New Zealand - Inggeris - Medsafe (Medicines Safety Authority)

upjohn new zealand ulc - atorvastatin calcium 10.85mg equivalent to 10 mg atorvastatin;   - film coated tablet - 10 mg - active: atorvastatin calcium 10.85mg equivalent to 10 mg atorvastatin   excipient: calcium carbonate croscarmellose sodium hyprolose lactose monohydrate magnesium stearate microcrystalline cellulose opadry white ys-1-7040 polysorbate 80 simeticone - atorvastatin pfizer is indicated as an adjunct to diet to reduce elevated total-c, ldl-c and tg levels in patients with primary hypercholesterolaemia or mixed dyslipidaemia where the primary abnormality is either elevated cholesterol or triglycerides when response to diet and other non-pharmacological measures is inadequate. atorvastatin pfizer is also indicated to reduce total-c and ldl-c in patients with heterozygous and homozygous familial hypercholesterolaemia.

New Zealand - Inggeris - Medsafe (Medicines Safety Authority)

upjohn new zealand ulc - atorvastatin calcium 21.7mg equivalent to 20 mg atorvastatin;   - film coated tablet - 20 mg - active: atorvastatin calcium 21.7mg equivalent to 20 mg atorvastatin   excipient: calcium carbonate croscarmellose sodium hyprolose lactose monohydrate magnesium stearate microcrystalline cellulose opadry white ys-1-7040 polysorbate 80 simeticone - atorvastatin pfizer is indicated as an adjunct to diet to reduce elevated total-c, ldl-c and tg levels in patients with primary hypercholesterolaemia or mixed dyslipidaemia where the primary abnormality is either elevated cholesterol or triglycerides when response to diet and other non-pharmacological measures is inadequate. atorvastatin pfizer is also indicated to reduce total-c and ldl-c in patients with heterozygous and homozygous familial hypercholesterolaemia.

New Zealand - Inggeris - Medsafe (Medicines Safety Authority)

upjohn new zealand ulc - atorvastatin calcium 43.4mg equivalent to 40 mg atorvastatin;   - film coated tablet - 40 mg - active: atorvastatin calcium 43.4mg equivalent to 40 mg atorvastatin   excipient: calcium carbonate croscarmellose sodium hyprolose lactose monohydrate magnesium stearate microcrystalline cellulose opadry white ys-1-7040 polysorbate 80 simeticone - atorvastatin pfizer is indicated as an adjunct to diet to reduce elevated total-c, ldl-c and tg levels in patients with primary hypercholesterolaemia or mixed dyslipidaemia where the primary abnormality is either elevated cholesterol or triglycerides when response to diet and other non-pharmacological measures is inadequate. atorvastatin pfizer is also indicated to reduce total-c and ldl-c in patients with heterozygous and homozygous familial hypercholesterolaemia.

New Zealand - Inggeris - Medsafe (Medicines Safety Authority)

upjohn new zealand ulc - atorvastatin calcium 86.8mg equivalent to 80 mg atorvastatin;   - film coated tablet - 80 mg - active: atorvastatin calcium 86.8mg equivalent to 80 mg atorvastatin   excipient: calcium carbonate croscarmellose sodium hyprolose lactose monohydrate magnesium stearate microcrystalline cellulose opadry white ys-1-7040 polysorbate 80 simeticone - atorvastatin pfizer is indicated as an adjunct to diet to reduce elevated total-c, ldl-c and tg levels in patients with primary hypercholesterolaemia or mixed dyslipidaemia where the primary abnormality is either elevated cholesterol or triglycerides when response to diet and other non-pharmacological measures is inadequate. atorvastatin pfizer is also indicated to reduce total-c and ldl-c in patients with heterozygous and homozygous familial hypercholesterolaemia.

