미국 - 영어 - NLM (National Library of Medicine)

amneal pharmaceuticals llc - oxcarbazepine (unii: vzi5b1w380) (oxcarbazepine - unii:vzi5b1w380) - oxcarbazepine 300 mg in 5 ml - oxcarbazepine oral suspension is 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 oral suspension is 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, during pregnancy. encourage women who are taking oxcarbazepine 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 in pregnant women; however, oxcarbazepine 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 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% to 4% and 15% to 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)]. d ata 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 1,000 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/m2 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/m2 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/m2 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/m2 basis). risk summary oxcarbazepine and its active metabolite (mhd) are present in human milk after oxcarbazepine 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 and any potential adverse effects on the breastfed infant from oxcarbazepine or from the underlying maternal condition. contraception use of oxcarbazepine 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 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 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 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 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 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 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. oxcarbazepine oral suspension (300 mg/5 ml) each 5 ml contains 300 mg oxcarbazepine read these instructions carefully to learn how to use the medicine dispensing system correctly. 1. a plastic adapter that you push into the neck of the bottle the first time that you open the bottle. the adapter must always stay in the bottle. 2. a bottle containing 250 ml of the medicine, with a child-resistant cap. always replace the cap after use. 3. a 10 ml oral dosing syringe that fits into the plastic adapter to withdraw the prescribed dose of medicine from the bottle. 1. shake the bottle of medicine for at least 10 seconds . 2. remove the child-resistant cap by pushing it firmly down and turning it counter clockwise – to the left (as shown on the top of the cap). note: save the cap so you can close the bottle after each use. 3. hold the open bottle upright on a table and push the plastic adapter firmly into the neck of the bottle as far as you can. 4. replace the cap to be sure that the adapter has been fully forced into the neck of the bottle. note: you may not be able to push the adapter fully down, but it will be forced into the bottle when you screw the cap back on. now the bottle is ready to use with the syringe. the adapter must always stay in the bottle. the child-resistant cap should seal the bottle in between use. 1. shake the bottle well. prepare the dose right away. 2. push and turn the child-resistant cap to open the bottle. note: always replace the cap after use. 3. check that the plunger is all the way down inside the barrel of the syringe. 4. keep the bottle upright and push the syringe firmly into the plastic adapter. 5. hold the syringe in place and carefully turn the bottle upside down. 6. slowly pull the plunger out so that the syringe fills with some medicine. push the plunger back in just far enough to completely push out any large air bubbles that may be trapped in the syringe. 7. slowly pull the plunger out until the top edge of the plunger is exactly level with the marker on the syringe barrel for the prescribed dose. note: if the prescribed dose is more than 10 ml, you will need to refill the syringe to make up the full dose. 8. carefully turn the bottle upright. take out the syringe by gently twisting it out of the plastic adapter. the plastic adapter should stay in the bottle. 9. you can mix the dose of medicine in a small glass of water before it is swallowed, or you can drink it directly from the syringe. a. if you mix the medicine with water, add some water to a glass. push in the plunger on the syringe all the way to empty all the medicine into the glass. stir the medicine in the water and drink it all. b. if you use the syringe to take the medicine, the patient must sit upright. push the plunger slowly to let the patient swallow the medicine. 10. replace the child-resistant cap after use. cleaning: after use, rinse the syringe with warm water and allow it to dry thoroughly. distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 02-2019-02

