Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - nafarelin acetate (unii: 8enz0qjw4h) (nafarelin - unii:1x0094v6jv) - nafarelin 2 mg in 1 ml - (for endometriosis, see reverse side ) synarel is indicated for treatment of central precocious puberty (cpp) (gonadotropin-dependent precocious puberty) in children of both sexes. the diagnosis of central precocious puberty (cpp) is suspected when premature development of secondary sexual characteristics occurs at or before the age of 8 years in girls and 9 years in boys, and is accompanied by significant advancement of bone age and/or a poor adult height prediction. the diagnosis should be confirmed by pubertal gonadal sex steroid levels and a pubertal lh response to stimulation by native gnrh. pelvic ultrasound assessment in girls usually reveals enlarged uterus and ovaries, the latter often with multiple cystic formations. magnetic resonance imaging or ct-scanning of the brain is recommended to detect hypothalamic or pituitary tumors, or anatomical changes associated with increased intracranial pressure. other causes of sexual precocity, such as congenital adrenal hyperplasia, testotoxicosis, testicular

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - glasdegib (unii: k673dmo5h9) (glasdegib - unii:k673dmo5h9) - daurismo is indicated, in combination with low-dose cytarabine, for the treatment of newly-diagnosed acute myeloid leukemia (aml) in adult patients who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy. none. risk summary based on its mechanism of action and findings in animal embryo-fetal developmental toxicity studies, daurismo can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no clinical data on the use of daurismo in pregnant women to inform of a drug-associated risk of major birth defects and miscarriage. daurismo is not recommended for use during pregnancy. conduct pregnancy testing in female patients of reproductive potential prior to initiating treatment with daurismo. report pregnancy exposures to pfizer at 1-800-438-1985. in animal embryo-fetal developmental toxicity studies, repeat-dose oral administration of daurismo during organogenesis at maternal exposures that were less than the human exposu

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - ritlecitinib tosylate (unii: eag4t1459k) (ritlecitinib - unii:2oye00pc25) - litfulo is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older. limitations of use : not recommended for use in combination with other jak inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants. litfulo is contraindicated in patients with known hypersensitivity to ritlecitinib or any of its excipients [see warnings and precautions (5.6)] .       if a patient becomes pregnant while receiving litfulo, healthcare providers should report litfulo exposure by calling 1-877-390-2940. risk summary available data from clinical trials with litfulo use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. in animal reproduction studies, oral administration of ritlecitinib to pregnant rats and rabbits during organogenesis caused fetotoxicity and fetal malformations at exposures 49 and 55 times the maximum recommended human dose (mrhd) based on area under the curve (auc) comparison, respectively (see animal data) . the background risks of major birth defects and miscarriage for the indicated population are unknown. all pregnancies carry some risk of birth defects, loss, or other adverse outcomes. the estimated background risks in the u.s. general population of major birth defects and miscarriages are 2-4% and 15-20% of clinically recognized pregnancies, respectively. data animal data in an embryo-fetal development study in pregnant rats, oral administration of ritlecitinib from gestation days 6 to 17 decreased fetal body weights and caused fetal skeletal malformations (malformed vertebrae and ribs) and variations (delayed ossification) at doses ≥175 mg/kg/day (49 times the mrhd based on auc comparison). maternal toxicity (lower body weights) was noted at 325 mg/kg/day (102 times the mrhd based on auc comparison). there was no developmental toxicity at 75 mg/kg/day (16 times the mrhd based on auc comparison). in an embryo-fetal development study in pregnant rabbits, oral administration of ritlecitinib from gestation days 7 to 19 decreased mean fetal body weights and increased visceral malformations (malpositioned kidneys), skeletal malformations (supernumerary sternebrae, absent thoracic arch, and/or fused thoracic centra), and skeletal variations (delayed ossification) at 75 mg/kg/day (55 times the mrhd based on auc comparison). there was no developmental toxicity at doses up to 25 mg/kg/day (12 times the mrhd based on auc comparison). in a pre- and postnatal development study in rats, oral administration of ritlecitinib from gestation day 6 through lactation day 20 had no effects on pre- and postnatal development at doses up to 75 mg/kg/day (14 times the mrhd based on auc comparison). at 175 mg/kg/day (41 times the mrhd based on auc comparison), ritlecitinib caused adverse lower postnatal survival and lower offspring body weights, which correlated with delayed sexual maturation in both sexes. bred females in the f1 generation also exhibited lower mean numbers of corpora lutea at 175 mg/kg/day. risk summary there are no data on the presence of ritlecitinib in human milk, the effects on the breastfed infant, or the effects on milk production. ritlecitinib is present in the milk of lactating rats (see data) . when a drug is present in animal milk, it is likely that it will be present in human milk. because of the serious adverse effects in adults, including risks of serious infection and malignancy, advise women not to breastfeed during treatment with litfulo and for approximately 14 hours after the last dose (approximately 6 elimination half-lives). data after a single oral 30 mg/kg dose of ritlecitinib to lactating rats, ritlecitinib concentrations in milk over time were higher than those in plasma. the mean milk to plasma auc ratio was 2.2. the safety and effectiveness of litfulo for the treatment of alopecia areata have been established in pediatric patients ages 12 years and older. a total of 181 pediatric patients ages 12 to <18 years were enrolled in alopecia areata clinical trials, with 105 pediatric patients ages 12 to <18 years with alopecia areata randomized in a pivotal, double-blind, placebo-controlled trial (trial aa-i). efficacy was consistent between the pediatric patients and adults [see clinical studies (14)] . the adverse reaction profile in the pediatric patients was similar to adults. the safety and efficacy of litfulo have not been established in pediatric patients under 12 years of age. no dose adjustment is required for patients ≥65 years of age. a total of 28 patients enrolled in alopecia areata trials were 65 years of age and older, and none were 75 years of age and older. clinical trials of litfulo did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients. as there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly. no dose adjustment is required in patients with mild (child pugh a) or moderate (child pugh b) hepatic impairment. litfulo is not recommended in patients with severe (child pugh c) hepatic impairment [see dosage and administration (2.3) and clinical pharmacology (12.3)] .