Singapura - Inggeris - HSA (Health Sciences Authority)

pfizer private limited - daptomycin - injection, powder, lyophilized, for solution - daptomycin 500mg/vial

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

pfizer laboratories div pfizer inc - morphine sulfate (unii: x3p646a2j0) (morphine - unii:76i7g6d29c), naltrexone hydrochloride (unii: z6375yw9sf) (naltrexone - unii:5s6w795cqm) - morphine sulfate 20 mg - embeda is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see warnings and precautions (5.1)] , reserve embeda for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - embeda is not indicated as an as-needed (prn) analgesic. embeda is contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.3)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.6)] - con

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

pfizer laboratories div pfizer inc - epoetin (unii: 64fs3bfh5w) (erythropoietin - unii:64fs3bfh5w) - retacrit is indicated for the treatment of anemia due to chronic kidney disease (ckd), including patients on dialysis and not on dialysis to decrease the need for red blood cell (rbc) transfusion. retacrit is indicated for the treatment of anemia due to zidovudine administered at ≤ 4,200 mg/week in patients with hiv-infection with endogenous serum erythropoietin levels of ≤ 500 munits/ml. retacrit is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. retacrit is indicated to reduce the need for allogeneic rbc transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dl who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. retacrit is not indicated for patients who are willing to donate autologous blood pre-operatively. retacrit has not been shown to improv

