Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

cosette pharmaceuticals, inc. - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u) - fluticasone propionate 0.05 mg in 1 g - fluticasone propionate ointment, usp 0.005% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adult patients. fluticasone propionate ointment, 0.005% is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation. pregnancy category c there are no adequate and well-controlled studies in pregnant women. therefore, fluticasone propionate ointment, 0.005% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. systemic embryofetal development studies were conducted in mice, rats and rabbits. subcutaneous doses of 15, 45 and 150 μg/kg/day of fluticasone propionate were administered to pregnant female mice from gestation days 6 to 15. a teratogenic effect characteristic of corticosteroids (cleft palate) was noted after administration of 45 and 150 μg/kg/day (less than the mrhd in adults based on body surface area comparisons) in

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

prasco laboratories - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u) - fluticasone propionate hfa is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients aged 4 years and older. limitations of use fluticasone propionate hfa is not indicated for the relief of acute bronchospasm. fluticasone propionate hfa is contraindicated in the following conditions: risk summary there are insufficient data on the use of fluticasone propionate hfa in pregnant women. there are clinical considerations with the use of fluticasone propionate hfa 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, was 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 terat

Kanada - engleski - Health Canada

pharmascience inc - fluticasone propionate; salmeterol (salmeterol xinafoate) - powder - 100mcg; 50mcg - fluticasone propionate 100mcg; salmeterol (salmeterol xinafoate) 50mcg - adrenals

Kanada - engleski - Health Canada

pharmascience inc - fluticasone propionate; salmeterol (salmeterol xinafoate) - powder - 250mcg; 50mcg - fluticasone propionate 250mcg; salmeterol (salmeterol xinafoate) 50mcg - adrenals

Kanada - engleski - Health Canada

pharmascience inc - fluticasone propionate; salmeterol (salmeterol xinafoate) - powder - 500mcg; 50mcg - fluticasone propionate 500mcg; salmeterol (salmeterol xinafoate) 50mcg - adrenals

Sjedinjene Američke Države - engleski - 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

