United States - English - 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)] .

United States - English - NLM (National Library of Medicine)

glaxosmithkline llc - umeclidinium bromide (unii: 7an603v4jv) (umeclidinium - unii:ge2t1418sv) - umeclidinium 62.5 ug - incruse ellipta is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (copd). incruse ellipta is contraindicated in the following conditions: risk summary there are insufficient data on the use of umeclidinium in pregnant women to inform a drug‑associated risk. umeclidinium administered via inhalation or subcutaneously to pregnant rats and rabbits was not associated with adverse effect on embryofetal development at exposures approximately 50 and 200 times, respectively, the human exposure at the maximum recommended human daily inhaled dose (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. data animal data: 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). risk summary there is no information available on the presence of umeclidinium 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 incruse ellipta and any potential adverse effects on the breastfed child from umeclidinium 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 milk. the safety and effectiveness of incruse ellipta have not been established in pediatric patients. incruse ellipta is not indicated for use in pediatric patients. based on available data, no adjustment of the dosage of incruse ellipta in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. clinical trials of incruse ellipta included 810 subjects aged 65 years and older, and, of those, 183 subjects were 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)] . patients with severe renal impairment (crcl <30 ml/min) showed no relevant increases in cmax or auc, nor did protein binding differ between subjects with severe renal impairment and their healthy controls. no dosage adjustment is required in patients with renal impairment [see clinical pharmacology (12.3)] . instructions for use incruse ellipta (in-cruise e-lip-ta) (umeclidinium inhalation powder) for oral inhalation use read this before you start: your incruse ellipta inhaler how to use your inhaler figure a figure b important notes: check the counter. see figure c. figure c prepare your dose: wait to open the cover until you are ready to take your dose. figure d step 1. open the cover of the inhaler. see figure d. figure e step 2. breathe out. see figure e. figure f step 3. inhale your medicine. see figure f. figure g figure h figure i step 4. breathe out slowly and gently. see figure i. figure j step 5. close the inhaler. see figure j. important note: when should you get a refill? figure k for more information about incruse ellipta or how to use your inhaler, call 1-888-825-5249. trademarks are owned by or licensed to the gsk group of companies. glaxosmithkline, durham, nc 27701 ©2023 gsk group of companies or its licensor. inc:3ifu this instructions for use has been approved by the u.s. food and drug administration               revised: december 2023

United States - English - NLM (National Library of Medicine)

