Egyesült Államok - angol - NLM (National Library of Medicine)

remedyrepack inc. - salmeterol xinafoate (unii: 6ew8q962a5) (salmeterol - unii:2i4bc502bt), fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u) - advair diskus is indicated for the twice-daily treatment of asthma in patients aged 4 years and older. advair diskus should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta 2 -adrenergic agonist (laba). important limitation of use advair diskus is not indicated for the relief of acute bronchospasm. advair diskus 250/50 is indicated for the twice-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (copd), including chronic bronchitis and/or emphysema. advair diskus 250/50 is also indicated to reduce exacerbations of copd in patients with a history of exacerbations. advair diskus 250/50 twice daily is the only approved dosage for the treatment of copd because an efficacy advantage of the higher strength advair diskus 500/50 over advair diskus 250/50 has not been demonstrated. impo

Egyesült Államok - angol - NLM (National Library of Medicine)

remedyrepack inc. - fluticasone furoate (unii: js86977wnv) (fluticasone - unii:cut2w21n7u), vilanterol trifenatate (unii: 40aho2c6dg) (vilanterol - unii:028lzy775b) - breo ellipta 100/25 is indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (copd), including chronic bronchitis and/or emphysema. breo ellipta 100/25 is also indicated to reduce exacerbations of copd in patients with a history of exacerbations. breo ellipta 100/25 once daily is the only strength indicated for the treatment of copd. important limitation of use breo ellipta is not indicated for the relief of acute bronchospasm. breo ellipta is indicated for the once-daily treatment of asthma in patients aged 18 years and older. breo ellipta should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta 2 -adrenergic agonist (laba). important limitation of use breo ellipta is not indicated for the relief of acute bronchospasm. the use of breo ellipta is

Egyesült Államok - angol - NLM (National Library of Medicine)

proficient rx lp - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u), salmeterol xinafoate (unii: 6ew8q962a5) (salmeterol - unii:2i4bc502bt) - fluticasone propionate/salmeterol diskus is indicated for the twice-daily treatment of asthma in patients aged 4 years and older. fluticasone propionate/salmeterol diskus should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta2 -adrenergic agonist (laba). important limitation of use fluticasone propionate/salmeterol diskus is not indicated for the relief of acute bronchospasm. fluticasone propionate/salmeterol diskus inhalation powder 250/50 mcg is indicated for the twice-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (copd), including chronic bronchitis and/or emphysema. fluticasone propionate/salmeterol diskus inhalation powder 250/50 mcg is also indicated to reduce exacerbations of copd in patients with a history of exacerbations. fluticasone propionate/salmeterol diskus inhalation po

Egyesült Államok - angol - NLM (National Library of Medicine)