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

a-s medication solutions - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u) - fluticasone propionate hfa is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients aged 4 years and older. limitations of use fluticasone propionate hfa is not indicated for the relief of acute bronchospasm. fluticasone propionate hfa is contraindicated in the following conditions: risk summary there are insufficient data on the use of fluticasone propionate hfa in pregnant women. there are clinical considerations with the use of fluticasone propionate hfa 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, was 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. 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 with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. data human data: following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery. animal data: 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 0.5 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). the rat no observed adverse effect level (noael) was observed at approximately 0.17 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 0.1 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 0.04 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 0.14 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 0.03 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 0.006 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 0.04 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 0.001 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 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 0.3 times the mrhdid (on a mcg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day). risk summary there are no available data on the presence of fluticasone propionate 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 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 hfa and any potential adverse effects on the breastfed child from fluticasone propionate hfa 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. the safety and effectiveness of fluticasone propionate hfa in pediatric patients aged 4 years and older have been established [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2)] . use of fluticasone propionate hfa in patients aged 4 to 11 years is supported by evidence from adequate and well-controlled trials in adults and adolescents aged 12 years and older, pharmacokinetic trials in patients aged 4 to 11 years, established efficacy of fluticasone propionate formulated as flovent diskus (fluticasone propionate inhalation powder) and flovent rotadisk (fluticasone propionate inhalation powder) in patients aged 4 to 11 years, and supportive findings with fluticasone propionate hfa in a trial conducted in subjects aged 4 to 11 years. the safety and effectiveness of fluticasone propionate hfa in pediatric patients younger than 4 years have not been established. effects on growth orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. a reduction of growth velocity in children or teenagers may occur as a result of poorly controlled asthma or from use of corticosteroids including ics. the effects of long-term treatment of children and adolescents with ics, including fluticasone propionate, on final adult height are not known. controlled clinical trials have shown that ics may cause a reduction in growth in pediatric patients. in these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appeared to depend upon dose and duration of exposure. this effect was observed in the absence of laboratory evidence of hpa axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of hpa axis function. the long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. the potential for “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. the effects on growth velocity of treatment with orally inhaled corticosteroids for over 1 year, including the impact on final adult height, are unknown. the growth of children and adolescents receiving orally inhaled corticosteroids, including fluticasone propionate hfa, should be monitored routinely (e.g., via stadiometry). the potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. to minimize the systemic effects of orally inhaled corticosteroids, including fluticasone propionate hfa, each patient should be titrated to the lowest dose that effectively controls his/her symptoms. since a cross trial comparison in adult and adolescent subjects (aged 12 years and older) indicated that systemic exposure of inhaled fluticasone propionate from fluticasone propionate hfa would be higher than exposure from flovent rotadisk, results from a trial to assess the potential growth effects of flovent rotadisk in pediatric subjects (aged 4 to 11 years) are provided. 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. pediatric patients younger than 4 years pharmacokinetics: [see clinical pharmacology (12.3)] . pharmacodynamics: a 12-week, double-blind, placebo-controlled, parallel-group trial was conducted in children with asthma aged 1 to younger than 4 years. twelve-hour overnight urinary cortisol excretion after a 12-week treatment period with 88 mcg of fluticasone propionate hfa twice daily (n = 73) and with placebo (n = 42) were calculated. the mean and median change from baseline in urine cortisol over 12 hours were -0.7 and 0.0 mcg for fluticasone propionate hfa and 0.3 and -0.2 mcg for placebo, respectively. in a 1-way crossover trial in children aged 6 to younger than 12 months with reactive airways disease (n = 21), serum cortisol was measured over a 12-hour dosing period. subjects received placebo treatment for a 2-week period followed by a 4-week treatment period with 88 mcg of fluticasone propionate hfa twice daily with an aerochamber plus valved holding chamber (vhc) with mask. the geometric mean ratio of serum cortisol over 12 hours [auc(0-12 h) ] following fluticasone propionate hfa (n = 16) versus placebo (n = 18) was 0.95 (95% ci: 0.72, 1.27). safety: fluticasone propionate hfa administered as 88 mcg twice daily was evaluated for safety in 239 pediatric subjects aged 1 to younger than 4 years in a 12-week, double-blind, placebo-controlled trial. treatments were administered with an aerochamber plus vhc with mask. the following events occurred with a frequency >3% and more frequently in subjects receiving fluticasone propionate hfa than in subjects receiving placebo, regardless of causality assessment: pyrexia, nasopharyngitis, upper respiratory tract infection, vomiting, otitis media, diarrhea, bronchitis, pharyngitis, and viral infection. fluticasone propionate hfa administered as 88 mcg twice daily was evaluated for safety in 23 pediatric subjects aged 6 to 12 months in an open-label placebo-controlled trial. treatments were administered with an aerochamber plus vhc with mask for 2 weeks with placebo followed by 4 weeks with active drug. there was no discernable difference in the types of adverse events reported between subjects receiving placebo compared with the active drug. in vitro testing of dose delivery with holding chambers: in vitro dose characterization studies were performed to evaluate the delivery of fluticasone propionate hfa via holding chambers with attached masks. the studies were conducted with 2 different holding chambers (aerochamber plus vhc and aerochamber z-stat plus vhc) with masks (small and medium size) at inspiratory flow rates of 4.9, 8.0, and 12.0 l/min in combination with holding times of 0, 2, 5, and 10 seconds. the flow rates were selected to be representative of inspiratory flow rates of children aged 6 to 12 months, 2 to 5 years, and over 5 years, respectively. the mean delivered dose of fluticasone propionate through the holding chambers with masks was lower than the 44 mcg of fluticasone propionate delivered directly from the actuator mouthpiece. the results were similar through both holding chambers (see table 2 for data for the aerochamber plus vhc). the fine particle fraction (approximately 1 to 5 μm) across the flow rates used in these studies was 70% to 84% of the delivered dose, consistent with the removal of the coarser fraction by the holding chamber. in contrast, the fine particle fraction for fluticasone propionate hfa delivered without a holding chamber typically represents 42% to 55% of the delivered dose measured at the standard flow rate of 28.3 l/min. these data suggest that, on a per kilogram basis, young children receive a comparable dose of fluticasone propionate when delivered via a holding chamber and mask as adults do without their use. age mask flow rate (l/min) holding time (seconds) mean medication delivery through aerochamber plus valved holding chamber (mcg/actuation) body weight 50th percentile (kg)a medication delivered per actuation (mcg/kg)b 6 to 12 months small 4.9 2 5 10 8.3 6.7 7.5 7.5 7.5-9.9 0.8-1.1 0.7-0.9 0.8-1.0 0.8-1.0 2 to 5 years small 8.0 2 5 10 7.3 6.8 6.7 7.7 12.3-18.0 0.4-0.6 0.4-0.6 0.4-0.5 0.4-0.6 2 to 5 years medium 8.0 2 5 10 7.8 7.7 8.1 9.0 12.3-18.0 0.4-0.6 0.4-0.6 0.5-0.7 0.5-0.7 >5 years medium 12.0 2 5 10 12.3 11.8 12.0 10.1 18.0 0.7 0.7 0.7 0.6 of the total number of subjects treated with fluticasone propionate hfa in u.s. and non-u.s. clinical trials, 173 were aged 65 years or older, 19 of which were 75 years or 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, but greater sensitivity of some older individuals cannot be ruled out. formal pharmacokinetic studies using fluticasone propionate hfa have not been conducted in patients with hepatic impairment. since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. therefore, patients with hepatic disease should be closely monitored. formal pharmacokinetic studies using fluticasone propionate hfa have not been conducted in patients with renal impairment.