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - varenicline tartrate (unii: 82269asb48) (varenicline - unii:w6hs99o8zo) - varenicline 0.5 mg - chantix is indicated for use as an aid to smoking cessation treatment. chantix is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to chantix.             risk summary available data have not suggested an increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke [see data]. smoking during pregnancy is associated with maternal, fetal, and neonatal risks (see clinical considerations) . in animal studies, varenicline did not result in major malformations but caused decreased fetal weights in rabbits when dosed during organogenesis at exposures equivalent to 50 times the exposure at the maximum recommended human dose (mrhd). additionally, administration of varenicline to pregnant rats during organogenesis through lactation produced developmental toxicity in offspring at maternal exposures equivalent to 36 times human exposure at the mrhd [see data] . the estimated background risk of oral clefts is increased by approximately 30% in infants of women who smoke during pregnancy, compared to pregnant women who do not smoke. the background risk of other major birth defects and miscarriage for the indicated population are unknown. in the us 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 smoking during pregnancy causes increased risks of orofacial clefts, premature rupture of membranes, placenta previa, placental abruption, ectopic pregnancy, fetal growth restriction and low birth weight, stillbirth, preterm delivery and shortened gestation, neonatal death, sudden infant death syndrome and reduction of lung function in infants. it is not known whether quitting smoking with chantix during pregnancy reduces these risks. data human data a population-based observational cohort study using the national registers of denmark and sweden compared pregnancy and birth outcomes among women exposed to varenicline (n=335, includes 317 first trimester exposed) with women who smoked during pregnancy (n=78,412) and with non-smoking pregnant women (n=806,438). the prevalence of major malformations, the primary outcome, was similar in all groups, including between smoking and non-smoking groups. the prevalence of adverse perinatal outcomes in the varenicline-exposed cohort was not greater than in the cohort of women who smoked, and differed somewhat between the three cohorts. the prevalences of the primary and secondary outcomes are shown in table 6. major congenital malformation* 12 / 334 (3.6%) 3,382 / 78,028 (4.3%) 33,950 /804,020 (4.2%) stillbirth 1 (0.3%) 384 (0.5%) 2,418 (0.3%) small for gestational age 42 (12.5%) 13,433 (17.1%) 73,135 (9.1%) preterm birth 25 (7.5%) 6,173 (7.9%) 46,732 (5.8%) premature rupture of membranes 12 (3.6%) 4,246 (5.4%) 30,641 (3.8%) sudden infant death syndrome† 0/307 (0.0%) 51/71,720 (0.1%) 58/755,939 (<0.1%) the study limitations include the inability to capture malformations in pregnancies that do not result in a live birth, and possible misclassification of outcome and of exposure to varenicline or to smoking. other small epidemiological studies of pregnant women exposed to varenicline did not identify an association with major malformations, consistent with the danish and swedish observational cohort study. methodological limitations of these studies include small samples and lack of adequate controls. overall, available studies cannot definitely establish or exclude any varenicline-associated risk during pregnancy. animal data pregnant rats and rabbits received varenicline succinate during organogenesis at oral doses up to 15 and 30 mg/kg/day, respectively. while no fetal structural abnormalities occurred in either species, maternal toxicity, characterized by reduced body weight gain, and reduced fetal weights occurred in rabbits at the highest dose (exposures 50 times the human exposure at the mrhd of 1 mg twice daily based on auc). fetal weight reduction did not occur in rabbits at exposures 23 times the human exposure at the mrhd based on auc. in a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate from organogenesis through lactation. maternal toxicity, characterized by a decrease in body weight gain was observed at 15 mg/kg/day (36 times the human exposure at the mrhd based on auc). however, decreased fertility and increased auditory startle response occurred in offspring at the highest maternal dose of 15 mg/kg/day.       risk summary there are no data on the presence of varenicline in human milk, the effects on the breastfed infant, or the effects on milk production. in animal studies varenicline was present in milk of lactating rats [see data] . however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. the lack of clinical data during lactation precludes a clear determination of the risk of chantix to an infant during lactation; however the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for chantix and any potential adverse effects on the breastfed child from chantix or from the underlying maternal condition. clinical considerations because there are no data on the presence of varenicline in human