remedyrepack inc. - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u), salmeterol xinafoate (unii: 6ew8q962a5) (salmeterol - unii:2i4bc502bt) - wixela inhub ® is indicated for the twice-daily treatment of asthma in patients aged 4 years and older. wixela inhub ® should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta 2 -adrenergic agonist (laba). wixela inhub ® is not indicated for the relief of acute bronchospasm. wixela inhub ® 250/50 is indicated for the twice-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (copd), including chronic bronchitis and/or emphysema. wixela inhub ® 250/50 is also indicated to reduce exacerbations of copd in patients with a history of exacerbations. wixela inhub ® 250/50 twice daily is the only approved dosage for the treatment of copd because an efficacy advantage of the higher strength wixela inhub ® 500/50 over wixela inhub ® 250/50 has not been demonstrated. wixela inhub ® is not indicated for the relief of acute bronchospasm. the use of wixela inhub ® is contraindicated in the following conditions: - primary treatment of status asthmaticus or other acute episodes of asthma or copd where intensive measures are required [see warnings and precautions (5.2)] . - severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone propionate, salmeterol, or any of the excipients [see warnings and precautions (5.11), adverse reactions (6.3), description (11)] . there are insufficient data on the use of fluticasone propionate and salmeterol inhalation powder or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. there are clinical considerations with the use of fluticasone propionate and salmeterol inhalation powder in pregnant women (see clinical considerations) . in animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits were observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (mrhdid) on a mcg/m2 basis (see data) . however, fluticasone propionate administered via inhalation to rats decreased fetal body weight, but did not induce teratogenicity at a maternal toxic dose less than the mrhdid on a mcg/m2 basis (see data) . experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. oral administration of salmeterol to pregnant rabbits caused teratogenicity characteristic of beta-adrenoceptor stimulation at maternal doses approximately 50 times the mrhdid on an auc basis. these adverse effects generally occurred at large multiples of the mrhdid when salmeterol was administered by the oral route to achieve high systemic exposures. no such effects occurred at an oral salmeterol dose approximately 20 times the mrhdid (see data) . the estimated risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. disease-associated maternal and/or embryofetal risk: in women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma. there are no human studies evaluating the effects of fluticasone propionate and salmeterol inhalation powder during labor and delivery. because of the potential for beta-agonist interference with uterine contractility, use of wixela inhub ® during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery. in an embryofetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,000; 30/0; 10/100; 30/1,000; and 100/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. omphalocele, increased embryofetal deaths, decreased body weight, and skeletal variations were observed in rat fetuses in the presence of maternal toxicity when combining fluticasone propionate at a dose approximately equivalent to the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 100 mcg/kg/day) and salmeterol at a dose approximately 970 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 10,000 mcg/kg/day). the rat no observed adverse effect level (noael) was observed when combining fluticasone propionate at a dose approximately 0.3 times the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 30 mcg/kg/day) and salmeterol at a dose approximately 100 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 1,000 mcg/kg/day). in an embryofetal development study with pregnant mice that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,400; 40/0; 10/200; 40/1,400; or 150/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. cleft palate, fetal death, increased implantation loss, and delayed ossification were observed in mouse fetuses when combining fluticasone propionate at a dose approximately 0.7 times the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 150 mcg/kg/day) and salmeterol at a dose approximately 490 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 10,000 mcg/kg/day). no developmental toxicity was observed at combination doses of fluticasone propionate up to approximately 0.2 times the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 40 mcg/kg) and doses of salmeterol up to approximately 70 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 1,400 mcg/kg). in embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately equivalent to the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). the rat noael was observed at approximately 0.3 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 30 mcg/kg/day). cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 0.2 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). the mouse noael was observed with a dose approximately 0.07 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg/day). in an embryofetal development study with pregnant rats dosed by the inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 0.25 times the mrhdid (on a mcg/m2 basis with a maternal inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity. the noael was observed with a dose approximately 0.05 times the mrhdid (on a mcg/m2 basis with a maternal inhalation dose of 5.5 mcg/kg/day). in an embryofetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity, at doses approximately 0.012 times the mrhdid and higher (on a mcg/m2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day). teratogenicity was evident