature reports that peak levofloxacin human milk concentration was 8.2 mg/l at 5 hours after dosing in a woman who received 500 mg of intravenous, followed by oral, levofloxacin daily. for an infant fed exclusively with human milk (approximately 900 ml/day), an estimated maximum daily dose of levofloxacin through breastfeeding is 5 mg (i.e., approximately 1% of maternal daily dose). the above data come from a single case and may not be generalizable to the general population of lactating women. quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species. [see warnings and precautions ( 5.12) and animal toxicology and/or pharmacology ( 13.2)]. inhalational anthrax (post-exposure) levofloxacin is indicated in pediatric patients 6 months of age and older, for inhalational anthrax (post-exposure). the risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate. the safety of levofloxacin in pediatric patients treated for more than 14 days has not been studied [see indications and usage (1.7),   dosage and administration ( 2.2 ) and clinical studies ( 14.9)]. plague levofloxacin is indicated in pediatric patients, 6 months of age and older, for treatment of plague, including pneumonic and septicemic plague due to yersinia pestis (y. pestis) and prophylaxis for plague. efficacy studies of levofloxacin could not be conducted in humans with pneumonic plague for ethical and feasibility reasons. therefore, approval of this indication was based on an efficacy study conducted in animals. the risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate [see indications and usage ( 1.8),  dosage and administration ( 2.2)  and clinical studies ( 14.10 )]. safety and effectiveness of levofloxacin in pediatric patients below the age of six months have not been established. pharmacokinetics following intravenous administration the pharmacokinetics of levofloxacin following a single intravenous dose were investigated in pediatric patients ranging in age from six months to 16 years. pediatric patients cleared levofloxacin faster than adult patients resulting in lower plasma exposures than adults for a given mg/kg dose [see clinical pharmacology ( 12.3) and clinical studies ( 14.9) ]. dosage in pediatric patients with inhalational anthrax or plague for the recommended levofloxacin tablet dosage in pediatric patients with inhalational anthrax or plague, see dosage and administration ( 2.2 ). levofloxacin tablets cannot be administered to pediatric patients who weigh less than 30 kg because of the limitations of the available strengths. alternative formulations of levofloxacin may be considered for pediatric patients who weigh less than 30 kg. adverse reactions in clinical trials, 1,534 pediatric patients (6 months to 16 years of age) were treated with oral and intravenous levofloxacin. pediatric patients 6 months to 5 years of age received levofloxacin 10 mg/kg twice a day and pediatric patients greater than 5 years of age received 10 mg/kg once a day (maximum 500 mg per day) for approximately 10 days. levofloxacin tablets can only be administered to pediatric patients with inhalational anthrax (post-exposure) or plague who are 30 kg or greater due to the limitations of the available strengths [see dosage and administration ( 2.2)]. a subset of pediatric patients in the clinical trials (1,340 levofloxacin-treated and 893 non-fluoroquinolone-treated) enrolled in a prospective, long-term surveillance study to assess the incidence of protocol-defined musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) during 60 days and 1 year following the first dose of the study drug. pediatric patients treated with levofloxacin had a significantly higher incidence of musculoskeletal disorders when compared to the non-fluoroquinolone-treated children as illustrated in table 7. levofloxacin tablets can only be administered to pediatric patients with inhalational anthrax (post-exposure) or plague who are 30 kg or greater due to the limitations of the available strengths [see dosage and administration ( 2.2 )]. table 7:  incidence of musculoskeletal disorders in pediatric clinical trial * non-fluoroquinolone: ceftriaxone, amoxicillin/clavulanate, clarithromycin † 2-sided fisher's exact test  ‡  there were 1,199 levofloxacin-treated and 804 non-fluoroquinolone-treated pediatric patients who had a one-year evaluation visit. however, the incidence of musculoskeletal disorders was calculated using all reported events during the specified period for all pediatric patients enrolled regardless of whether they completed the 1-year evaluation visit. arthralgia was the most frequently occurring musculoskeletal disorder in both treatment groups. most of the musculoskeletal disorders in both groups involved multiple weight-bearing joints. disorders were moderate in 8/46 (17%) children and mild in 35/46 (76%) levofloxacin-treated pediatric patients and most were treated with analgesics. the median time to resolution was 7 days for levofloxacin-treated pediatric patients and 9 for non-fluoroquinolone-treated children (approximately 80% resolved within 2 months in both groups). no pediatric patient had a severe or serious disorder and all musculoskeletal disorders resolved without sequelae. vomiting and diarrhea were the most frequently reported adverse reactions, occurring in similar frequency in the