milk and the effects on the breastfed infant, breastfeeding women should monitor their infant for seizures and excessive vomiting, which are adverse reactions that have occurred in adults that may be clinically relevant in breastfeeding infants. data in a pre- and postnatal development study, pregnant rats received up to 15 mg/kg/day of oral varenicline succinate through gestation and lactation mean serum concentrations of varenicline in the nursing pups were 5–22% of maternal serum concentrations. chantix is not recommended for use in pediatric patients 16 years of age or younger because its efficacy in this population was not demonstrated. single and multiple-dose pharmacokinetics of varenicline have been investigated in pediatric patients aged 12 to 17 years old (inclusive) and were approximately dose-proportional over the 0.5 mg to 2 mg daily dose range studied. steady-state systemic exposure in adolescent patients of bodyweight >55 kg, as assessed by auc (0-24), was comparable to that noted for the same doses in the adult population. when 0.5 mg bid was given, steady-state daily exposure of varenicline was, on average, higher (by approximately 40%) in adolescent patients with bodyweight ≤55 kg compared to that noted in the adult population. the efficacy and safety of varenicline was evaluated in a randomized, double-blind, placebo-controlled study of 312 patients aged 12 to 19 years, who smoked an average of at least 5 cigarettes per day during the 30 days prior to recruitment, had a score of at least 4 on the fagerstrom test for nicotine dependence scale, and at least one previous failed quit attempt. patients were stratified by age (12 to 16 years of age, n=216 and 17 to 19 years of age, n=96) and by body weight (≤55 kg and >55 kg). patients were randomized to one of two doses of varenicline, adjusted by weight to provide plasma levels in the efficacious range (based on adult studies) and placebo. patients received treatment for 12 weeks, followed by a non-treatment period of 40 weeks, along with age-appropriate counseling throughout the study. results from this study showed that varenicline, at either dose studied, did not improve continuous abstinence rates at weeks 9 through 12 of treatment compared with placebo in subjects 12 to 19 years of age. the varenicline safety profile in this study was consistent with that observed in adult studies. a combined single- and multiple-dose pharmacokinetic study demonstrated that the pharmacokinetics of 1 mg varenicline given once daily or twice daily to 16 healthy elderly male and female smokers (aged 65–75 years) for 7 consecutive days was similar to that of younger subjects. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. varenicline is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see dosage and administration (2.2)] . no dosage adjustment is recommended for elderly patients. varenicline is substantially eliminated by renal glomerular filtration along with active tubular secretion. dose reduction is not required in patients with mild to moderate renal impairment. for patients with severe renal impairment (estimated creatinine clearance <30 ml/min), and for patients with end-stage renal disease undergoing hemodialysis, dosage adjustment is needed [see dosage and administration (2.2), clinical pharmacology (12.3)].       varenicline is not a controlled substance.       humans fewer than 1 out of 1,000 patients reported euphoria in clinical trials with chantix. at higher doses (greater than 2 mg), chantix produced more frequent reports of gastrointestinal disturbances such as nausea and vomiting. there is no evidence of dose-escalation to maintain therapeutic effects in clinical studies, which suggests that tolerance does not develop. abrupt discontinuation of chantix was associated with an increase in irritability and sleep disturbances in up to 3% of patients. this suggests that, in some patients, varenicline may produce mild physical dependence which is not associated with addiction. in a human laboratory abuse liability study, a single oral dose of 1 mg varenicline did not produce any significant positive or negative subjective responses in smokers. in non-smokers, 1 mg varenicline produced an increase in some positive subjective effects, but this was accompanied by an increase in negative adverse effects, especially nausea. a single oral dose of 3 mg varenicline uniformly produced unpleasant subjective responses in both smokers and non-smokers. animals studies in rodents have shown that varenicline produces behavioral responses similar to those produced by nicotine. in rats trained to discriminate nicotine from saline, varenicline produced full generalization to the nicotine cue. in self-administration studies, the degree to which varenicline substitutes for nicotine is dependent upon the requirement of the task. rats trained to self-administer nicotine under easy conditions continued to self-administer varenicline to a degree comparable to that of nicotine; however in a more demanding task, rats self-administered varenicline to a lesser extent than nicotine. varenicline pretreatment also reduced nicotine self-administration.