based upon a finding of cleft palate for 1 fetus at a dose approximately 0.08 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). the noael was observed in rabbit fetuses with a dose approximately 0.002 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day). fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits. in a pre- and post-natal development study in pregnant rats dosed by the subcutaneous route from late gestation through delivery and lactation (gestation day 17 to postpartum day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to 0.5 times the mrhdid (on a mcg/m 2 basis with maternal subcutaneous doses up to 50 mcg/kg/day). in 3 embryofetal development studies, pregnant rabbits received oral administration of salmeterol at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis. in pregnant dutch rabbits administered salmeterol doses approximately 50 times the mrhdid (on an auc basis at maternal oral doses of 1,000 mcg/kg/day and higher), fetal toxic effects were observed characteristically resulting from beta-adrenoceptor stimulation. these included precocious eyelid openings, cleft palate, sternebral fusion, limb and paw flexures, and delayed ossification of the frontal cranial bones. no such effects occurred at a salmeterol dose approximately 20 times the mrhdid (on an auc basis at a maternal oral dose of 600 mcg/kg/day). new zealand white rabbits were less sensitive since only delayed ossification of the frontal cranial bones was seen at a salmeterol dose approximately 2,000 times the mrhdid (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day). in 2 embryofetal development studies, pregnant rats received salmeterol by oral administration at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis. salmeterol produced no maternal toxicity or embryofetal effects at doses up to 973 times the mrhdid (on a mcg/m 2 basis at maternal oral doses up to 10,000 mcg/kg/day). in a peri- and post-natal development study in pregnant rats dosed by the oral route from late gestation through delivery and lactation, salmeterol at a dose 973 times the mrhdid (on a mcg/m 2 basis with a maternal oral dose of 10,000 mcg/kg/day) was fetotoxic and decreased the fertility of survivors. salmeterol xinafoate crossed the placenta following oral administration to mice and rats. there are no available data on the presence of fluticasone propionate or salmeterol in human milk, the effects on the breastfed child, or the effects on milk production. other corticosteroids have been detected in human milk. however, fluticasone propionate and salmeterol concentrations in plasma after inhaled therapeutic doses are low and therefore concentrations in human breast milk are likely to be correspondingly low [see clinical pharmacology (12.3)] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for wixela inhub ® and any potential adverse effects on the breastfed child from wixela inhub ® or from the underlying maternal condition. subcutaneous administration of tritiated fluticasone propionate at a dose of 10 mcg/kg/day to lactating rats resulted in measurable levels in milk. oral administration of salmeterol at a dose of 10,000 mcg/kg/day to lactating rats resulted in measurable levels in milk. use of fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg in patients aged 4 to 11 years is supported by extrapolation of efficacy data from older subjects and by safety and efficacy data from a trial of fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg in children with asthma aged 4 to 11 years [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1)] . the safety and effectiveness of fluticasone propionate and salmeterol inhalation powder in children with asthma younger than 4 years have not been established. ics, including fluticasone propionate, a component of wixela inhub ® , may cause a reduction in growth velocity in children and adolescents [see warnings and precautions (5.14)] . the growth of pediatric patients receiving orally inhaled corticosteroids, including wixela inhub ® , should be monitored. a 52-week placebo-controlled trial to assess the potential growth effects of fluticasone propionate inhalation powder (flovent ® rotadisk ® ) at 50 and 100 mcg twice daily was conducted in the u.s. in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years. the mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50 mcg group (n = 98), and 5.66 cm/year in the 100 mcg group (n = 89). an imbalance in the proportion of children entering puberty between groups and a higher dropout rate in the placebo group due to poorly controlled asthma may be confounding factors in interpreting these data. a separate subset analysis of children who remained prepubertal during the trial revealed growth rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mcg group (n = 74), and 5.67 cm/year in the 100-mcg group (n = 79). in children aged 8.5 years, the mean age of children in this trial, the range for expected growth velocity is: boys – 3 rd percentile = 3.8 cm/year, 50 th percentile = 5.4 cm/year, and 97 th percentile = 7.0 cm/year; girls – 3 rd percentile = 4.2 cm/year, 50 th percentile = 5.7 cm/year, and 97 th percentile = 7.3 cm/year. the clinical relevance of these growth data is not certain. if a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect of corticosteroids should be considered. the potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained. to minimize the systemic effects of orally inhaled corticosteroids, including wixela inhub ® , each patient should be titrated to the lowest strength that effectively controls his/her asthma [see dosage and administration (2.1)] . clinical trials of fluticasone propionate and salmeterol inhalation powder for asthma did not include sufficient numbers of subjects aged 65 years and older to determine whether older subjects with asthma respond differently than younger subjects. of the total number of subjects in clinical trials receiving fluticasone propionate