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

pfizer laboratories div pfizer inc - rituximab (unii: 4f4x42syq6) (rituximab - unii:4f4x42syq6) - ruxience is indicated for the treatment of adult patients with: ruxience, in combination with fludarabine and cyclophosphamide (fc), is indicated for the treatment of adult patients with previously untreated and previously treated cd20-positive cll. ruxience, in combination with methotrexate, is indicated for the treatment of adult patients with moderately-to severely-active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (tnf) antagonist therapies. ruxience, in combination with glucocorticoids, is indicated for the treatment of adult patients with granulomatosis with polyangiitis (gpa) (wegener's granulomatosis) and microscopic polyangiitis (mpa). none. risk summary based on human data, rituximab products can cause adverse developmental outcomes including b-cell lymphocytopenia in infants exposed in-utero (see clinical considerations) . in animal reproduction studies, intravenous administration of rituximab to pregnant cynomolgus monkeys during the period of organogenesis caused lymphoid b-cell depletion in the newborn offspring at doses resulting in 80% of the exposure (based on auc) of those achieved following a dose of 2 grams in humans. advise pregnant women of the risk to a fetus. adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. the background risk of major birth defects and miscarriage for the indicated populations is unknown. the estimated background risk in the u.s. general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies. clinical considerations fetal/neonatal adverse reactions observe newborns and infants for signs of infection and manage accordingly. data human data postmarketing data indicate that b-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. rituximab was detected postnatally in the serum of infants exposed in-utero. animal data an embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. pregnant animals received rituximab via the intravenous route during early gestation (organogenesis period; post coitum days 20 through 50). rituximab was administered as loading doses on post coitum (pc) days 20, 21, and 22, at 15, 37.5, or 75 mg/kg/day, and then weekly on pc days 29, 36, 43, and 50, at 20, 50, or 100 mg/kg/week. the 100 mg/kg/week dose resulted in 80% of the exposure (based on auc) of those achieved following a dose of 2 grams in humans. rituximab crosses the monkey placenta. exposed offspring did not exhibit any teratogenic effects but did have decreased lymphoid tissue b cells. a subsequent pre- and postnatal reproductive toxicity study in cynomolgus monkeys was completed to assess developmental effects including the recovery of b cells and immune function in infants exposed to rituximab in-utero. animals were treated with a loading dose of 0, 15, or 75 mg/kg every day for 3 days, followed by weekly dosing with 0, 20, or 100 mg/kg dose. subsets of pregnant females were treated from pc day 20 through postpartum day 78, pc day 76 through pc day 134, and from pc day 132 through delivery and postpartum day 28. regardless of the timing of treatment, decreased b cells and immunosuppression were noted in the offspring of rituximab-treated pregnant animals. the b-cell counts returned to normal levels, and immunologic function was restored within 6 months postpartum. there are limited data on the presence of rituximab in human milk, and the effect on the breastfed child, and there are no data on the effect on milk production. rituximab is detected in the milk of lactating cynomolgus monkeys, and maternal igg is present in human breast milk. rituximab has also been reported to be excreted at low concentrations in human breast milk. given that the clinical significance of this finding for children is not known, advise women not to breastfeed during treatment with ruxience and for 6 months after the last dose due to the potential of serious adverse reactions in breastfed children. rituximab products can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy testing verify pregnancy status in females of reproductive potential prior to initiating ruxience. contraception females advise females of reproductive potential to use effective contraception during treatment with ruxience and for 12 months after the last dose. the safety and effectiveness of ruxience have not been established in pediatric patients with nhl, cll or ra. rituximab was not studied in pediatric patients with polyarticular juvenile idiopathic arthritis (pjia) due to concerns regarding the potential for prolonged immunosuppression as a result of b-cell depletion in the developing juvenile immune system. diffuse large b-cell nhl among patients with dlbcl evaluated in three randomized, active-controlled trials, 927 patients received rituximab in combination with chemotherapy. of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. no overall differences in effectiveness were observed between these patients and younger patients. cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients. serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis. low-grade or follicular non-hodgkin's lymphoma patients with previously untreated follicular nhl evaluated in nhl study 5 were randomized to rituximab as single-agent maintenance therapy (n=505) or observation (n=513) after achieving a response to rituximab in combination with chemotherapy. of these, 123 (24%) patients in the rituximab arm were age 65 or older. no overall differences in safety or effectiveness were observed between these patients and younger patients. other clinical studies of rituximab in low-grade or follicular, cd20-positive, b-cell nhl did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. chronic lymphocytic leukemia among patients with cll evaluated in two randomized active-controlled trials, 243 of 676 rituximab-treated patients (36%) were 65 years of age or older; of these, 100 rituximab-treated patients (15%) were 70 years of age or older. in exploratory analyses defined by age, there was no observed benefit from the addition of rituximab to fludarabine and cyclophosphamide among patients 70 years of age or older in cll study 1 or in cll study 2; there was also no observed benefit from the addition of rituximab to fludarabine and cyclophosphamide among patients 65 years of age or older in cll study 2 [see clinical studies (14.5)] . patients 70 years or older received lower dose intensity of fludarabine and cyclophosphamide compared to younger patients, regardless of the addition of rituximab. in cll study 1, the dose intensity of rituximab was similar in older and younger patients, however in cll study 2 older patients received a lower dose intensity of rituximab. the incidence of grade 3 and 4 adverse reactions was higher among patients receiving r-fc who were 70 years or older compared to younger patients for neutropenia [44% vs. 31% (cll study 1); 56% vs. 39% (cll study 2)], febrile neutropenia [16% vs. 6% (nhl study 10 (nct00719472))], anemia [5% vs. 2% (cll study 1); 21% vs. 10% (cll study 2)], thrombocytopenia [19% vs. 8% (cll study 2)], pancytopenia [7% vs. 2% (cll study 1); 7% vs. 2% (cll study 2)], and infections [30% vs. 14% (cll study 2)]. rheumatoid arthritis among the 2,578 patients in global ra studies completed to date, 12% were 65–75 years old and 2% were 75 years old and older. the incidences of adverse reactions were similar between older and younger patients. the rates of serious adverse reactions, including serious infections, malignancies, and cardiovascular events were higher in older patients. granulomatosis with polyangiitis (gpa) (wegener's granulomatosis) and microscopic polyangiitis of the 99 rituximab-treated gpa and mpa patients in gpa/mpa study 1, 36 (36%) were 65 years old and over, while 8 (8%) were 75 years and over. no overall differences in efficacy were observed between patients that were 65 years old and over and younger patients. the overall incidence and rate of all serious adverse events was higher in patients 65 years old and over. the clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. in gpa/mpa study 2, 30 (26%) of the enrolled patients were at least 65 years old, of which 12 patients were exposed to non-u.s.-licensed rituximab and 18 were exposed to azathioprine. the clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

Amerika Syarikat - Inggeris - 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)] .

Amerika Syarikat - Inggeris - 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) ].