Canada - Tiếng Anh - Health Canada

pfizer consumer healthcare a division of pfizer canada ulc - ibuprofen (ibuprofen sodium dihydrate) - tablet - 200mg - ibuprofen (ibuprofen sodium dihydrate) 200mg - other nonsteroidal antiimflammatory agents

Canada - Tiếng Anh - Health Canada

pfizer consumer healthcare a division of pfizer canada ulc - ibuprofen (ibuprofen sodium dihydrate) - tablet - 200mg - ibuprofen (ibuprofen sodium dihydrate) 200mg - other nonsteroidal antiimflammatory agents

Canada - Tiếng Anh - Health Canada

pfizer consumer healthcare a division of pfizer canada ulc - ibuprofen (ibuprofen sodium dihydrate) - tablet - 400mg - ibuprofen (ibuprofen sodium dihydrate) 400mg - other nonsteroidal antiimflammatory agents

Hoa Kỳ - Tiếng Anh - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - infliximab (unii: b72hh48flu) (infliximab - unii:b72hh48flu) - infliximab, license holder unspecified 100 mg in 10 ml - inflectra is indicated for: inflectra is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active cd who have had an inadequate response to conventional therapy. inflectra is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis (uc) who have had an inadequate response to conventional therapy. inflectra is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active uc who have had an inadequate response to conventional therapy. inflectra, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (ra). inflectra is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis (as). inflectra is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in adult patients with psoriatic arthritis (psa). inflectra is indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis (ps) who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. inflectra should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see boxed warning, warnings and precautions (5)] . the use of inflectra at doses >5 mg/kg is contraindicated in patients with moderate or severe heart failure [see warnings and precautions (5.5) and adverse reactions (6.1)]. inflectra is contraindicated in patients with a previous severe hypersensitivity reaction to infliximab products or any of the inactive ingredients of inflectra or any murine proteins [severe hypersensitivity reactions have included anaphylaxis, hypotension, and serum sickness] [see warnings and precautions (5.7) and adverse reactions (6.1)]. risk summary available observational studies in pregnant women exposed to infliximab products showed no increased risk of major malformations among live births as compared to those exposed to non-biologics. however, findings on other birth and maternal outcomes were not consistent across studies of different study design and conduct (see data) . monoclonal antibodies such as infliximab products are transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant (see clinical considerations). because infliximab products do not cross-react with tnfα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with infliximab products. in a developmental study conducted in mice using an analogous antibody, no evidence of maternal toxicity or fetal harm was observed (see data) . all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease or rheumatoid arthritis associated with increased disease activity. adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5 kg) and small for gestational age at birth. fetal/neonatal adverse reactions as with other igg antibodies, infliximab products cross the placenta. infliximab products have been detected in the serum of infants up to 6 months following birth. consequently, these infants may be at increased risk of infection, including disseminated infection which can become fatal. at least a six month waiting period following birth is recommended before the administration of live vaccines (e.g., bcg vaccine or other live vaccines, such as the rotavirus vaccine) to these infants [see warnings and precautions (5.13)] . cases of agranulocytosis in infants exposed in utero have also been reported [see adverse reactions (6.3)] . data human data two prospective cohort studies were conducted assessing birth outcomes as well as the health status of infants up to the age of one year in women exposed to infliximab compared to non-biologic comparators including methotrexate, azathioprine, 6-mercaptopurine and systemic corticosteroids used for the treatment of similar diseases. the first study was conducted in an ibd pregnancy registry in the united states and assessed pregnancy outcomes in 294 women with inflammatory bowel disease exposed to infliximab during pregnancy compared with 515 women on a non-biologic treatment. infliximab exposure was not associated with increased rates of major congenital malformations, miscarriage/stillbirth, infants of low birth weight, small for gestational age, or infection in the first year of life. the second study among ibd and non-ibd patients in sweden, finland, and denmark compared 97, 7, and 166 women exposed to infliximab to 2,693, 2,499 and 1,268 women on non-biologic systemic therapy, respectively. in this study, comparing pooled data across the three countries, exposure to infliximab was not associated with increased rates of congenital anomalies or infant death. infliximab in combination with immunosuppressants (mainly systemic corticosteroids and azathioprine) was associated with increased rates of preterm birth, small for gestational age, low birth weight, and infant hospitalization for infection compared with non-biologic systemic treatment. although the study did not show any associations with infliximab monotherapy, the analyses could have been underpowered to detect an association. there were additional methodological limitations with these studies that may account for the study findings in both studies: the concomitant use of other medications or treatments was not controlled and disease severity was not assessed; in the u.s. study, patient reported outcomes were collected without clinical validation. these methodological limitations hinder interpretation of the study results. animal data because infliximab products do not cross-react with tnfα in species other than humans and chimpanzees, animal reproduction studies have not been conducted with infliximab products. an embryofetal development study was conducted in pregnant mice using cv1q anti-mouse tnfα, an analogous antibody that selectively inhibits the functional activity of mouse tnfα. this antibody administered in mice, during the period of organogenesis on gestation days (gds) 6 and 12, at iv doses up to 40 mg/kg produced no evidence of maternal toxicity, fetal mortality, or structural abnormalities. doses of 10 to 15 mg/kg in pharmacodynamic animal models with the anti-tnf analogous antibody produced maximal pharmacologic effectiveness. analyses of fetal samples on gd 14 indicated placental transfer of the antibody and exposure of the fetuses during organogenesis. in a peri-and post-natal development study in mice, no maternal toxicity or adverse developmental effects in offspring were observed when dams were administered iv doses of 10 or 40 mg/kg of the analogous antibody on gds 6, 12 and 18 and lactation days 3, 9 and 15. risk summary published literature show that infliximab is present at low levels in human milk. systemic exposure in a breastfed infant is expected to be low because infliximab products are largely degraded in the gastrointestinal tract. a u.s. multi-center study of 168 women treated with infliximab for inflammatory bowel disease (breast milk samples obtained, n=29) showed that infants exposed to infliximab through breast milk had no increase in rates of infections and developed