and salmeterol inhalation powder for copd, 1,621 were aged 65 years and older and 379 were aged 75 years and older. subjects with copd aged 65 years and older had a higher incidence of serious adverse events compared with subjects younger than 65 years. although the distribution of adverse events was similar in the 2 age groups, subjects older than 65 years experienced more severe events. in two 1-year trials, the excess risk of pneumonia that was seen in subjects treated with fluticasone propionate and salmeterol inhalation powder compared with those treated with salmeterol was greater in subjects older than 65 years than in subjects younger than 65 years [see adverse reactions (6.2)] . as with other products containing beta 2 -agonists, special caution should be observed when using wixela inhub ® in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta 2 -agonists. based on available data for fluticasone propionate and salmeterol inhalation powder or its active components, no adjustment of dosage of wixela inhub ® in geriatric patients is warranted. no relationship between fluticasone propionate systemic exposure and age was observed in 57 subjects with copd (aged 40 to 82 years) given 250 or 500 mcg twice daily. formal pharmacokinetic studies using fluticasone propionate and salmeterol inhalation powder have not been conducted in patients with hepatic impairment. however, since both fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma. therefore, patients with hepatic disease should be closely monitored. formal pharmacokinetic studies using fluticasone propionate and salmeterol inhalation powder have not been conducted in patients with renal impairment. wixela inhub ® (wicks-el-uh in-hub) (fluticasone propionate and salmeterol inhalation powder, usp) for oral inhalation use read this instructions for use before you start using wixela inhub and each time you get a refill. there may be new information. this information does not take the place of talking to your healthcare provider about your medical condition or treatment. your wixela inhub inhaler closed position open position figure a figure b important information about your wixela inhub inhaler: - wixela inhub is for oral inhalation use only. - take wixela inhub out of the foil pouch just before you use it for the first time. safely throw away the pouch. the inhub will be in the closed position. see figure a. - write the date you opened the foil pouch in the first blank line on the label. see figure b. - write the “use by” date in the second blank line on the label. see figure b. that date is 1 month after the date you wrote in the first line. - the counter should read 60 . see figure a. how to use your wixela inhub inhaler follow these steps every time you use wixela inhub. step 1. open your wixela inhub. - hold the inhub in one hand and with your other hand on the grip lower the mouthpiece cover from top to bottom. see figure c. step 2. push down the lever. - hold the inhub in the vertical position. push the yellow lever down to the end of the purple arrows (you may hear a click). see figure d. - the inhub is now ready to use. - follow the instructions below so you will not accidentally waste a dose: - do not close the inhub. - do not move the lever on the inhub once pushed down. step 3. inhale your medicine. - before you breathe in your dose from the inhub, breathe out (exhale) as long as you can while you hold the inhub away from your mouth. see figure e. do not breathe into the mouthpiece. - put the mouthpiece to your lips. see figure f. breathe in quickly and deeply through the inhub. do not breathe in through your nose. - remove the inhub from your mouth and hold your breath for about 10 seconds, or for as long as is comfortable for you. - breathe out slowly for as long as you can. see figure e. - the inhub delivers your dose of medicine as a very fine powder that you may or may not taste or feel. do not take an extra dose from the inhub even if you do not taste or feel the medicine. step 4. close the inhub. - push the mouthpiece cover up to the closed position, this will automatically return the yellow lever to the start position. see figure g. make sure the inhub is shut and you cannot see the mouthpiece. - the dose counter will count down 1 dose as you close the mouthpiece cover. this will now tell you how many doses are left. - the inhub is now ready for you to take your next scheduled dose in about 12 hours. when you are ready to take your next dose, repeat steps 1 through 4. step 5. rinse your mouth. - rinse your mouth with water after breathing in the medicine. spit out the water. do not swallow it. see figure h. when should you get a refill? the dose counter on the inhub shows you how many doses are left. your dose counter will be set at 60 when you first receive your inhub. after you have taken 51 doses, a red indicator will be present. this indicator warns you there are 9 or fewer doses left and is a reminder to get a refill. the dose counter will read 0 and the lever will not reach the end of the purple arrows when there are no doses remaining. for correct use of the inhub, remember: - hold your breath for about 10 seconds after inhaling. then breathe out fully. - after each dose, rinse your mouth with water and spit it out. do not swallow the water. - do not take an extra dose, even if you did not taste or feel the powder. - do not take the inhub apart. - do not wash the inhub. - always keep the inhub in a dry place. - do not use the inhub with a spacer device. for more information about wixela inhub or how to use your inhaler, call mylan at 1-877-446-3679 (1-877-4-info-rx). the brands listed are trademarks of their respective owners. wixela inhub ® is a registered trademark of mylan pharmaceuticals inc., a viatris company. t this instructions for use has been approved by the u.s. food and drug administration. repackaged and distributed by: remedy repack, inc. 625 kolter dr. suite #4 indiana, pa 1-724-465-8762