glaxosmithkline llc - fluticasone furoate (unii: js86977wnv) (fluticasone - unii:cut2w21n7u), umeclidinium bromide (unii: 7an603v4jv) (umeclidinium - unii:ge2t1418sv), vilanterol trifenatate (unii: 40aho2c6dg) (vilanterol - unii:028lzy775b) - fluticasone furoate 100 ug - trelegy ellipta is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (copd). trelegy ellipta is indicated for the maintenance treatment of asthma in patients aged 18 years and older. trelegy ellipta is not indicated for the relief of acute bronchospasm. trelegy ellipta is contraindicated in the following conditions: risk summary there are insufficient data on the use of trelegy ellipta or its individual components, fluticasone furoate, umeclidinium, and vilanterol, in pregnant women to inform a drug‑associated risk. (see clinical considerations.) in an animal reproduction study, fluticasone furoate and vilanterol administered by inhalation alone or in combination to pregnant rats during the period of organogenesis produced no fetal structural abnormalities. the highest fluticasone furoate and vilanterol doses in this study were approximately 4.5 and 40 times the maximum recommended human daily inhalation doses (mrhdid) of 200 and 25 mcg, respectively in adults. (see data.) umeclidinium administered via inhalation or subcutaneously to pregnant rats and rabbits was not associated with adverse effect on embryofetal development at exposures approximately 40 and 150 times, respectively, the human exposure at the mrhdid of 62.5 mcg. (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 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 or delivery: trelegy 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 fluticasone furoate, umeclidinium, and vilanterol has not been studied in pregnant animals. studies in pregnant animals have been conducted with fluticasone furoate and vilanterol in combination and individually with fluticasone furoate, umeclidinium, or vilanterol. fluticasone furoate and vilanterol: in an embryofetal developmental study, pregnant rats received fluticasone furoate and vilanterol during the period of organogenesis at doses up to approximately 4.5 and 40 times the mrhdid of 200 and 25 mcg, respectively, alone or in combination (on a mcg/m2 basis at inhalation doses up to approximately 95 mcg/kg/day). no evidence of structural abnormalities was observed. fluticasone furoate: in 2 separate embryofetal developmental studies, pregnant rats and rabbits received fluticasone furoate during the period of organogenesis at doses up to approximately 4.5 times and equal to, respectively, the mrhdid of 200 mcg (on a mcg/m2 basis at maternal inhalation doses up to 91 and 8 mcg/kg/day, respectively). no evidence of structural abnormalities in fetuses was observed in either species. in a perinatal and postnatal developmental study in rats, dams received fluticasone furoate during late gestation and lactation periods at doses up to approximately 1.5 times the mrhdid of 200 mcg (on a mcg/m2 basis at maternal inhalation doses up to 27 mcg/kg/day). no evidence of effects on offspring development was observed. umeclidinium: in 2 separate embryofetal developmental studies, pregnant rats and rabbits received umeclidinium during the period of organogenesis at doses up to approximately 40 and 150 times, respectively the mrhdid of 62.5 mcg (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 at doses up to approximately 20 times the mrhdid (on an auc basis at maternal subcutaneous doses up to 60 mcg/kg/day). no evidence of effects on offspring development was observed. vilanterol: in 2 separate embryofetal developmental studies, pregnant rats and rabbits received vilanterol during the period of organogenesis at doses up to approximately 13,000 and 760 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 120 times the mrhdid (on an auc basis at maternal doses up to 591 mcg/kg/day). however, fetal skeletal variations were observed in rabbits at approximately 760 or 840 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 fluticasone furoate, 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 trelegy ellipta and any potential adverse effects on the breastfed child from fluticasone furoate, 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 trelegy ellipta have not been established in pediatric patients (aged 17 years and younger). trelegy ellipta is not indicated for use in pediatric patients. effects on growth orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children and adolescents. controlled clinical trials have shown that ics may cause a reduction in growth in children. in these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appears to be related to dose and duration of exposure. this effect has been 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 children 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. a randomized, double-blind, parallel-group, multicenter, 1-year, placebo-controlled trial evaluated the effect of once-daily treatment with 110 mcg of fluticasone furoate in the nasal spray formulation on growth velocity assessed by stadiometry. the subjects were 474 prepubescent children (girls aged 5 to 7.5 years and boys aged 5 to 8.5 years). mean growth velocity over the 52-week treatment period was lower in the subjects receiving fluticasone furoate nasal spray (5.19 cm/year) compared with placebo (5.46 cm/year). the mean reduction in growth velocity was 0.27 cm/year (95% ci: 0.06, 0.48) [see warnings and precautions (5.18)] . based on available data, no adjustment of the dosage of trelegy ellipta in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. in copd trials 1 and 2 (coadministration trials), 189 subjects aged 65 years and older, of which 39 subjects were aged 75 years and older, were administered umeclidinium 62.5 mcg + fluticasone furoate/vilanterol 100/25 mcg. in copd trial 3, 2,265 subjects aged 65 years and older, of which 565 subjects were aged 75 years and older, were administered trelegy ellipta. in an asthma clinical trial (trial 4), 159 subjects aged 65 years and older, of which 27 subjects were aged 75 years and older, were administered trelegy ellipta 100/62.5/25 mcg or trelegy ellipta 200/62.5/25 mcg. 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. trelegy ellipta has not been studied in subjects with hepatic impairment. information on the individual components is provided below. fluticasone furoate/vilanterol fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment compared with healthy subjects. hepatic impairment had no effect on vilanterol systemic exposure. use trelegy ellipta with caution in patients with moderate or severe hepatic impairment. monitor patients for corticosteroid-related side effects [see clinical pharmacology (12.3)] . umeclidinium 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)] . trelegy ellipta has not been studied in subjects with renal impairment. information on the individual components is provided below. fluticasone furoate/vilanterol there were no significant increases in either fluticasone furoate 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)] . umeclidinium patients with severe renal impairment (crcl <30 ml/min) showed no relevant increases in cmax or auc, nor did protein binding differ between subjects with severe renal impairment and their healthy controls. no dosage adjustment is required in patients with renal impairment [see clinical pharmacology (12.3)] .

New Zealand - English - Medsafe (Medicines Safety Authority)

glaxosmithkline nz limited - umeclidinium bromide 74.2ug equivalent to umeclidinium 62.5 mcg;  ; vilanterol trifenatate 40ug equivalent to vilanterol 25 mcg;   - powder for inhalation - 62.5mcg/25mcg - active: umeclidinium bromide 74.2ug equivalent to umeclidinium 62.5 mcg   vilanterol trifenatate 40ug equivalent to vilanterol 25 mcg   excipient: lactose monohydrate magnesium stearate - long-term once daily maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (copd).

European Union - English - EMA (European Medicines Agency)

glaxosmithkline (ireland) limited - umeclidinium bromide, vilanterol - pulmonary disease, chronic obstructive - drugs for obstructive airway diseases, - laventair ellipta is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (copd).

European Union - English - EMA (European Medicines Agency)

glaxosmithkline (ireland) limited - umeclidinium bromide, vilanterol trifenatate - pulmonary disease, chronic obstructive - drugs for obstructive airway diseases, - anoro ellipta is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (copd).

European Union - English - EMA (European Medicines Agency)

glaxosmithkline (ireland) limited - umeclidinium bromide - pulmonary disease, chronic obstructive - drugs for obstructive airway diseases, - indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (copd).,

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

ennogen healthcare ltd - vilanterol trifenatate; umeclidinium bromide - inhalation powder - 22microgram/1dose ; 65microgram/1dose

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

j m mcgill ltd - vilanterol trifenatate; umeclidinium bromide - inhalation powder - 22microgram/1dose ; 65microgram/1dose

European Union - English - EMA (European Medicines Agency)

glaxosmithkline trading services limited - umeclidinium bromide - pulmonary disease, chronic obstructive - drugs for obstructive airway diseases, - rolufta is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (copd).,