أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - hydrochlorothiazide,irbesartan -

أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - hydrochlorothiazide,irbesartan -

أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - rosuvastatin calcium -

أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - rosuvastatin calcium -

أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

amneal pharma australia pty ltd - rosuvastatin calcium -

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

amneal pharmaceuticals ny llc - chlordiazepoxide hydrochloride (unii: mfm6k1xwdk) (chlordiazepoxide - unii:6rz6xez3cr), clidinium bromide (unii: 91zqw5jf1z) (clidinium - unii:bo76jf850n) - chlordiazepoxide hydrochloride and clidinium bromide capsules are indicated to control emotional and somatic factors in gastrointestinal disorders. chlordiazepoxide hydrochloride and clidinium bromide capsules may also be used as adjunctive therapy in the treatment of peptic ulcer and in the treatment of the irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and acute enterocolitis. chlordiazepoxide hydrochloride and clidinium bromide capsules are contraindicated in the presence of glaucoma (since the anticholinergic component may produce some degree of mydriasis) and in patients with prostatic hypertrophy and benign bladder neck obstruction. it is contraindicated in patients with known hypersensitivity to chlordiazepoxide hydrochloride and/or clidinium bromide. chlordiazepoxide hydrochloride and clidinium bromide capsules contain chlordiazepoxide hydrochloride, a schedule iv controlled substance and clidinium bromide, which is not a controlled substance. chlordiazepoxide hydrochloride and clidinium bromide capsules are exempted from schedule iv and is not controlled under the controlled substances act. chlordiazepoxide hydrochloride, a component of chlordiazepoxide hydrochloride and clidinium bromide capsules, is a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings ). the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). physical dependence chlordiazepoxide hydrochloride and clidinium bromide capsules may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use (see warnings ). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride and clidinium bromide capsules or reduce the dosage (see warnings and dosage and administration ). acute withdrawal signs and symptoms acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures and suicidality. protracted withdrawal syndrome protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance to chlordiazepoxide hydrochloride and clidinium bromide capsules may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effects of chlordiazepoxide hydrochloride and clidinium bromide capsules may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

الولايات المتحدة - الإنجليزية - 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)] .

الولايات المتحدة - الإنجليزية - 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)] .

الولايات المتحدة - الإنجليزية - 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.

أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

gilead sciences pty ltd - emtricitabine; efavirenz; tenofovir disoproxil fumarate -