Egyesült Államok - angol - NLM (National Library of Medicine)

hikma pharmaceuticals usa inc. - salmeterol xinafoate (unii: 6ew8q962a5) (salmeterol - unii:2i4bc502bt), fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u) - fluticasone propionate and salmeterol inhalation powder is indicated for the twice-daily treatment of asthma in patients aged 4 years and older. fluticasone propionate and salmeterol inhalation powder should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta2 -adrenergic agonist (laba). important limitation of use fluticasone propionate and salmeterol inhalation powder is not indicated for the relief of acute bronchospasm. fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg is indicated for the twice-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (copd), including chronic bronchitis and/or emphysema. fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg is also indicated to reduce exacerbations of copd in patients with a history of exacerbations. fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg twice daily is the only approved dosage for the treatment of copd because an efficacy advantage of the higher strength fluticasone propionate and salmeterol inhalation powder 500 mcg/50 mcg over fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg has not been demonstrated. important limitation of use fluticasone propionate and salmeterol inhalation powder is not indicated for the relief of acute bronchospasm. the use of fluticasone propionate and salmeterol inhalation powder is contraindicated in the following conditions: risk summary there are insufficient data on the use of fluticasone propionate and salmeterol inhalation powder or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. there are clinical considerations with the use of fluticasone propionate and salmeterol inhalation powder in pregnant women (see clinical considerations ). in animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits were observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (mrhdid) on a mcg/m2 basis (see data ). however, fluticasone propionate administered via inhalation to rats decreased fetal body weight, but did not induce teratogenicity at a maternal toxic dose less than the mrhdid on a mcg/m2 basis (see data ). experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. oral administration of salmeterol to pregnant rabbits caused teratogenicity characteristic of beta-adrenoceptor stimulation at maternal doses approximately 50 times the mrhdid on an auc basis. these adverse effects generally occurred at large multiples of the mrhdid when salmeterol was administered by the oral route to achieve high systemic exposures. no such effects occurred at an oral salmeterol dose approximately 20 times the mrhdid (see data ). the estimated risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk: in women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma. labor and delivery: there are no human studies evaluating the effects of fluticasone propionate and salmeterol inhalation powder during labor and delivery. because of the potential for beta-agonist interference with uterine contractility, use of fluticasone propionate and salmeterol inhalation powder during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. data human data: fluticasone propionate: following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery. animal data: fluticasone propionate and salmeterol: in an embryofetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,000; 30/0; 10/100; 30/1,000; and 100/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. omphalocele, increased embryofetal deaths, decreased body weight, and skeletal variations were observed in rat fetuses in the presence of maternal toxicity when combining fluticasone propionate at a dose approximately equivalent to the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 100 mcg/kg/day) and salmeterol at a dose approximately 970 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 10,000 mcg/kg/day). the rat no observed adverse effect level (noael) was observed when combining fluticasone propionate at a dose approximately 0.3 times the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 30 mcg/kg/day) and salmeterol at a dose approximately 100 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 1,000 mcg/kg/day). in an embryofetal development study with pregnant mice that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,400; 40/0; 10/200; 40/1,400; or 150/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. cleft palate, fetal death, increased implantation loss, and delayed ossification were observed in mouse fetuses when combining fluticasone propionate at a dose approximately 0.7 times the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 150 mcg/kg/day) and salmeterol at a dose approximately 490 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 10,000 mcg/kg/day). no developmental toxicity was observed at combination doses of fluticasone propionate up to approximately 0.2 times the mrhdid (on a mcg/m2 basis at a maternal subcutaneous dose of 40 mcg/kg) and doses of salmeterol up to approximately 70 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 1,400 mcg/kg). fluticasone propionate: in embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately equivalent to the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). the rat noael was observed at approximately 0.3 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 30 mcg/kg/day). cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 0.2 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). the mouse noael was observed with a dose approximately 0.07 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg/day). in an embryofetal development study with pregnant rats dosed by the inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 0.25 times the mrhdid (on a mcg/m2 basis with a maternal inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity. the noael was observed with a dose approximately 0.05 times the mrhdid (on a mcg/m2 basis with a maternal inhalation dose of 5.5 mcg/kg/day). in an embryofetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity, at doses approximately 0.012 times the mrhdid and higher (on a mcg/m2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day). teratogenicity was evident based upon a finding of cleft palate for 1 fetus at a dose approximately 0.08 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). the noael was observed in rabbit fetuses with a dose approximately 0.002 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day). fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits. in a pre- and post-natal development study in pregnant rats dosed by the subcutaneous route from late gestation through delivery and lactation (gestation day 17 to postpartum day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to 0.5 times the mrhdid (on a mcg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day). salmeterol: in 3 embryofetal development studies, pregnant rabbits received oral administration of salmeterol at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis. in pregnant dutch rabbits administered salmeterol doses approximately 50 times the mrhdid (on an auc basis at maternal oral doses of 1,000 mcg/kg/day and higher), fetal toxic effects were observed characteristically resulting from beta-adrenoceptor stimulation. these included precocious eyelid openings, cleft palate, sternebral fusion, limb and paw flexures, and delayed ossification of the frontal cranial bones. no such effects occurred at a salmeterol dose approximately 20 times the mrhdid (on an auc basis at a maternal oral dose of 600 mcg/kg/day). new zealand white rabbits were less sensitive since only delayed ossification of the frontal cranial bones was seen at a salmeterol dose approximately 2,000 times the mrhdid (on a mcg/m2 basis at a maternal oral dose of 10,000 mcg/kg/day). in 2 embryofetal development studies, pregnant rats received salmeterol by oral administration at doses ranging from 100 to 10,000 mcg/kg/day during the period