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - zaleplon (unii: s62u433rmh) (zaleplon - unii:s62u433rmh) - zaleplon 5 mg - sonata is indicated for the short-term treatment of insomnia. sonata has been shown to decrease the time to sleep onset for up to 30 days in controlled clinical studies (see clinical trials under clinical pharmacology ). it has not been shown to increase total sleep time or decrease the number of awakenings. the clinical trials performed in support of efficacy ranged from a single night to 5 weeks in duration. the final formal assessments of sleep latency were performed at the end of treatment. hypersensitivity to zaleplon or any excipients in the formulation (see also precautions ). sonata is classified as a schedule iv controlled substance by federal regulation. abuse and addiction are separate and distinct from physical dependence and tolerance. abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. physical dependence is a state of adaption that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - adalimumab (unii: fys6t7f842) (adalimumab - unii:fys6t7f842) - abrilada is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. abrilada can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (dmards). abrilada is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. abrilada can be used alone or in combination with methotrexate. abrilada is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. abrilada can be used alone or in combination with non-biologic dmards. abrilada is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. abrilada is indicated for the treatment of moderately to severely active crohn's disease in adults and pediatric patients 6 years of age and older. abrilada is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. limitations of use the effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to tnf blockers [see clinical studies (14.7)] . abrilada is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. abrilada should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see warnings and precautions (5)] . abrilada is indicated for the treatment of moderate to severe hidradenitis suppurativa in adult patients. abrilada is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adult patients. none. risk summary available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. clinical data are available from the organization of teratology information specialists (otis)/mothertobaby pregnancy registry in pregnant women with rheumatoid arthritis (ra) or crohn's disease (cd) treated with adalimumab. registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with ra or cd and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. the lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (see data). adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant (see clinical considerations). in an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (mrhd) of 40 mg subcutaneous without methotrexate (see data). the estimated background risk of major birth defects and miscarriage for the indicated populations 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 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and embryo/fetal risk published data suggest that the risk of adverse pregnancy outcomes in women with ra or inflammatory bowel disease (ibd) is associated with increased disease activity. adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. fetal/neonatal adverse reactions monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester (see data) . risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to adalimumab products in utero [see use in specific populations (8.4)] . data human data a prospective cohort pregnancy exposure registry conducted by otis/mothertobaby in the u.s. and canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 ra, 152 cd) treated with adalimumab during the first trimester and 106 women (74 ra, 32 cd) not treated with adalimumab. the proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% ra, 10.5% cd) and 7.5% (6.8% ra, 9.4% cd), respectively. the lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. this study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design. in an independent clinical study conducted in ten pregnant women with ibd treated with adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. the last dose of adalimumab was given between 1 and 56 days prior to delivery. adalimumab concentrations were 0.16–19.7 mcg/ml in cord blood, 4.28–17.7 mcg/ml in infant serum, and 0–16.1 mcg/ml in maternal serum. in all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. in addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 mcg/ml), 7 weeks (1.31 mcg/ml), 8 weeks (0.93 mcg/ml), and 11 weeks (0.53 mcg/ml), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth. animal data in an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the mrhd without methotrexate (on an auc basis with maternal iv doses up to 100 mg/kg/week). adalimumab did not elicit harm to the fetuses or malformations. risk summary limited data from case reports in the published literature describe the presence of adalimumab in human milk at infant doses of 0.1% to 1% of the maternal serum concentration. published data suggest that the systemic exposure to a breastfed infant is expected to be low because adalimumab is a large molecule and is degraded in the gastrointestinal tract. however, the effects of local exposure in the gastrointestinal tract are unknown. there are no reports of adverse effects of adalimumab products on the breastfed infant and no effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for abrilada and any potential adverse effects on the breastfed child from abrilada or from the underlying maternal condition. the safety and effectiveness of abrilada have been established for: pediatric assessments for abrilada demonstrate that abrilada is safe and effective for pediatric patients in indications for which humira (adalimumab) is approved. however, abrilada is not approved for such indications due to marketing exclusivity for humira (adalimumab). due to their inhibition of tnfα, adalimumab products administered during pregnancy could affect immune response in the in utero -exposed newborn and infant. data from eight infants exposed to adalimumab in utero suggest adalimumab crosses the placenta [see use in specific populations (8.1)] . the clinical significance of elevated adalimumab concentrations in infants is unknown. the safety of administering live or live-attenuated vaccines in exposed infants is unknown. risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. postmarketing cases of lymphoma, including hepatosplenic t-cell lymphoma and other malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with tnf-blockers including adalimumab products [see warnings and precautions (5.2)] . juvenile idiopathic arthritis in study jia-i, adalimumab was shown to reduce signs and symptoms of active polyarticular jia in patients 4 to 17 years of age [see clinical studies (14.2)] . in study jia-ii, the