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

a-s medication solutions - fluticasone propionate (unii: o2gmz0lf5w) (fluticasone - unii:cut2w21n7u) - fluticasone propionate hfa is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients aged 4 years and older. limitations of use fluticasone propionate hfa is not indicated for the relief of acute bronchospasm. fluticasone propionate hfa is contraindicated in the following conditions: risk summary there are insufficient data on the use of fluticasone propionate hfa in pregnant women. there are clinical considerations with the use of fluticasone propionate hfa 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, was 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. 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 with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. data human data: following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery. animal data: 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 0.5 times the mrhdid (on a mcg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). the rat no observed adverse effect level (noael) was observed at approximately 0.17 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 0.1 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 0.04 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 0.14 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 0.03 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 0.006 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 0.04 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 0.001 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 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 0.3 times the mrhdid (on a mcg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day). risk summary there are no available data on the presence of fluticasone propionate 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 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 hfa and any potential adverse effects on the breastfed child from fluticasone propionate hfa 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. the safety and effectiveness of fluticasone propionate hfa in pediatric patients aged 4 years and older have been established [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2)] . use of fluticasone propionate hfa in patients aged 4 to 11 years is supported by evidence from adequate and well-controlled trials in adults and adolescents aged 12 years and older, pharmacokinetic trials in patients aged 4 to 11 years, established efficacy of fluticasone propionate formulated as flovent diskus (fluticasone propionate inhalation powder) and flovent rotadisk (fluticasone propionate inhalation powder) in patients aged 4 to 11 years, and supportive findings with fluticasone propionate hfa in a trial conducted in subjects aged 4 to 11 years. the safety and effectiveness of fluticasone propionate hfa in pediatric patients younger than 4 years have not been established. effects on growth orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. a reduction of growth velocity in children or teenagers may occur as a result of poorly controlled asthma or from use of corticosteroids including ics. the effects of long-term treatment of children and adolescents with ics, including fluticasone propionate, on final adult height are not known. controlled clinical trials have shown that ics may cause a reduction in growth in pediatric patients. in these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appeared to depend upon dose and duration of exposure. this effect was observed in the absence of laboratory evidence of hpa axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of hpa axis function. the long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. the potential for “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. the effects on growth velocity of treatment with orally inhaled corticosteroids for over 1 year, including the impact on final adult height, are unknown. the growth of children and adolescents receiving orally inhaled corticosteroids, including fluticasone propionate hfa, should be monitored routinely (e.g., via stadiometry). the potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. to minimize the systemic effects of orally inhaled corticosteroids, including fluticasone propionate hfa, each patient should be titrated to the lowest dose that effectively controls his/her symptoms. since a cross trial comparison in adult and adolescent subjects (aged 12 years and older) indicated that systemic exposure of inhaled fluticasone propionate from fluticasone propionate hfa would be higher than exposure from flovent rotadisk, results from a trial to assess the potential growth effects of flovent rotadisk in pediatric subjects (aged 4 to 11 years) are provided. 