of organogenesis. salmeterol produced no maternal toxicity or embryofetal effects at doses up to 973 times the mrhdid (on a mcg/m2 basis at maternal oral doses up to 10,000 mcg/kg/day). in a peri- and post-natal development study in pregnant rats dosed by the oral route from late gestation through delivery and lactation, salmeterol at a dose 973 times the mrhdid (on a mcg/m2 basis with a maternal oral dose of 10,000 mcg/kg/day) was fetotoxic and decreased the fertility of survivors. salmeterol xinafoate crossed the placenta following oral administration to mice and rats. risk summary there are no available data on the presence of fluticasone propionate or salmeterol in human milk, the effects on the breastfed child, or the effects on milk production. other corticosteroids have been detected in human milk. however, fluticasone propionate and salmeterol concentrations in plasma after inhaled therapeutic doses are low and therefore concentrations in human breast milk are likely to be correspondingly low [see clinical pharmacology (12.3)] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluticasone propionate and salmeterol inhalation powder and any potential adverse effects on the breastfed child from fluticasone propionate and salmeterol inhalation powder or from the underlying maternal condition. data animal data: subcutaneous administration of tritiated fluticasone propionate at a dose of 10 mcg/kg/day to lactating rats resulted in measurable levels in milk. oral administration of salmeterol at a dose of 10,000 mcg/kg/day to lactating rats resulted in measurable levels in milk. use of fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg in patients aged 4 to 11 years is supported by extrapolation of efficacy data from older subjects and by safety and efficacy data from a trial of fluticasone propionate and salmeterol inhalation powder 100 mcg/50 mcg in children with asthma aged 4 to 11 years [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.1)] . the safety and effectiveness of fluticasone propionate and salmeterol inhalation powder in children with asthma younger than 4 years have not been established. ics, including fluticasone propionate, a component of fluticasone propionate and salmeterol inhalation powder, may cause a reduction in growth velocity in children and adolescents [see warnings and precautions (5.14)] . the growth of pediatric patients receiving orally inhaled corticosteroids, including fluticasone propionate and salmeterol inhalation powder, should be monitored. a 52-week placebo-controlled trial to assess the potential growth effects of fluticasone propionate inhalation powder (flovent rotadisk) at 50 and 100 mcg twice daily was conducted in the u.s. in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years. the mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50-mcg group (n = 98), and 5.66 cm/year in the 100-mcg group (n = 89). an imbalance in the proportion of children entering puberty between groups and a higher dropout rate in the placebo group due to poorly controlled asthma may be confounding factors in interpreting these data. a separate subset analysis of children who remained prepubertal during the trial revealed growth rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mcg group (n = 74), and 5.67 cm/year in the 100-mcg group (n = 79). in children aged 8.5 years, the mean age of children in this trial, the range for expected growth velocity is: boys – 3rd percentile = 3.8 cm/year, 50th percentile = 5.4 cm/year, and 97th percentile = 7.0 cm/year; girls – 3rd percentile = 4.2 cm/year, 50th percentile = 5.7 cm/year, and 97th percentile = 7.3 cm/year. the clinical relevance of these growth data is not certain. if a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect of corticosteroids should be considered. the potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained. to minimize the systemic effects of orally inhaled corticosteroids, including fluticasone propionate and salmeterol inhalation powder, each patient should be titrated to the lowest strength that effectively controls his/her asthma [see dosage and administration (2.1)] . clinical trials of fluticasone propionate and salmeterol inhalation powder for asthma did not include sufficient numbers of subjects aged 65 years and older to determine whether older subjects with asthma respond differently than younger subjects. of the total number of subjects in clinical trials receiving fluticasone propionate and salmeterol inhalation powder for copd, 1,621 were aged 65 years and older and 379 were aged 75 years and older. subjects with copd aged 65 years and older had a higher incidence of serious adverse events compared with subjects younger than 65 years. although the distribution of adverse events was similar in the 2 age groups, subjects older than 65 years experienced more severe events. in two 1-year trials, the excess risk of pneumonia that was seen in subjects treated with fluticasone propionate and salmeterol inhalation powder compared with those treated with salmeterol was greater in subjects older than 65 years than in subjects younger than 65 years [see adverse reactions (6.2)] . as with other products containing beta2 -agonists, special caution should be observed when using fluticasone propionate and salmeterol inhalation powder in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta2 -agonists. based on available data for fluticasone propionate and salmeterol inhalation powder or its active components, no adjustment of dosage of fluticasone propionate and salmeterol inhalation powder in geriatric patients is warranted. no relationship between fluticasone propionate systemic exposure and age was observed in 57 subjects with copd (aged 40 to 82 years) given 250 or 500 mcg twice daily. formal pharmacokinetic studies using fluticasone propionate and salmeterol inhalation powder have not been conducted in patients with hepatic impairment. however, since both fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma. therefore, patients with hepatic disease should be closely monitored. formal pharmacokinetic studies using fluticasone propionate and salmeterol inhalation powder have not been conducted in patients with renal impairment. instructions for use fluticasone propionate and salmeterol inhalation powder (floo tik’ a sone proe’ pee oh nate and sal mee’ ter ol) for oral inhalation rx only read this instructions for use before you start using fluticasone propionate and salmeterol inhalation powder and each time you get a refill. there may be new information. this information does not take the place of talking to your healthcare provider about your medical condition or treatment. your fluticasone propionate and salmeterol inhalation powder inhaler figure a important information about your fluticasone propionate and salmeterol inhalation powder inhaler: how to use your fluticasone propionate and salmeterol inhalation powder inhaler follow these steps every time you use fluticasone propionate and salmeterol inhalation powder. step 1. open your fluticasone propionate and salmeterol inhalation powder. step 2. slide the lever until you hear it click. figure b figure c follow the instructions below so you will not accidentally waste a dose: step 3. inhale your medicine. figure d figure e step 4. close the inhaler. figure f step 5. rinse your mouth. figure g when should you get a refill? the counter on top of the inhaler shows you how many doses are left. after you have taken 55 doses, the numbers 5 to 0 will show in red. see figure h. these numbers warn you there are only a few doses left and are a reminder to get a refill. figure h for correct use of the inhaler, remember: for more information about fluticasone propionate and salmeterol inhalation powder or how to use your inhaler, call hikma pharmaceuticals usa inc. at 1-800-962-8364. the brands listed are trademarks of their respective owners. this instructions for use has been approved by the u.s. food and drug administration distributed by: hikma pharmaceuticals usa inc. berkeley heights, nj 07922 c50001155/02 revised september 2022