safety profile for patients 2 to <4 years of age was similar to the safety profile for patients 4 to 17 years of age with polyarticular jia [see adverse reactions (6.1)] . adalimumab products have not been studied in patients with polyarticular jia less than 2 years of age or in patients with a weight below 10 kg. the safety of adalimumab in patients in the polyarticular jia trials was generally similar to that observed in adults with certain exceptions [see adverse reactions (6.1)] . the safety and effectiveness of adalimumab products have not been established in pediatric patients with jia less than 2 years of age. pediatric crohn's disease the safety and effectiveness of adalimumab products for the treatment of moderately to severely active crohn's disease have been established in pediatric patients 6 years of age and older. use of adalimumab products for this indication is supported by evidence from adequate and well-controlled studies in adults with additional data from a randomized, double-blind, 52-week clinical study of two dose concentrations of adalimumab in 192 pediatric patients (6 years to 17 years of age) [see adverse reactions (6.1), clinical pharmacology (12.2, 12.3), clinical studies (14.6)] . the adverse reaction profile in patients 6 years to 17 years of age was similar to adults. the safety and effectiveness of adalimumab products have not been established in pediatric patients with crohn's disease less than 6 years of age. a total of 519 ra patients 65 years of age and older, including 107 patients 75 years of age and older, received adalimumab in clinical studies ra-i through iv. no overall difference in effectiveness was observed between these patients and younger patients. the frequency of serious infection and malignancy among adalimumab-treated patients 65 years of age and older was higher than for those less than 65 years of age. consider the benefits and risks of abrilada in patients 65 years of age and older. in patients treated with abrilada, closely monitor for the development of infection or malignancy [see warnings and precautions (5.1, 5.2)] . abrilada (ah brill-ah-dah) (adalimumab-afzb) 40 mg/0.8 ml single-dose prefilled pen injection, for subcutaneous (under the skin) use keep this leaflet. these instructions show step by step directions on how to prepare and give an injection. storage information: keep abrilada, injection supplies, and all other medicines out of the reach of children. abrilada for injection comes in a disposable (throw away) single-use pen that contains a single dose of medicine. abrilada for injection can be given by a patient, caregiver or healthcare provider. do not try to inject abrilada yourself until you are shown the right way to give the injections and read and understand the instructions for use. if your healthcare provider decides that you or a caregiver may be able to give your injections of abrilada at home, you should receive training on the right way to prepare and inject abrilada. it is important that you read, understand, and follow these instructions so that you inject abrilada the right way. it is important to talk to your healthcare provider to be sure you understand your abrilada dosing instructions. to help you remember when to inject abrilada, you can mark your calendar ahead of time. call your healthcare provider if you or your caregiver have any questions about the right way to inject abrilada. step 1. supplies you need step 2. getting ready   questions and answers what should i do with my pen if it has been dropped? do not use it, even if it looks undamaged. dispose of your pen in the same way as a used pen. you will need to use a new pen to give your injection. can i use my pen straight from the refrigerator? yes, however you may find that using the pen at room temperature reduces stinging or discomfort. if you allow your pen to reach room temperature before use, you must keep it away from direct sunlight as this can damage your medicine. what should i do if i need to travel? when you are traveling, you may store your pen in its carton at room temperature up to 86°f (30°c) for up to 30 days. is it okay to shake my pen before i use it? no, do not shake your pen. shaking can damage your medicine. when you check your medicine, gently tilt your pen back and forth while looking carefully into the window. it is normal to see one or more air bubbles. do i need to remove any air bubbles before using my pen? no, do not attempt to remove air bubbles. drops of medicine have appeared at the needle tip. is this okay? yes, it is normal to see a few drops of medicine at the needle tip when you remove the cap. can i re-insert the needle if i change my mind where i want to inject? no, you should not re-insert the needle into your skin. if you change your mind, you will need a replacement pen if the needle has already been inserted into the skin. after the injection button has been pressed, you must not lift your pen from the skin until the injection has finished. i pushed my pen against the skin but could not press the button down. what should i do? take your finger off the injection button and push your pen down more firmly against the skin. then try pushing the button again. if this does not work, stretching the skin may make the injection site firmer, making pressing the injection button easier. can i pinch or stretch the skin at the injection area? yes, pinching or stretching the skin before injection may make the injection site firmer, making it easier to press the injection button. do i need to keep my finger pressed on the injection button for the whole injection? no, you can stop pressing the button when the injection has started. however, make sure you keep holding the pen firmly against the skin. the pen will continue to deliver your medicine. how long will the injection take? from the time the dose begins until you hear the 2nd click, it usually takes 3 to 10 seconds. after the 2nd click, you should continue to hold your pen in place for at least 5 more seconds to make sure you give the full dose. what should i do if i see more than a small drop of medicine on the skin after giving my injection? nothing this time, but for your next injection wait a little longer before removing the pen from the skin to make sure all of the medicine went into your skin. what should i do if i have any questions about my abrilada pen or medicine? contact your healthcare provider or pharmacist. this instructions for use has been approved by the u.s. food and drug administration. manufactured by pfizer inc. new york, ny 10001 distributed by pfizer labs division of pfizer inc. new york, ny 10001 us license no. 2001 lab-1352-3.0 revised: 06/2023 abrilada (ah brill-ah-dah) (adalimumab-afzb) 10 mg/0.2 ml, 20 mg/0.4 ml, 40 mg/0.8 ml single-dose prefilled syringe injection, for subcutaneous (under the skin) use only keep this leaflet. these instructions show step by step directions on how to prepare and give an injection. storage information: keep abrilada, injection supplies, and all other medicines out of the reach of