normally. there are no data on the effects of infliximab products on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for inflectra and any potential adverse effects on the breastfed child from inflectra or from the underlying maternal condition. the safety and effectiveness of infliximab products have been established in pediatric patients 6 to 17 years of age for induction and maintenance treatment of cd and uc. [see dosage and administration (2.2, 2.4) and adverse reactions (6.1)] . however, the safety and effectiveness of infliximab products in pediatric patients <6 years of age with cd or uc have not been established. the safety and effectiveness of infliximab products in the treatment of pediatric patients with ps and juvenile rheumatoid arthritis (jra) have not been established. pediatric crohn's disease the safety and effectiveness of infliximab products have been established for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active cd who have had an inadequate response to conventional therapy. the use of infliximab for this indication is supported by evidence from a randomized, open-label pediatric cd study in 112 pediatric patients aged 6 years and older [see clinical studies (14.2)] . infliximab has been studied only in combination with conventional immunosuppressive therapy in pediatric cd. the longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric cd patients have not been established in clinical trials. postmarketing cases of hstcl have been reported in pediatric patients treated with tnf blockers including infliximab products. due to the risk of hstcl, a careful risk-benefit assessment should be made when inflectra is used in combination with other immunosuppressants in pediatric cd patients [see boxed warning, warnings and precautions (5.2)] . pediatric ulcerative colitis the safety and effectiveness of infliximab products for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active uc who have had an inadequate response to conventional therapy have been established. the use of infliximab for this indication is supported by evidence from adequate and well-controlled studies of infliximab in adults with additional safety and pharmacokinetic data from an open-label pediatric uc study in 60 pediatric patients aged 6 years and older [see dosage and administration (2.4), adverse reactions (6.1), and clinical studies (14.4)] . the effectiveness of infliximab in inducing and maintaining mucosal healing in pediatric uc was not established. although 41 patients had a mayo endoscopy subscore of 0 or 1 at the week 8 endoscopy, the induction phase was open-label and lacked a control group. only 9 patients had an optional endoscopy at week 54. approximately half of the patients were on concomitant immunomodulators (aza, 6-mp, mtx) at study start. due to the risk of hstcl, a careful risk-benefit assessment should be made when inflectra is used in combination with other immunosuppressants in pediatric uc patients [see boxed warning and warnings and precautions (5.2)]. the longer term (greater than 1 year) safety and effectiveness of infliximab products in pediatric uc patients have not been established in clinical trials. juvenile rheumatoid arthritis (jra) the safety and effectiveness of infliximab products in the treatment of pediatric patients with juvenile rheumatoid arthritis (jra) have not been established. the safety and efficacy of infliximab in patients with jra were evaluated in a multicenter, randomized, placebo-controlled, double-blind study for 14 weeks, followed by a double-blind, all-active treatment extension, for a maximum of 44 weeks. patients with active jra between the ages of 4 and 17 years who had been treated with mtx for at least 3 months were enrolled. concurrent use of folic acid, oral corticosteroids (≤0.2 mg/kg/day of prednisone or equivalent), nsaids, and/or disease modifying antirheumatic drugs (dmards) was permitted. doses of 3 mg/kg of infliximab or placebo were administered intravenously at weeks 0, 2 and 6. patients randomized to placebo crossed-over to receive 6 mg/kg of infliximab at weeks 14, 16, and 20, and then every 8 weeks through week 44. patients who completed the study continued to receive open-label treatment with infliximab for up to 2 years in a companion extension study. the study failed to establish the efficacy of infliximab in the treatment of jra. key observations in the study included a high placebo response rate and a higher rate of immunogenicity than what has been observed in adults. additionally, a higher rate of clearance of infliximab was observed than had been observed in adults. population pharmacokinetic analysis showed that in pediatric patients with jra with a body weight of up to 35 kg receiving 6 mg/kg infliximab and pediatric patients with jra with body weight greater than 35 kg up to adult body weight receiving 3 mg/kg infliximab, the steady state area under the concentration curve (aucss) was similar to that observed in adults receiving 3 mg/kg of infliximab. a total of 60 patients with jra were treated with doses of 3 mg/kg and 57 patients were treated with doses of 6 mg/kg. the proportion of patients with infusion reactions who received 3 mg/kg infliximab was 35% (21/60) over 52 weeks compared with 18% (10/57) in patients who received 6 mg/kg over 38 weeks. the most common infusion reactions reported were vomiting, fever, headache, and hypotension. in the 3 mg/kg infliximab group, 4 patients had a serious infusion reaction and 3 patients reported a possible anaphylactic reaction (2 of which were among the serious infusion reactions). in the 6 mg/kg infliximab group, 2 patients had a serious infusion reaction, 1 of whom had a possible anaphylactic reaction. two of the 6 patients who experienced serious infusion reactions received infliximab by rapid infusion (duration of less than 2 hours). antibodies to infliximab developed in 38% (20/53) of patients who received 3 mg/kg infliximab compared with 12% (6/49) of patients who received 6 mg/kg. a total of 68% (41/60) of patients who received 3 mg/kg of infliximab in combination with mtx experienced an infection over 52 weeks compared with 65% (37/57) of patients who received 6 mg/kg of infliximab in combination with mtx over 38 weeks. the most commonly reported infections were upper respiratory tract infection and pharyngitis, and the most commonly reported serious infection was pneumonia. other notable infections included primary varicella infection in 1 patient and herpes zoster in 1 patient. of the total number of infliximab-treated patients in ra and ps clinical studies, 256 (9.6%) were 65 years old and over, while 17 (0.6%) were 75 years old and over. in these trials, no overall differences in safety or effectiveness were observed between geriatric patients (patients ≥65 years old) and younger adult patients (patients 18 to 65 years old). however, the incidence of serious adverse reactions in geriatric patients was higher in both infliximab and control groups compared to younger adult patients. of the total number of infliximab-treated patients in cd, uc, as, and psa clinical studies, 76 (3.2%) were 65 years old and over, while 9 (0.4%) were 75 years old and over. in the cd, uc, as, and psa studies, there were insufficient numbers of geriatric patients to determine whether they respond differently from younger adults. the incidence of serious infections in infliximab-treated geriatric patients was greater than in infliximab-treated younger adult patients; therefore close monitoring of geriatric patients for the development of serious infections is recommended [see warnings and precautions (5.1), and adverse reactions (6.1)] .