미국 - 영어 - NLM (National Library of Medicine)

amneal pharmaceuticals llc - quinine sulfate (unii: kf7z0e0q2b) (quinine - unii:a7v27phc7a) - quinine sulfate 324 mg - quinine sulfate is an antimalarial drug indicated only for treatment of uncomplicated plasmodium falciparum malaria. quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented [see clinical studies (14)] . limitations of use: quinine sulfate capsules are not approved for: - treatment of severe or complicated p. falciparum malaria. - prevention of malaria. - treatment or prevention of nocturnal leg cramps [see warnings and precautions (5.1)] . quinine sulfate capsules are contraindicated in patients with the following: - prolonged qt interval. one case of a fatal ventricular arrhythmia was reported in an elderly patient with a prolonged qt interval at baseline, who received quinine sulfate intravenously for p. falciparum malaria [see warnings and precautions (5.4)] . - known hypersensitivity reactions to quinine. these include, but are not limited to, the following [see warnings and precautions (5.7)] : thrombocytopenia idiopathic thrombocytopenia purpura (itp) and thrombotic thrombocytopenic purpura (ttp) hemolytic uremic syndrome (hus) blackwater fever (acute intravascular hemolysis, hemoglobinuria, and hemoglobinemia) - thrombocytopenia - idiopathic thrombocytopenia purpura (itp) and thrombotic thrombocytopenic purpura (ttp) - hemolytic uremic syndrome (hus) - blackwater fever (acute intravascular hemolysis, hemoglobinuria, and hemoglobinemia) - known hypersensitivity to mefloquine or quinidine: cross-sensitivity to quinine has been documented [see warnings and precautions (5.7)] . - myasthenia gravis. quinine has neuromuscular blocking activity, and may exacerbate muscle weakness. - optic neuritis. quinine may exacerbate active optic neuritis [see adverse reactions (6.1)] . risk summary prolonged experience with quinine in pregnant women over several decades, based on published prospective and retrospective observational studies, surveys, safety and efficacy studies, review articles, case reports and case series have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see data) . in animal reproduction studies, administration of quinine by multiple routes of administration to pregnant rabbits, dogs, guinea pigs, rats, and monkeys during the period of organogenesis at doses of 0.25 to 2 times the maximum recommended human dose (mrhd) based on body surface area (bsa), produced embryo-fetal toxicity including malformations. offspring of pregnant rats administered oral quinine sulfate during mating, gestation, and lactation at a dose approximately equivalent to 0.1 times the mrhd based on bsa comparison experienced impaired growth and delayed physical development (see data) . the estimated background risk 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. clinical considerations disease-associated maternal and/or embryo/fetal risk malaria during and after pregnancy increases the risk for adverse pregnancy and neonatal outcomes, including maternal anemia, severe malaria, spontaneous abortion, stillbirths, preterm delivery, low birth weight, intrauterine growth retardation, congenital malaria, and maternal and neonatal mortality. maternal adverse reactions an increased incidence of hypoglycemia, due to increased pancreatic secretion of insulin, has been reported with quinine use, in pregnant women, especially during the third trimester1 . monitor glucose levels in pregnant woman taking quinine. tinnitus, vomiting, dizziness, and nausea are commonly reported adverse reactions in pregnant women taking quinine. pregnant women are also at risk for a rare triad of complications: massive hemolysis, hemoglobinemia, and hemoglobinuria2 . labor or delivery in doses several times higher than those used to treat malaria, quinine may cause uterine contractions; however, there is no evidence that quinine causes uterine contractions at the doses recommended for the treatment of malaria. data human data quinine crosses the placenta with measurable blood concentrations in the fetus. in 8 women who delivered live infants 1 to 6 days after starting quinine therapy, umbilical cord plasma quinine concentrations were between 1.0 and 4.6 mg/l (mean 2.4 mg/l) and the mean (±sd) ratio of cord plasma to maternal plasma quinine concentrations was 0.32 ± 0.14. quinine levels in the fetus may not be therapeutic. adverse outcomes have been identified in the post-marketing experience with quinine during pregnancy. because these outcomes are reported from varied data sources and have inconsistent findings and/or important methodological limitations, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. in studies in which more than 893 pregnant women were treated with quinine for malaria in the first trimester, no quinine-associated increases in the incidence of congenital anomalies were observed compared with other antimalarial drugs3 . a retrospective study of women with p. falciparum