children. abrilada for injection comes in a disposable (throw away) single use prefilled syringe that contains a single dose of medicine. abrilada for injection can be given by a patient, caregiver or healthcare provider. do not try to inject abrilada yourself until you are shown the right way to give the injections and read and understand the instructions for use. if your healthcare provider decides that you or a caregiver may be able to give your injections of abrilada at home, you should receive training on the right way to prepare and inject abrilada. it is important that you read, understand, and follow these instructions so that you inject abrilada the right way. it is important to talk to your healthcare provider to be sure you understand your abrilada dosing instructions. to help you remember when to inject abrilada, you can mark your calendar ahead of time. call your healthcare provider if you or your caregiver have any questions about the right way to inject abrilada. step 1. supplies you need step 2. getting ready wash your hands with soap and water, and dry completely. if you have any questions about your medicine, please contact your healthcare provider or pharmacist.   questions and answers what should i do with my prefilled syringe if it has been dropped? do not use it if it has been dropped or the carton containing your prefilled syringe has been dropped even if it looks undamaged. dispose of your prefilled syringe in the same way as a used prefilled syringe. you will need to use a new prefilled syringe to give your injection. can i use my prefilled syringe straight from the refrigerator? yes, however you may find that using the prefilled syringe at room temperature reduces stinging or discomfort. if you allow your prefilled syringe to reach room temperature before use, you must keep it away from direct sunlight as this can damage your medicine. what should i do if i need to travel? when you are traveling, you may store your prefilled syringe in its carton at room temperature up to 86°f (30°c) for up to 30 days. is it okay to shake my prefilled syringe before i use it? no, do not shake your prefilled syringe. shaking can damage your medicine. when you check your medicine, gently tilt your syringe back and forth while looking carefully into the window. it is normal to see one or more bubbles. do i need to remove any air bubbles before using my prefilled syringe? no, do not attempt to remove air bubbles. drops of medicine have appeared at the needle tip. is this okay? yes, it is normal to see a few drops of medicine at the needle tip when you remove the needle cover. can i re-insert the needle into my skin? no, you should not re-insert the needle into the skin. you will need a replacement prefilled syringe if the needle has already been inserted into the skin. how long will the injection take? dose delivery will take approximately 2 to 5 seconds. remember to hold your prefilled syringe in place for at least 5 seconds after the plunger has been pushed down all the way. what should i do if i have any questions about my prefilled syringe or medicine? contact your healthcare provider or pharmacist. this instructions for use has been approved by the u.s. food and drug administration. manufactured by pfizer inc. new york, ny 10001 distributed by pfizer labs division of pfizer inc. new york, ny 10001 us license no. 2001 lab-1353-3.0 revised: 06/2023

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - adalimumab (unii: fys6t7f842) (adalimumab - unii:fys6t7f842) - abrilada is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. abrilada can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (dmards). abrilada is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. abrilada can be used alone or in combination with methotrexate. abrilada is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. abrilada can be used alone or in combination with non-biologic dmards. abrilada is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. abrilada is indicated for the treatment of moderately to severely active crohn's disease in adults and pediatric patients 6 years of age and older. abrilada is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. limitations of use the effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to tnf blockers [see clinical studies (14.7)] . abrilada is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. abrilada should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see warnings and precautions (5)] . abrilada is indicated for the treatment of moderate to severe hidradenitis suppurativa in adult patients. abrilada is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adult patients. none. risk summary available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. clinical data are available from the organization of teratology information specialists (otis)/mothertobaby pregnancy registry in pregnant women with rheumatoid arthritis (ra) or crohn's disease (cd) treated with adalimumab. registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with ra or cd and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. the lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (see data). adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant (see clinical considerations). in an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (mrhd) of 40 mg subcutaneous without methotrexate (see data). the estimated background risk of major birth defects and miscarriage for the indicated populations 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 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and embryo/fetal risk published data suggest that the risk of adverse pregnancy outcomes in women with ra or inflammatory bowel disease (ibd) is associated with increased disease activity. adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. fetal/neonatal adverse reactions monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester (see data) . risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to adalimumab products in utero [see use in specific populations (8.4)] . data human data a prospective cohort pregnancy exposure registry conducted by otis/mothertobaby in the u.s. and canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 ra, 152 cd) treated with adalimumab during the first trimester and 106 women (74 ra, 32 cd) not treated with adalimumab. the proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% ra, 10.5% cd) and 7.5% (6.8% ra, 9.4% cd), respectively. the lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. this study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design. in an independent clinical study conducted in ten pregnant women with ibd treated with adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. the last dose of adalimumab was given between 1 and 56 days prior to delivery. adalimumab concentrations were 0.16–19.7 mcg/ml in cord blood, 4.28–17.7 mcg/ml in infant serum, and 0–16.1 mcg/ml in maternal serum. in all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. in addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 