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. pediatric patients younger than 4 years pharmacokinetics: [see clinical pharmacology (12.3)] . pharmacodynamics: a 12-week, double-blind, placebo-controlled, parallel-group trial was conducted in children with asthma aged 1 to younger than 4 years. twelve-hour overnight urinary cortisol excretion after a 12-week treatment period with 88 mcg of fluticasone propionate hfa twice daily (n = 73) and with placebo (n = 42) were calculated. the mean and median change from baseline in urine cortisol over 12 hours were -0.7 and 0.0 mcg for fluticasone propionate hfa and 0.3 and -0.2 mcg for placebo, respectively. in a 1-way crossover trial in children aged 6 to younger than 12 months with reactive airways disease (n = 21), serum cortisol was measured over a 12-hour dosing period. subjects received placebo treatment for a 2-week period followed by a 4-week treatment period with 88 mcg of fluticasone propionate hfa twice daily with an aerochamber plus valved holding chamber (vhc) with mask. the geometric mean ratio of serum cortisol over 12 hours [auc(0-12 h) ] following fluticasone propionate hfa (n = 16) versus placebo (n = 18) was 0.95 (95% ci: 0.72, 1.27). safety: fluticasone propionate hfa administered as 88 mcg twice daily was evaluated for safety in 239 pediatric subjects aged 1 to younger than 4 years in a 12-week, double-blind, placebo-controlled trial. treatments were administered with an aerochamber plus vhc with mask. the following events occurred with a frequency >3% and more frequently in subjects receiving fluticasone propionate hfa than in subjects receiving placebo, regardless of causality assessment: pyrexia, nasopharyngitis, upper respiratory tract infection, vomiting, otitis media, diarrhea, bronchitis, pharyngitis, and viral infection. fluticasone propionate hfa administered as 88 mcg twice daily was evaluated for safety in 23 pediatric subjects aged 6 to 12 months in an open-label placebo-controlled trial. treatments were administered with an aerochamber plus vhc with mask for 2 weeks with placebo followed by 4 weeks with active drug. there was no discernable difference in the types of adverse events reported between subjects receiving placebo compared with the active drug. in vitro testing of dose delivery with holding chambers: in vitro dose characterization studies were performed to evaluate the delivery of fluticasone propionate hfa via holding chambers with attached masks. the studies were conducted with 2 different holding chambers (aerochamber plus vhc and aerochamber z-stat plus vhc) with masks (small and medium size) at inspiratory flow rates of 4.9, 8.0, and 12.0 l/min in combination with holding times of 0, 2, 5, and 10 seconds. the flow rates were selected to be representative of inspiratory flow rates of children aged 6 to 12 months, 2 to 5 years, and over 5 years, respectively. the mean delivered dose of fluticasone propionate through the holding chambers with masks was lower than the 44 mcg of fluticasone propionate delivered directly from the actuator mouthpiece. the results were similar through both holding chambers (see table 2 for data for the aerochamber plus vhc). the fine particle fraction (approximately 1 to 5 μm) across the flow rates used in these studies was 70% to 84% of the delivered dose, consistent with the removal of the coarser fraction by the holding chamber. in contrast, the fine particle fraction for fluticasone propionate hfa delivered without a holding chamber typically represents 42% to 55% of the delivered dose measured at the standard flow rate of 28.3 l/min. these data suggest that, on a per kilogram basis, young children receive a comparable dose of fluticasone propionate when delivered via a holding chamber and mask as adults do without their use. age mask flow rate (l/min) holding time (seconds) mean medication delivery through aerochamber plus valved holding chamber (mcg/actuation) body weight 50th percentile (kg)a medication delivered per actuation (mcg/kg)b 6 to 12 months small 4.9 2 5 10 8.3 6.7 7.5 7.5 7.5-9.9 0.8-1.1 0.7-0.9 0.8-1.0 0.8-1.0 2 to 5 years small 8.0 2 5 10 7.3 6.8 6.7 7.7 12.3-18.0 0.4-0.6 0.4-0.6 0.4-0.5 0.4-0.6 2 to 5 years medium 8.0 2 5 10 7.8 7.7 8.1 9.0 12.3-18.0 0.4-0.6 0.4-0.6 0.5-0.7 0.5-0.7 >5 years medium 12.0 2 5 10 12.3 11.8 12.0 10.1 18.0 0.7 0.7 0.7 0.6 of the total number of subjects treated with fluticasone propionate hfa in u.s. and non-u.s. clinical trials, 173 were aged 65 years or older, 19 of which were 75 years or 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, but greater sensitivity of some older individuals cannot be ruled out. formal pharmacokinetic studies using fluticasone propionate hfa have not been conducted in patients with hepatic impairment. since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. therefore, patients with hepatic disease should be closely monitored. formal pharmacokinetic studies using fluticasone propionate hfa have not been conducted in patients with renal impairment.