Hoa Kỳ - Tiếng Anh - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - celecoxib (unii: jcx84q7j1l) (celecoxib - unii:jcx84q7j1l) - celecoxib 50 mg - celebrex is indicated 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) ]. celebrex is contraindicated in the following patients: risk summary use of nsaids, including celebrex, 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 celebrex use between about 20 and 30 weeks of gestation and avoid celebrex use at about 30 weeks of gestation and later in pregnancy (see error! hyperlink reference not valid. , error! hyperlink reference not valid. ). premature closure of fetal ductus arteriosus use of nsaids, including celebrex, 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 error! hyperlink reference not valid. ). 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 celebrex, can cause premature closure of the fetal ductus arteriosus (see error! hyperlink reference not valid. ). 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 celebrex treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue celebrex and follow up according to clinical practice (see error! hyperlink reference not valid. ). labor or delivery there are no studies on the effects of celebrex 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 celebrex. premature closure of fetal ductus arteriosus: published literature reports that the use of nsaids at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment: published studies and postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data 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 celebrex 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 celebrex 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 celebrex is administered to a nursing woman. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for celebrex and any potential adverse effects on the breastfed infant from the celebrex or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including celebrex, 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 celebrex, in women who have difficulties conceiving or who are undergoing investigation of infertility. celebrex 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 celebrex has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to celebrex 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 celebrex in pre-approval clinical trials, more than 3,300 were 65–74 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 celebrex capsules in patients with moderate hepatic impairment (child-pugh class b) should be reduced by 50%. the use of celebrex in patients with severe hepatic impairment is not recommended [see dosage and administration (2.7) and clinical pharmacology (12.3) ]. celebrex 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 celebrex 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) ].