mcg/ml), 7 weeks (1.31 mcg/ml), 8 weeks (0.93 mcg/ml), and 11 weeks (0.53 mcg/ml), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth. animal data in an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the mrhd without methotrexate (on an auc basis with maternal iv doses up to 100 mg/kg/week). adalimumab did not elicit harm to the fetuses or malformations. risk summary limited data from case reports in the published literature describe the presence of adalimumab in human milk at infant doses of 0.1% to 1% of the maternal serum concentration. published data suggest that the systemic exposure to a breastfed infant is expected to be low because adalimumab is a large molecule and is degraded in the gastrointestinal tract. however, the effects of local exposure in the gastrointestinal tract are unknown. there are no reports of adverse effects of adalimumab products on the breastfed infant and no effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for abrilada and any potential adverse effects on the breastfed child from abrilada or from the underlying maternal condition. the safety and effectiveness of abrilada have been established for: pediatric assessments for abrilada demonstrate that abrilada is safe and effective for pediatric patients in indications for which humira (adalimumab) is approved. however, abrilada is not approved for such indications due to marketing exclusivity for humira (adalimumab). due to their inhibition of tnfα, adalimumab products administered during pregnancy could affect immune response in the in utero -exposed newborn and infant. data from eight infants exposed to adalimumab in utero suggest adalimumab crosses the placenta [see use in specific populations (8.1)] . the clinical significance of elevated adalimumab concentrations in infants is unknown. the safety of administering live or live-attenuated vaccines in exposed infants is unknown. risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. postmarketing cases of lymphoma, including hepatosplenic t-cell lymphoma and other malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with tnf-blockers including adalimumab products [see warnings and precautions (5.2)] . juvenile idiopathic arthritis in study jia-i, adalimumab was shown to reduce signs and symptoms of active polyarticular jia in patients 4 to 17 years of age [see clinical studies (14.2)] . in study jia-ii, the safety profile for patients 2 to <4 years of age was similar to the safety profile for patients 4 to 17 years of age with polyarticular jia [see adverse reactions (6.1)] . adalimumab products have not been studied in patients with polyarticular jia less than 2 years of age or in patients with a weight below 10 kg. the safety of adalimumab in patients in the polyarticular jia trials was generally similar to that observed in adults with certain exceptions [see adverse reactions (6.1)] . the safety and effectiveness of adalimumab products have not been established in pediatric patients with jia less than 2 years of age. pediatric crohn's disease the safety and effectiveness of adalimumab products for the treatment of moderately to severely active crohn's disease have been established in pediatric patients 6 years of age and older. use of adalimumab products for this indication is supported by evidence from adequate and well-controlled studies in adults with additional data from a randomized, double-blind, 52-week clinical study of two dose concentrations of adalimumab in 192 pediatric patients (6 years to 17 years of age) [see adverse reactions (6.1), clinical pharmacology (12.2, 12.3), clinical studies (14.6)] . the adverse reaction profile in patients 6 years to 17 years of age was similar to adults. the safety and effectiveness of adalimumab products have not been established in pediatric patients with crohn's disease less than 6 years of age. a total of 519 ra patients 65 years of age and older, including 107 patients 75 years of age and older, received adalimumab in clinical studies ra-i through iv. no overall difference in effectiveness was observed between these patients and younger patients. the frequency of serious infection and malignancy among adalimumab-treated patients 65 years of age and older was higher than for those less than 65 years of age. consider the benefits and risks of abrilada in patients 65 years of age and older. in patients treated with abrilada, closely monitor for the development of infection or malignancy [see warnings and precautions (5.1, 5.2)] . abrilada (ah brill-ah-dah) (adalimumab-afzb) 40 mg/0.8 ml single-dose prefilled pen injection, for subcutaneous (under the skin) use keep this leaflet. these instructions show step by step directions on how to prepare and give an injection. storage information: keep abrilada, injection supplies, and all other medicines out of the reach of children. abrilada for injection comes in a disposable (throw away) single-use pen that contains a single dose of medicine. abrilada for injection can be given by a patient, caregiver or healthcare provider. do not try to inject abrilada yourself until you are shown the right way to give the injections and read and understand the instructions for use. if your healthcare provider decides that you or a caregiver may be able to give your injections of abrilada at home, you should receive training on the right way to prepare and inject abrilada. it is important that you read, understand, and follow these instructions so that you inject abrilada the right way. it is important to talk to your healthcare provider to be sure you understand your abrilada dosing instructions. to help you remember when to inject abrilada, you can mark your calendar ahead of time. call your healthcare provider if you or your caregiver have any questions about the right way to inject abrilada. step 1. supplies you need step 2. getting ready   questions and answers what should i do with my pen if it has been dropped? do not use it, even if it looks undamaged. dispose of your pen in the same way as a used pen. you will need to use a new pen to give your injection. can i use my pen straight from the refrigerator? yes, however you may find that using the pen at room temperature reduces stinging or discomfort. if you allow your pen to reach room temperature before use, you must keep it away from direct sunlight as this can damage your medicine. what should i do if i need to travel? when you are traveling, you may store your pen in its carton at room temperature up to 86°f (30°c) for up to 30 days. is it okay to shake my pen before i use it? no, do not shake your pen. shaking can damage your medicine. when you check your medicine, gently tilt your pen back and forth while looking carefully into the window. it is normal to see one or more air bubbles. do i need to remove any air bubbles before using my pen? no, do not attempt to remove air bubbles. drops of medicine have appeared at the needle tip. is this okay? yes, it is normal to see a few drops of medicine at the needle tip when you remove the cap. can i re-insert the needle