malaria who were treated with oral quinine sulfate 10 mg/kg 3 times daily for 7 days at any time in pregnancy reported no significant difference in the rate of stillbirths at > 28 weeks of gestation in women treated with quinine (10 of 633 women [1.6%]) as compared with a control group without malaria or exposure to antimalarial drugs during pregnancy (40 of 2201 women [1.8%]). the overall rate of congenital malformations (9 of 633 offspring [1.4%]) was not different for women who were treated with quinine sulfate compared with the control group (38 of 2201 offspring [1.7%]). the spontaneous abortion rate was higher in the control group (10.9%) than in women treated with quinine sulfate (3.5%) [or = 3.1; 95% ci 2.1 to 4.7]. an epidemiologic survey that included 104 mother-child pairs exposed to quinine during the first 4 months of pregnancy, found no increased risk of structural birth defects was seen (2 fetal malformations [1.9%]). case reports describe deafness and optic nerve hypoplasia in children exposed in utero due to maternal ingestion of high doses of quinine. animal data in animal developmental studies conducted in multiple animal species4 , pregnant animals received quinine by the subcutaneous, intramuscular, and oral routes at doses 0.25 to 2 times the maximum recommended human dose (mrhd) based on body surface area (bsa). increases in fetal death were observed in utero in pregnant rabbits at maternal doses ≥ 100 mg/kg/day and in pregnant dogs at ≥ 15 mg/kg/day corresponding to dose levels approximately 0.5 and 0.25 times the mrhd respectively based on bsa comparisons. rabbit offspring had increased rates of degenerated auditory nerve and spiral ganglion and increased rates of cns anomalies such as anencephaly and microcephaly at a dose of 130 mg/kg/day corresponding to a maternal dose approximately 1.3 times the mrhd based on bsa comparison. guinea pig offspring had increased rates of cochlear hemorrhage at maternal doses of 200 mg/kg corresponding to a dose level of approximately 1.4 times the mrhd based on bsa comparison. no fetal malformations were observed in rats at maternal doses up to 300 mg/kg/day and in monkeys at maternal doses up to 200 mg/kg/day corresponding to doses approximately 1 and 2 times the mrhd respectively based on bsa comparisons. in a pre-postnatal study, pregnant rats received quinine sulfate in feed beginning two weeks prior to mating, through gestation, and lactation. an estimated oral dose of quinine sulfate of 20 mg/kg/day corresponding to approximately 0.1 times the mrhd based on bsa comparison resulted in offspring with impaired growth, lower body weights at birth and during the lactation period, and delayed physical development of teeth eruption and eye opening during the lactation period. risk summary quinine is present in human milk. it is estimated that breastfed infants would receive less than 2 to 3 mg per day of quinine base (< 0.4% of the maternal dose) via breast milk (see data) . there are no data on the effects of quinine 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 quinine sulfate and any potential adverse effects on the breastfed child from quinine sulfate or from the underlying maternal condition. data no toxicity was reported in infants in a single study where oral quinine sulfate (10 mg/kg every 8 hours for 1 to 10 days) was administered to 25 lactating women. quinine concentrations in breast milk are approximately 31% of quinine concentrations in maternal plasma. infertility in a published study5 in 5 men receiving oral tablets of 600 mg quinine three times a day for one week, sperm motility was decreased and percent sperm with abnormal morphology was increased, but sperm count and serum testosterone were unaffected. based on findings from animal studies, quinine sulfate may impair fertility [see nonclinical toxicology (13.1)] . the safety and efficacy of quinine sulfate in pediatric patients under the age of 16 has not been established. clinical studies of quinine sulfate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond to treatment differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. clearance of quinine is decreased in patients with severe chronic renal failure. the dosage and dosing frequency should be reduced [see dosage and administration (2.2) and clinical pharmacology (12.3)] . in patients with severe hepatic impairment (child-pugh c), quinine oral clearance (cl/f) is decreased, volume of distribution (vd /f) is increased, and half-life is prolonged, relative to subjects with normal liver function. therefore, quinine is not indicated in patients with severe hepatic impairment and alternate therapy should be administered [see dosage and administration (2.3) and clinical pharmacology (12.3)] . close monitoring is recommended for patients with mild (child-pugh a) or moderate (child-pugh b) hepatic impairment, as exposure to quinine may be increased relative to subjects with normal liver function [see clinical pharmacology (12.3)] .