Egyesült Államok - angol - NLM (National Library of Medicine)

teva pharmaceuticals usa, inc. - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u), salmeterol xinafoate (unii: 6ew8q962a5) (salmeterol - unii:2i4bc502bt) - fluticasone propionate and salmeterol inhalation powder is indicated for the twice-daily treatment of asthma in patients aged 4 years and older. fluticasone propionate and salmeterol inhalation powder should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta2 -adrenergic agonist (laba). important limitation of use fluticasone propionate and salmeterol inhalation powder is not indicated for the relief of acute bronchospasm. fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg is indicated for the twice-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (copd), including chronic bronchitis and/or emphysema. fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg is also indicated to reduce exacerbations of copd in patients with a history of exacerbations. flut

Egyesült Államok - angol - NLM (National Library of Medicine)

prasco laboratories - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u), salmeterol xinafoate (unii: 6ew8q962a5) (salmeterol - unii:2i4bc502bt) - fluticasone propionate and salmeterol hfa is indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. fluticasone propionate and salmeterol hfa should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta2 -adrenergic agonist (laba). limitations of use fluticasone propionate and salmeterol hfa is not indicated for the relief of acute bronchospasm. fluticasone propionate and salmeterol hfa is contraindicated in the following conditions: risk summary there are insufficient data on the use of fluticasone propionate and salmeterol hfa or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. there are clinical considerations with the use of fluticasone propionate and salmeterol hfa in pregnant women. (see clinical considerations.) in animals, teratogenicity characteristic of cortic

Egyesült Államok - angol - NLM (National Library of Medicine)

preferred pharmaceuticals inc. - salmeterol xinafoate (unii: 6ew8q962a5) (salmeterol - unii:2i4bc502bt), fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u) - fluticasone propionate and salmeterol inhalation powder is indicated for the twice-daily treatment of asthma in patients aged 4 years and older. fluticasone propionate and salmeterol inhalation powder should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ics) or whose disease warrants initiation of treatment with both an ics and long-acting beta2 -adrenergic agonist (laba). important limitation of use fluticasone propionate and salmeterol inhalation powder is not indicated for the relief of acute bronchospasm. fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg is indicated for the twice-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (copd), including chronic bronchitis and/or emphysema. fluticasone propionate and salmeterol inhalation powder 250 mcg/50 mcg is also indicated to reduce exacerbations of copd in patients with a history of exacerbations. flutica

Egyesült Államok - angol - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - glycopyrrolate (unii: v92so9wp2i) (glycopyrronium - unii:a14fb57v1d), formoterol fumarate (unii: w34shf8j2k) (formoterol - unii:5zz84gcw8b) - glycopyrrolate 9 ug - bevespi aerosphere is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (copd). limitations of use: bevespi aerosphere is not indicated for the relief of acute bronchospasm or for the treatment of asthma [see warnings and precautions (5.1, 5.2)] . bevespi aerosphere is contraindicated in: risk summary   there are no adequate and well-controlled trials of bevespi aerosphere or its individual components, glycopyrrolate and formoterol fumarate, in pregnant women to inform a drug-associated risk. in animal reproduction studies, glycopyrrolate alone, administered by the subcutaneous route in rats and rabbits, did not cause structural abnormalities or affect fetal survival at exposures approximately 2700 and 5400 times from the maximum recommended human daily inhalation dose (mrhdid), respectively. glycopyrrolate had no effects on the physical, functional, and behavioral development of rat pups with exposures up to 2700 times the mrhdid. formoterol fumarate alone, admin