if i change my mind where i want to inject? no, you should not re-insert the needle into your skin. if you change your mind, you will need a replacement pen if the needle has already been inserted into the skin. after the injection button has been pressed, you must not lift your pen from the skin until the injection has finished. i pushed my pen against the skin but could not press the button down. what should i do? take your finger off the injection button and push your pen down more firmly against the skin. then try pushing the button again. if this does not work, stretching the skin may make the injection site firmer, making pressing the injection button easier. can i pinch or stretch the skin at the injection area? yes, pinching or stretching the skin before injection may make the injection site firmer, making it easier to press the injection button. do i need to keep my finger pressed on the injection button for the whole injection? no, you can stop pressing the button when the injection has started. however, make sure you keep holding the pen firmly against the skin. the pen will continue to deliver your medicine. how long will the injection take? from the time the dose begins until you hear the 2nd click, it usually takes 3 to 10 seconds. after the 2nd click, you should continue to hold your pen in place for at least 5 more seconds to make sure you give the full dose. what should i do if i see more than a small drop of medicine on the skin after giving my injection? nothing this time, but for your next injection wait a little longer before removing the pen from the skin to make sure all of the medicine went into your skin. what should i do if i have any questions about my abrilada pen or medicine? contact your healthcare provider or pharmacist. this instructions for use has been approved by the u.s. food and drug administration. manufactured by pfizer inc. new york, ny 10001 distributed by pfizer labs division of pfizer inc. new york, ny 10001 us license no. 2001 lab-1352-3.0 revised: 06/2023 abrilada (ah brill-ah-dah) (adalimumab-afzb) 10 mg/0.2 ml, 20 mg/0.4 ml, 40 mg/0.8 ml single-dose prefilled syringe injection, for subcutaneous (under the skin) use only keep this leaflet. these instructions show step by step directions on how to prepare and give an injection. storage information: keep abrilada, injection supplies, and all other medicines out of the reach of children. abrilada for injection comes in a disposable (throw away) single use prefilled syringe that contains a single dose of medicine. abrilada for injection can be given by a patient, caregiver or healthcare provider. do not try to inject abrilada yourself until you are shown the right way to give the injections and read and understand the instructions for use. if your healthcare provider decides that you or a caregiver may be able to give your injections of abrilada at home, you should receive training on the right way to prepare and inject abrilada. it is important that you read, understand, and follow these instructions so that you inject abrilada the right way. it is important to talk to your healthcare provider to be sure you understand your abrilada dosing instructions. to help you remember when to inject abrilada, you can mark your calendar ahead of time. call your healthcare provider if you or your caregiver have any questions about the right way to inject abrilada. step 1. supplies you need step 2. getting ready wash your hands with soap and water, and dry completely. if you have any questions about your medicine, please contact your healthcare provider or pharmacist.   questions and answers what should i do with my prefilled syringe if it has been dropped? do not use it if it has been dropped or the carton containing your prefilled syringe has been dropped even if it looks undamaged. dispose of your prefilled syringe in the same way as a used prefilled syringe. you will need to use a new prefilled syringe to give your injection. can i use my prefilled syringe straight from the refrigerator? yes, however you may find that using the prefilled syringe at room temperature reduces stinging or discomfort. if you allow your prefilled syringe to reach room temperature before use, you must keep it away from direct sunlight as this can damage your medicine. what should i do if i need to travel? when you are traveling, you may store your prefilled syringe in its carton at room temperature up to 86°f (30°c) for up to 30 days. is it okay to shake my prefilled syringe before i use it? no, do not shake your prefilled syringe. shaking can damage your medicine. when you check your medicine, gently tilt your syringe back and forth while looking carefully into the window. it is normal to see one or more bubbles. do i need to remove any air bubbles before using my prefilled syringe? no, do not attempt to remove air bubbles. drops of medicine have appeared at the needle tip. is this okay? yes, it is normal to see a few drops of medicine at the needle tip when you remove the needle cover. can i re-insert the needle into my skin? no, you should not re-insert the needle into the skin. you will need a replacement prefilled syringe if the needle has already been inserted into the skin. how long will the injection take? dose delivery will take approximately 2 to 5 seconds. remember to hold your prefilled syringe in place for at least 5 seconds after the plunger has been pushed down all the way. what should i do if i have any questions about my prefilled syringe or medicine? contact your healthcare provider or pharmacist. this instructions for use has been approved by the u.s. food and drug administration. manufactured by pfizer inc. new york, ny 10001 distributed by pfizer labs division of pfizer inc. new york, ny 10001 us license no. 2001 lab-1353-3.0 revised: 06/2023

Statele Unite ale Americii - engleză - 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)] .

Statele Unite ale Americii - engleză - 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) ].

Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - sunitinib malate (unii: lvx8n1ut73) (sunitinib - unii:v99t50803m) - sunitinib 12.5 mg - sutent is indicated for the treatment of adult patients with gastrointestinal stromal tumor (gist) after disease progression on or intolerance to imatinib mesylate. sutent is indicated for the treatment of adult patients with advanced renal cell carcinoma (rcc). sutent is indicated for the adjuvant treatment of adult patients at high risk of recurrent rcc following nephrectomy. sutent is indicated for the treatment of progressive, well-differentiated pancreatic neuroendocrine tumors (pnet) in adult patients with unresectable locally advanced or metastatic disease. none. risk summary based on animal reproduction studies and its mechanism of action, sutent can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data in pregnant women to inform a drug-associated risk. in animal developmental and reproductive toxicology studies, oral administration of sunitinib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity (embryolet