오스트레일리아 - 영어 - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - cyproterone acetate, quantity: 100 mg - tablet, uncoated - excipient ingredients: lactose monohydrate; microcrystalline cellulose; croscarmellose sodium; povidone; magnesium stearate - inoperable prostatic carcinoma. to suppress flare with initial luteinising hormone releasing hormone (lhrh) analogue therapy; in long-term palliative treatment where lhrh analogues or surgery are ineffective, not tolerated, contraindicated or where oral therapy is preferred; in the treatment of hot flushes in patients treated with lhrh analogues or who have had orchidectomy.

오스트레일리아 - 영어 - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - cyproterone acetate -

미국 - 영어 - NLM (National Library of Medicine)

amneal pharmaceuticals llc - celecoxib (unii: jcx84q7j1l) (celecoxib - unii:jcx84q7j1l) - celecoxib capsules are indicated for: for the management of the signs and symptoms of oa [see clinical studies (14.1)] . for the management of the signs and symptoms of ra [see clinical studies (14.2)] . for the management of the signs and symptoms of jra in patients 2 years and older [see clinical studies (14.3)] . for the management of the signs and symptoms of as [see clinical studies (14.4)] . for the management of acute pain in adults [see clinical studies (14.5)] . for the management of primary dysmenorrhea [see clinical studies (14.5)] . celecoxib is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to celecoxib, 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 cabg surgery [see warnings and precautions (5.1)] . - in patients who have demonstrated allergic-type reactions to sulfonamides [see warnings and precautions (5.7)] . risk summary use of nsaids, including celecoxib, 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 celecoxib use between about 20 and 30 weeks of gestation and avoid celecoxib 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 celecoxib, 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, embryo-fetal deaths and an increase in diaphragmatic hernias were observed in rats administered celecoxib daily during the period of organogenesis at oral doses approximately 6 times the maximum recommended human dose (mrhd) of 200 mg twice daily. in addition, structural abnormalities (e.g., septal defects, ribs fused, sternebrae fused and sternebrae misshapen) were observed in rabbits given daily oral doses of celecoxib during the period of organogenesis at approximately 2 times the mrhd (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 celecoxib, 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 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 celecoxib, 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 celecoxib treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue celecoxib and follow up according to clinical practice (see data) . labor or delivery there are no studies on the effects of celecoxib during labor or delivery. in animal studies, nsaids, including celecoxib, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data human data the available data do not establish the presence or absence of developmental toxicity related to the use of celecoxib. 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 post-marketing 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 post-marketing 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 celecoxib at oral doses ≥ 150 mg/kg/day (approximately 2 times the human exposure at 200 mg twice daily as measured by auc0-24 ), caused an increased incidence of ventricular septal defects, a rare event, and fetal alterations, such as ribs fused, sternebrae fused and sternebrae misshapen when rabbits were treated throughout organogenesis. a dose-dependent increase in diaphragmatic hernias was observed when rats were given celecoxib at oral doses ≥ 30 mg/kg/day (approximately 6 times human exposure based on the auc0-24 at 200 mg twice daily for ra) throughout organogenesis. in rats, exposure to celecoxib during early embryonic development resulted in pre-implantation and post-implantation losses at oral doses ≥ 50 mg/kg/day (approximately 6 times human exposure based on the auc0-24 at 200 mg twice daily for ra). celecoxib produced no evidence of delayed labor or parturition at oral doses up to 100 mg/kg in rats (approximately 7-fold human exposure as measured by the auc0-24 at 200 mg twice daily). the effects of celecoxib on labor and delivery in pregnant women are unknown. risk summary limited data from 3 published reports that included a total of 12 breastfeeding women showed low levels of celecoxib in breast milk. the calculated average daily infant dose was 10 to 40 mcg/kg/day, less than 1% of the weight-based therapeutic dose for a two-year old-child. a report of two breastfed infants 17 and 22 months of age did not show any adverse events. caution should be exercised when celecoxib is administered to a nursing woman. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for celecoxib and any potential adverse effects on the breastfed infant from the celecoxib or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including celecoxib, 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 celecoxib, in women who have difficulties conceiving or who are undergoing investigation of infertility. celecoxib is approved for relief of the signs and symptoms of juvenile rheumatoid arthritis in patients 2 years and older. safety and efficacy have not been studied beyond six months in children. the long-term cardiovascular toxicity in children exposed to celecoxib has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to celecoxib or other cox-2 selective and non­-selective nsaids [see boxed warning, warnings and precautions (5.5), and clinical studies (14.3) ] . the use of celecoxib in patients 2 years to 17 years of age with pauciarticular, polyarticular course jra or in patients with systemic onset jra was studied in a 12-week, double-blind, active controlled, pharmacokinetic, safety and efficacy study, with a 12-week open-label extension. celecoxib has not been studied in patients under the age of 2 years, in patients with body weight less than 10 kg (22 lbs), and in patients with active systemic features. patients with systemic onset jra (without active systemic features) appear to be at risk for the development of abnormal coagulation laboratory tests. in some patients with systemic onset jra, both celecoxib and naproxen were associated with mild prolongation of activated partial thromboplastin time (aptt) but not prothrombin time (pt). when nsaids including celecoxib are used in patients with systemic onset jra, monitor patients for signs and symptoms of abnormal clotting or bleeding, due to the risk of disseminated intravascular coagulation. patients with systemic onset jra should be monitored for the development of abnormal coagulation tests [see dosage and administration (2.4), warnings and precautions (5.15), adverse reactions (6.1), animal toxicology (13.2), clinical studies (14.3)]. alternative therapies for treatment of jra should be considered in pediatric patients identified to be cyp2c9 poor metabolizers [see poor metabolizers of cyp2c9 substrates (8.8)] . 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)] . of the total number of patients who received celecoxib in pre-approval clinical trials, more than 3,300 were 65 to 74 years of age, while approximately 1,300 additional patients were 75 years and over. no substantial differences in effectiveness were observed between these subjects and younger subjects. in clinical studies comparing renal function as measured by the gfr, bun and creatinine, and platelet function as measured by bleeding time and platelet aggregation, the results were not different between elderly and young volunteers. however, as with other nsaids, including those that selectively inhibit cox-2, there have been more spontaneous post-marketing reports of fatal gi events and acute renal failure in the elderly than in younger patients [see warnings and precautions (5.2, 5.6)] . the daily recommended dose of celecoxib capsules in patients with moderate hepatic impairment (child-pugh class b) should be reduced by 50%. the use of  celecoxib in patients with severe hepatic impairment is not recommended [see dosage and administration (2.7)  and clinical pharmacology (12.3)] . celecoxib is not recommended in patients with severe renal insufficiency [see warnings and precautions (5.6)  and clinical pharmacology (12.3) ] . in patients who are known or suspected to be poor cyp2c9 metabolizers (i.e. cyp2c9*3/*3), based on genotype or previous history/experience with other cyp2c9 substrates (such as warfarin, phenytoin) administer celecoxib starting with half the lowest recommended dose. alternative management should be considered in jra patients identified to be cyp2c9 poor metabolizers [see dosage and administration (2.7) and clinical pharmacology (12.5)] .