levofloxacin-treated and non-fluoroquinolone-treated pediatric patients. in addition to the adverse reactions reported in pediatric patients in clinical trials, adverse reactions reported in adults during clinical trials or post-marketing experience [see adverse reactions ( 6)] may also be expected to occur in pediatric patients. geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as levofloxacin. this risk is further increased in patients receiving concomitant corticosteroid therapy. tendinitis or tendon rupture can involve the achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. caution should be used when prescribing levofloxacin to elderly patients especially those on corticosteroids. patients should be informed of this potential side effect and advised to discontinue  levofloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see boxed warning; warnings and precautions ( 5.2); and adverse reactions ( 6.3)]. in phase 3 clinical trials, 1,945 levofloxacin-treated patients (26%) were ≥ 65 years of age. of these, 1,081 patients (14%) were between the ages of 65 and 74 and 864 patients (12%) were 75 years or older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. severe, and sometimes fatal, cases of hepatotoxicity have been reported post-marketing in association with levofloxacin. the majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see warnings and precautions ( 5.8)]. epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see warnings and precautions ( 5.9)]. elderly patients may be more susceptible to drug-associated effects on the qt interval. therefore, precaution should be taken when using levofloxacin with concomitant drugs that can result in prolongation of the qt interval (e.g., class ia or class iii antiarrhythmics) or in patients with risk factors for torsade de pointes (e.g., known qt prolongation, uncorrected hypokalemia) [see warnings and precautions ( 5.11)]. the pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. however, since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [ see clinical pharmacology ( 12.3)]. clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with renal impairment (creatinine clearance < 50 ml/min), requiring dosage adjustment in such patients to avoid accumulation. neither hemodialysis nor continuous ambulatory peritoneal dialysis (capd) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or capd [see dosage and administration ( 2.3)]. pharmacokinetic studies in patients with hepatic impairment have not been conducted. due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - aripiprazole (unii: 82vfr53i78) (aripiprazole - unii:82vfr53i78) - aripiprazole oral 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/m 2  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/m 2 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/m 2 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 rats injected intravenously with aripiprazole during organogenesis at doses of 3, 9, and 27 mg/kg/day, which are 1, 3, and 9 times the mrhd of 30 mg/day based on mg/m 2 body surface area, decreased fetal weight and delayed skeletal ossification were observed at 9 times the mrhd; this dose also caused 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/m 2 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 pregnant rabbits injected intravenously with aripiprazole during organogenesis at doses of 3, 10, and 30 mg/kg/day, which are 2, 6, and 19 times the mrhd of 30 mg/day based on mg/m 2 body surface area, decreased fetal weight, increased fetal abnormalities (primarily skeletal), and decreased fetal skeletal ossification were observed at 19 times the mrhd; this dose also caused maternal toxicity. the fetal no-effect dose was 10 mg/kg/day, which is 6 times the mrhd. in rats treated orally with aripiprazole peri- and post-natally 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/m 2 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. in rats injected intravenously with aripiprazole from gestation day 6 through lactation day 20 at doses of 3, 8, and 20 mg/kg/day, which are 1, 3, and 6 times the mrhd of 30 mg/day based on mg/m 2 body surface area, increased stillbirths were observed at 3 and 6 times the mrhd; and decreases in early postnatal pup weight and survival were observed at 6 times the mrhd; these doses also caused some maternal toxicity. there were no effects on postnatal behavioral and reproductive development. 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 (auc 0-24 ) 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 (auc 0-24 ) 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.

Amerika Syarikat - Inggeris - NLM (National Library of Medicine)

remedyrepack inc. - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j) - tramadol hydrochloride tablets are indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see warnings and precautions (5.1)] , reserve tramadol hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: - have not been tolerated or are not expected to be tolerated. - have not provided adequate analgesia or are not expected to provide adequate analgesia. tramadol hydrochloride tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions (5.4)]. - postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions (5.4)]. tramadol hydrochloride tablets are also contrain