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

a-s medication solutions - 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

Sjedinjene Američke Države - engleski - NLM (National Library of Medicine)

a-s medication solutions - 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 powder 250/50 mcg twice daily is the only approved dosage for the treatment of copd because an efficacy advantage of the higher strength fluticasone propionate/salmeterol diskus inhalation powder 500/50 mcg over fluticasone propionate/salmeterol diskus inhalation powder 250/50 mcg has not been demonstrated. important limitation of use fluticasone propionate/salmeterol diskus is not indicated for the relief of acute bronchospasm. the use of fluticasone propionate/salmeterol diskus is contraindicated in the following conditions: risk summary there are insufficient data on the use of fluticasone propionate/salmeterol diskus or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. there are clinical considerations with the use of fluticasone propionate/salmeterol diskus 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/salmeterol diskus during labor and delivery. because of the potential for beta-agonist interference with uterine contractility, use of fluticasone propionate/salmeterol diskus 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/salmeterol diskus and any potential adverse effects on the breastfed child from fluticasone propionate/salmeterol diskus 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/salmeterol diskus 100/50 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/salmeterol diskus 100/50 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/salmeterol diskus in children with asthma younger than 4 years have not been established. ics, including fluticasone propionate, a component of fluticasone propionate/salmeterol diskus, 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/salmeterol diskus, 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/salmeterol diskus, 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/salmeterol diskus 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/salmeterol diskus 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/salmeterol diskus 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/salmeterol diskus in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta2 -agonists. based on available data for fluticasone propionate/salmeterol diskus or its active components, no adjustment of dosage of fluticasone propionate/salmeterol diskus 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/salmeterol diskus 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/salmeterol diskus have not been conducted in patients with renal impairment. instructions for use fluticasone propionate/salmeterol diskus inhalation powder for oral inhalation use read this instructions for use before you start using fluticasone propionate/salmeterol diskus 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/salmeterol diskus inhaler important information about your fluticasone propionate/salmeterol diskus inhaler: how to use your fluticasone propionate/salmeterol diskus inhaler follow these steps every time you use fluticasone propionate/salmeterol diskus. step 1. open your fluticasone propionate/salmeterol diskus. step 2. slide the lever until you hear it click. 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 diskus. figure f step 5. rinse your mouth. the counter on top of the diskus 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. this instructions for use has been approved by the u.s. food and drug administration               revised: july 2023