미국 - 영어 - NLM (National Library of Medicine)

amneal pharmaceuticals of new york llc - felbamate (unii: x72rbb02n8) (felbamate - unii:x72rbb02n8) - felbamate tablets, usp are not indicated as a first line antiepileptic treatment (see warnings ). felbamate tablets, usp are recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. if these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgement, felbamate tablets, usp can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with lennox-gastaut syndrome in children. felbamate tablets are contraindicated in patients with known hypersensitivity to felbamate, its ingredients, or known sensitivity to other carbamates. it should not be used in patients with a history of any blood dyscrasia or hepatic dysfunction. abuse: abuse potential was not evaluated in human studies. dependence: rats administered felbamate orally at doses 8.3 times the recommended human dose 6 days each week for 5 consecutive weeks demonstrated no signs of physical dependence as measured by weight loss following drug withdrawal on day 7 of each week.

미국 - 영어 - NLM (National Library of Medicine)

amneal pharmaceuticals llc - diclofenac sodium (unii: qtg126297q) (diclofenac - unii:144o8ql0l1) - diclofenac sodium topical solution is indicated for the treatment of the pain of osteoarthritis of the knee(s). diclofenac sodium topical solution is contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [see warnings and precautions (5.7, 5.9)] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [see warnings and precautions (5.7, 5.8)] - in the setting of coronary artery bypass graft (cabg) surgery [see warnings and precautions (5.1)] risk summary use of nsaids, including diclofenac sodium topical solution, 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 diclofenac sodium topical solution use between about 20 and 30 weeks of gestation, and avoid diclofenac sodium topical solution 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 diclofenac sodium topical solution, 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, no evidence of malformations were observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses up to approximately 0.6, 0.6, and 1.3 times, respectively, the maximum recommended human dose (mrhd) of 162 mg diclofenac sodium via diclofenac sodium topical solution, despite the presence of maternal and fetal toxicity at these doses [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 diclofenac, 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. fetal/neonatal adverse reactions premature closure of the fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including diclofenac sodium topical solution, 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 diclofenac sodium topical solution treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue diclofenac sodium topical solution and follow up according to clinical practice (see data) . labor or delivery there are no studies on the effects of diclofenac sodium topical solution during labor or delivery. in animal studies, nsaids, including diclofenac inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. human data 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 post-marketing 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 post-marketing 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 reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce malformations despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.6 times the maximum recommended human dose [mrhd] of diclofenac sodium topical solution, 162 mg diclofenac sodium/day, based on body surface area (bsa) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.6 and 1.3-times, respectively, the mrhd based on bsa comparison). published reproductive and developmental studies of dimethyl sulfoxide (dmso, the solvent used in diclofenac sodium topical solution) are equivocal as to potential teratogenicity. in a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (0.12 and 0.24 times the mrhd, respectively, based on bsa comparison) from gestation day 15 through lactation day 21, significant maternal toxicity (peritonitis, mortality) was noted. these maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. diclofenac has been shown to cross the placental barrier in mice and rats. in published studies, diclofenac administration to pregnant rats prolonged gestation and produced liver toxicity and neuronal loss in offspring (1 mg/kg, ip; 0.06 times the mrhd based on bsa comparison), impaired nephrogenesis in the kidney (3.6 mg/kg, ip; 0.2 times the mrhd based on bsa comparison), and caused adverse effects on the developing testes (6.1 mg/kg, oral; 0.4 times the mrhd based on bsa comparison). risk summary based on available data, diclofenac may be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for diclofenac potassium tablets and any potential adverse effects on the breastfed infant from the diclofenac potassium tablets or from the underlying maternal condition. data one woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 mcg/l, equivalent to an infant dose of about 0.03 mg/kg/day. diclofenac was not detectable in breast milk in 12 women using diclofenac (after either 100 mg/day orally for 7 days or a single 50 mg intramuscular dose administered in the immediate postpartum period). infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including diclofenac sodium topical solution, 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 diclofenac sodium topical solution, in women who have difficulties conceiving or who are undergoing investigation of infertility. males published studies in adult male rodents report that diclofenac, at clinically relevant doses, can produce adverse effects on male reproductive tissues. the impact of these findings on male fertility is not clear [see nonclinical toxicology (13.1)] . safety and effectiveness in pediatric patients have not been established. 