Egyesült Államok - angol - NLM (National Library of Medicine)

glaxosmithkline llc - umeclidinium bromide (unii: 7an603v4jv) (umeclidinium - unii:ge2t1418sv), vilanterol trifenatate (unii: 40aho2c6dg) (vilanterol - unii:028lzy775b) - umeclidinium 62.5 ug - anoro ellipta is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (copd). limitations of use anoro ellipta is not indicated for the relief of acute bronchospasm or for the treatment of asthma. the safety and effectiveness of anoro ellipta in asthma have not been established. anoro ellipta is contraindicated in: risk summary there are insufficient data on the use of anoro ellipta or its individual components, umeclidinium and vilanterol, in pregnant women to inform a drug-associated risk. (see clinical considerations.) in animal reproduction studies, umeclidinium administered via inhalation or subcutaneously to pregnant rats and rabbits was not associated with adverse effects on embryofetal development at exposures approximately 50 and 200 times, respectively, the human exposure at the maximum recommended human daily inhaled dose (mrhdid). vilanterol administered via inhalation to pregnant rats and rabbits produced no fetal structural abnormalities at exposures approximately 70 times the mrhdid. (see data.) the estimated risk of major birth defects and miscarriage for the indicated populations is unknown. in the u.s. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations labor or delivery: anoro ellipta should be used during late gestation and labor only if the potential benefit justifies the potential for risks related to beta-agonists interfering with uterine contractility. data animal data: the combination of umeclidinium and vilanterol has not been studied in pregnant animals. studies in pregnant animals have been conducted with umeclidinium and vilanterol individually. umeclidinium: in separate embryofetal developmental studies, pregnant rats and rabbits received umeclidinium during the period of organogenesis at doses up to approximately 50 and 200 times the mrhdid, respectively (on an auc basis at maternal inhalation doses up to 278 mcg/kg/day in rats and at maternal subcutaneous doses up to 180 mcg/kg/day in rabbits). no evidence of teratogenic effects was observed in either species. in a perinatal and postnatal developmental study in rats, dams received umeclidinium during late gestation and lactation periods with no evidence of effects on offspring development at doses up to approximately 26 times the mrhdid (on an auc basis at maternal subcutaneous doses up to 60 mcg/kg/day). vilanterol: in separate embryofetal developmental studies, pregnant rats and rabbits received vilanterol during the period of organogenesis at doses up to approximately 13,000 and 450 times, respectively, the mrhdid (on a mcg/m2 basis at maternal inhalation doses up to 33,700 mcg/kg/day in rats and on an auc basis at maternal inhaled doses up to 5,740 mcg/kg/day in rabbits). no evidence of structural abnormalities was observed at any dose in rats or in rabbits up to approximately 70 times the mrhdid (on an auc basis at maternal doses up to 591 mcg/kg/day in rabbits). however, fetal skeletal variations were observed in rabbits at approximately 450 times the mrhdid (on an auc basis at maternal inhaled or subcutaneous doses of 5,740 or 300 mcg/kg/day, respectively). the skeletal variations included decreased or absent ossification in cervical vertebral centrum and metacarpals. in a perinatal and postnatal developmental study in rats, dams received vilanterol during late gestation and the lactation periods at doses up to approximately 3,900 times the mrhdid (on a mcg/m2 basis at maternal oral doses up to 10,000 mcg/kg/day). no evidence of effects in offspring development was observed. risk summary there is no information available on the presence of umeclidinium or vilanterol in human milk, the effects on the breastfed child, or the effects on milk production. umeclidinium was detected in the plasma of offspring of lactating rats treated with umeclidinium suggesting its presence in maternal milk. (see data.) the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for anoro ellipta and any potential adverse effects on the breastfed child from umeclidinium or vilanterol or from the underlying maternal condition. data subcutaneous administration of umeclidinium to lactating rats at greater than or equal to 60 mcg/kg/day resulted in a quantifiable level of umeclidinium in 2 of 54 pups, which may indicate transfer of umeclidinium in rat milk. the safety and effectiveness of anoro ellipta have not been established in pediatric patients. anoro ellipta is not indicated for use in pediatric patients. based on available data, no adjustment of the dosage of anoro ellipta in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. clinical trials of anoro ellipta for copd included 2,143 subjects aged 65 years and older and 478 subjects aged 75 years and older. 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 subjects. patients with moderate hepatic impairment (child-pugh score of 7-9) showed no relevant increases in cmax or auc, nor did protein binding differ between subjects with moderate hepatic impairment and their healthy controls. studies in subjects with severe hepatic impairment have not been performed [see clinical pharmacology (12.3)] . there were no significant increases in either umeclidinium or vilanterol exposure in subjects with severe renal impairment (crcl <30 ml/min) compared with healthy subjects. no dosage adjustment is required in patients with renal impairment [see clinical pharmacology (12.3)] .