Data from FDA - Curated by EPG Health - Last updated 13 June 2018

Indication(s)

1 INDICATIONS AND USAGE TRELEGY ELLIPTA 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. TRELEGY ELLIPTA is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations. Important Limitations of Use TRELEGY ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma. TRELEGY ELLIPTA is a combination of fluticasone furoate, an inhaled corticosteroid (ICS); umeclidinium, an anticholinergic; and vilanterol, a long-acting beta2-adrenergic agonist (LABA), indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). TRELEGY ELLIPTA is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations. (1) Important limitations of use: Not indicated for relief of acute bronchospasm or the treatment of asthma. (1, 5.2)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD)

View highlights from recent congresses presented in new expert videos with leading physicians.

+ 7 more

Allergic Rhinitis

Allergic Rhinitis

Allergic rhinitis causes great strain on the workforce. Help to reduce sick days and improve productivity with appropriate treatment options.

+ 4 more

Cystic Fibrosis Knowledge Centre

Cystic Fibrosis Knowledge Centre

View disease awareness information, treatment options and European Cystic Fibrosis Society best practice guidelines.

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS The use of TRELEGY ELLIPTA is contraindicated in patients: •with severe hypersensitivity to milk proteins. •who have demonstrated hypersensitivity to fluticasone furoate, umeclidinium, vilanterol, or any of the excipients [see Warnings and Precautions (5.11), Description (11)]. Severe hypersensitivity to milk proteins or any ingredients. (4)
Adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are described in greater detail in other sections: •Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions (5.1)] • Candida albicans infection [see Warnings and Precautions (5.4)] •Increased risk of pneumonia in COPD [see Warnings and Precautions (5.5)] •Immunosuppression [see Warnings and Precautions (5.6)] •Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8)] •Paradoxical bronchospasm [see Warnings and Precautions (5.10)] •Cardiovascular effects [see Warnings and Precautions (5.12)] •Reduction in bone mineral density [see Warnings and Precautions (5.13)] •Worsening of narrow-angle glaucoma [see Warnings and Precautions (5.14)] •Worsening of urinary retention [see Warnings and Precautions (5.15)] Most common adverse reactions (incidence ≥1%) are upper respiratory tract infection, pneumonia, bronchitis, oral candidiasis, headache, back pain, arthralgia, influenza, sinusitis, pharyngitis, rhinitis, dysgeusia, constipation, urinary tract infection, diarrhea, gastroenteritis, oropharyngeal pain, cough, and dysphonia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TRELEGY ELLIPTA is based on the safety data from two 12-week treatment trials with coadministration of umeclidinium and the fixed-dose combination of fluticasone furoate/vilanterol and a 52-week long-term trial of TRELEGY ELLIPTA compared with the fixed-dose combinations of fluticasone furoate/vilanterol and umeclidinium/vilanterol [see Clinical Studies (14)]. Trials 1 and 2 Two 12-week treatment trials (Trial 1 and Trial 2) evaluated the coadministration of umeclidinium + fluticasone furoate/vilanterol, the components of TRELEGY ELLIPTA, compared with placebo + fluticasone furoate/vilanterol. A total of 824 subjects with COPD across two 12-week, randomized, double-blind clinical trials received at least 1 dose of umeclidinium 62.5 mcg + fluticasone furoate/vilanterol 100 mcg/25 mcg or placebo + fluticasone furoate/vilanterol 100 mcg/25 mcg administered once daily (mean age: 64 years, 92% white, 66% male across all treatments) [see Clinical Studies (14)]. The incidence of adverse reactions associated with the use of umeclidinium 62.5 mcg + fluticasone furoate/vilanterol 100 mcg/25 mcg presented in Table 1 is based on the two 12-week trials. Table 1. Adverse Reactions with Umeclidinium + Fluticasone Furoate/Vilanterol with ≥1% Incidence and More Common than Placebo + Fluticasone Furoate/Vilanterol (Trials 1 and 2) Adverse Reaction Umeclidinium + Fluticasone Furoate/ Vilanterol (n = 412) % Placebo + Fluticasone Furoate/ Vilanterol (n = 412) % Nervous system disorders Headache 4 3 Dysgeusia 2 <1 Musculoskeletal and connective tissue disorders Back pain 4 2 Respiratory, thoracic, and