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)] . of the 911 patients treated with diclofenac sodium topical solution 1.5% in seven controlled, phase 3 clinical trials, 444 subjects were 65 years of age and over. there was no age-related difference in the incidence of adverse events. of the 793 patients treated with diclofenac sodium topical solution 1.5% in one open-labeled safety trial, 334 subjects were 65 years of age and over including 107 subjects 75 and over. there was no difference in the incidence of adverse events with long-term exposure to diclofenac sodium topical solution 1.5% for this elderly population. diclofenac (dye kloe’ fen ak) sodium topical solution, usp 2% w/w   read the medication guide that comes with diclofenac sodium first. be sure that you read, understand and follow these instructions for use before you use diclofenac sodium for the first time. important: for use on the skin only (topical). do not get diclofenac sodium in your eyes, nose or mouth. before you use diclofenac sodium: - apply diclofenac sodium exactly as your healthcare provider tells you. talk with your healthcare provider or pharmacist if you are not sure. - only use diclofenac sodium to treat pain from osteoarthritis in your knee or knees. - apply diclofenac sodium on clean, dry skin that does not have any cuts, infections or rashes. - use diclofenac sodium two times a day on your knee or knees as prescribed. - if you get diclofenac sodium in your eyes, rinse your eyes right away with water or saline. call your healthcare provider if your eyes are irritated for more than one hour. diclofenac sodium comes in a pump bottle. if you are using a diclofenac sodium pump bottle follow the steps below: before you use diclofenac sodium pump bottle for the first time, you will need to prime the pump. to prime the pump, remove the cap (see figure a ) and fully press the top of the pump all the way down 4 times while holding the bottle in an upright position (see figure b ). dispense this portion of the medicine into a tissue or paper towel and throw it away in a trash can. the pump is now ready to use. you should not need to prime the pump again. figure a.   figure b.   steps for using diclofenac sodium pump bottle: step 1:       wash your hands with soap and water before applying diclofenac sodium. step 2:       remove the bottle cap and press the pump head down firmly and fully to dispense diclofenac sodium into the palm of your hand. release the pump head and then press the pump head down firmly and fully a second time. when you use your diclofenac sodium pump bottle, you can hold the bottle at an angle. put 2 pumps of diclofenac sodium on your hand (see figure c ).   figure c. step 3:       apply diclofenac sodium evenly around the front, back, and sides of your knee. diclofenac sodium should be applied without massaging the knee (see figures d and e ).   figure d.   figure e. step 4:       repeat steps 2 and 3 for your other knee if your healthcare provider has prescribed diclofenac sodium for both knees. step 5:       wash your hands with soap and water right away after applying diclofenac sodium. step 6:       replace the cap on the bottle and store in an upright position. after you use diclofenac sodium: do not: - cover your knee with clothing until your knee is completely dry. - put sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medicines on your knee until it is completely dry. - take a shower or a bath for at least 30 minutes after you put diclofenac sodium on your knee(s). - use heating pads or cover the treated area with bandages where you have applied diclofenac sodium. - exercise following application of diclofenac sodium. - use sunlamp and tanning beds. protect your treated knee from sunlight. wear clothes that cover your skin if you have to be in the sunlight. how should i store diclofenac sodium? - store diclofenac sodium at room temperature between 68°f to 77°f (20°c to 25°c). keep diclofenac sodium and all medicines out of the reach of children. this instructions for use has been approved by the u.s. food and drug administration. distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 08-2022-01

오스트레일리아 - 영어 - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - irbesartan -

오스트레일리아 - 영어 - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - irbesartan -

오스트레일리아 - 영어 - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - irbesartan -