Hoa Kỳ - Tiếng Anh - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - piroxicam (unii: 13t4o6vmam) (piroxicam - unii:13t4o6vmam) - piroxicam 10 mg - feldene is indicated: feldene is contraindicated in the following patients: risk summary use of nsaids, including feldene, 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 feldene use between about 20 and 30 weeks of gestation, and avoid feldene 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 feldene, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. oligohydramnios/neonatal renal impairment use of nsaids at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. data from observational studies regarding other potential embryofetal risks of nsaid use in women in the first or second trimesters of pregnancy are inconclusive. in animal reproduction studies in rats and rabbits, there was no evidence of teratogenicity at exposures up to 5 and 10 times the maximum recommended human dose (mrhd), respectively. in rat studies with piroxicam, fetotoxicity (postimplantation loss) was observed at exposures 2 times the mrhd, and delayed parturition and an increased incidence of stillbirth were noted at doses equivalent to the mrhd of piroxicam. 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 piroxicam, resulted in increased pre- and post-implantation loss. prostaglandins also have been shown to have an important role in fetal kidney development. in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions premature closure of fetal ductus arteriosus: avoid use of nsaids in women at about 30 weeks gestation and later in pregnancy, because nsaids, including feldene, 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 feldene treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. if oligohydramnios occurs, discontinue feldene and follow up according to clinical practice (see data ). labor or delivery there are no studies on the effects of feldene during labor or delivery. in animal studies, nsaids, including piroxicam inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. data 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 postmarketing reports describe maternal nsaid use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. in many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. there have been a limited number of case reports of maternal nsaid use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. these limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal nsaid use. because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to nsaids through maternal use is uncertain. animal data pregnant rats administered piroxicam at 2, 5, or 10 mg/kg/day during the period of organogenesis (gestation days 6 to 15) demonstrated increased post-implantation losses with 5 and 10 mg/kg/day of piroxicam (equivalent to 2 and 5 times the mrhd, of 20 mg respectively, based on a mg/m2 body surface area [bsa]). there were no drug-related developmental abnormalities noted in offspring. gastrointestinal tract toxicity was increased in pregnant rats in the last trimester of pregnancy compared to non-pregnant rats or rats in earlier trimesters of pregnancy. pregnant rabbits administered piroxicam at 2, 5, or 10 mg/kg/day during the period of organogenesis (gestation days 7 to 18) demonstrated no drug-related developmental abnormalities in offspring (up to 10 times the mrhd based on a mg/m2 bsa). in a pre- and post-natal development study in which pregnant rats were administered piroxicam at 2, 5, or 10 mg/kg/day on gestation day 15 through delivery and weaning of offspring, reduced weight gain and death were observed in dams at 10 mg/kg/day (5 times the mrhd based on a mg/m2 bsa) starting on gestation day 20. treated dams revealed peritonitis, adhesions, gastric bleeding, hemorrhagic enteritis and dead fetuses in utero. parturition was delayed and there was an increased incidence of stillbirth in all piroxicam-treated groups (at doses equivalent to the mrhd). postnatal development could not be reliably assessed due to the absence of maternal care secondary to severe maternal toxicity. risk summary limited data from 2 published reports that included a total of 6 breastfeeding women and 2 infants showed piroxicam is excreted in human milk at approximately 1% to 3% of the maternal concentration. no accumulation of piroxicam occurred in milk relative to that in maternal plasma during treatment. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for feldene and any potential adverse effects on the breastfed infant from the feldene or from the underlying maternal condition. infertility females based on the mechanism of action, the use of prostaglandin-mediated nsaids, including feldene, 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 feldene, in women who have difficulties conceiving or who are undergoing investigation of infertility. feldene has not been investigated in pediatric patients. the safety and effectiveness of feldene 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)] .

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

pfizer australia pty ltd - mitozantrone hydrochloride -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

pfizer australia pty ltd - mitozantrone hydrochloride -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

pfizer australia pty ltd - mitozantrone hydrochloride -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

pfizer australia pty ltd - midazolam, quantity: 1 mg/ml - injection, solution - excipient ingredients: hydrochloric acid; sodium hydroxide; sodium chloride; water for injections - intravenously as an agent for: conscious sedation prior to short surgical, diagnostic, therapeutic or endoscopic procedures such as bronchoscopy, gastroscopy, cystoscopy,coronary angiography and cardiac catheterisation, either alone or in conjunction with an opioid. induction of anaesthesia preliminary to administration of other anaesthetic agents. with the use of an opioid premedicant, induction of anaesthesia can be obtained with a narrower dose range and in a shorter period of time. intermittent intravenous administration or continuous infusion for: sedation in intensive care units. intramuscularly for: preoperative sedation (induction of sleepiness or drowsiness and relief of apprehension) and to impair memory of perioperative events.