mediastinal disorders Cough 1 <1 Oropharyngeal pain 1 0 Gastrointestinal disorders Diarrhea 2 <1 Infections and infestations Gastroenteritis 1 0 Trial 3 - Long-term Safety Data A 52-week trial (Trial 3) evaluated the long-term safety of TRELEGY ELLIPTA compared with the fixed-dose combinations of fluticasone furoate/vilanterol 100 mcg/25 mcg and umeclidinium/vilanterol 62.5 mcg/25 mcg. A total of 10,355 subjects with COPD with a history of moderate or severe exacerbations within the prior 12 months were randomized (2:2:1) to receive TRELEGY ELLIPTA, fluticasone furoate/vilanterol, or umeclidinium/vilanterol administered once daily in a double-blind clinical trial (mean age: 65 years, 77% white, 66% male across all treatments) [see Clinical Studies (14)]. The incidence of adverse reactions in the long-term trial were consistent with those in Trials 1 and 2. However, in addition to the adverse reactions shown in Table 1, adverse reactions occurring in ≥1% of the subjects treated with TRELEGY ELLIPTA (n = 4,151) for up to 52 weeks also included upper respiratory tract infection, pneumonia [see Warnings and Precautions (5.5)], bronchitis, oral candidiasis [see Warnings and Precautions (5.4)], arthralgia, influenza, sinusitis, pharyngitis, rhinitis, constipation, urinary tract infection, and dysphonia.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION TRELEGY ELLIPTA should be administered as 1 inhalation once daily by the orally inhaled route only. After inhalation, the patient should rinse his/her mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis. TRELEGY ELLIPTA should be used at the same time every day. Do not use TRELEGY ELLIPTA more than 1 time every 24 hours. No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment [see Clinical Pharmacology (12.3)]. •For oral inhalation only. (2) •Maintenance treatment of COPD: 1 inhalation of TRELEGY ELLIPTA once daily. (2)
Use in special populations
8 USE IN SPECIFIC POPULATIONS Hepatic impairment: Fluticasone furoate systemic exposure may increase in patients with moderate or severe impairment. Monitor for systemic corticosteroid effects. (8.6, 12.3) 8.1 Pregnancy 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 9 and 40 times the maximum recommended human daily inhalation doses (MRHDID) of 100 and 25 mcg in adults, respectively. (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 50 and 200 times, respectively, the human exposure at the MRHDID. 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 and 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 9 and 40 times the MRHDID, 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 9 and 2 times the MRHDID, respectively (on a mcg/m2 basis at maternal inhalation doses up to 91 and 8 mcg/kg/day). 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 3 times the MRHDID (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 via inhalation 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 at doses up to approximately 26 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 1,000 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 160 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 1,000 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. 8.2 Lactation 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 is present in rat 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 Animal Data: Subcutaneous administration of umeclidinium to lactating rats at approximately 25 times the MRHDID resulted in a quantifiable level of umeclidinium in 2 of 54 pups, which may indicate transfer of umeclidinium in rat milk. 8.4 Pediatric Use TRELEGY ELLIPTA is not indicated for use in children. The safety and efficacy in pediatric patients have not been established. 8.5 Geriatric Use 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 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 mcg/25 mcg. In Trial 3, 2,265 subjects aged 65 years and older, of which 565 subjects were aged 75 years and older, were administered TRELEGY ELLIPTA. 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. 8.6 Hepatic Impairment 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. 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)]. 8.7 Renal Impairment 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)].

Interactions

7 DRUG INTERACTIONS •Strong cytochrome P450 3A4 inhibitors (e.g., ketoconazole): Use with caution. May cause systemic corticosteroid and cardiovascular effects. (7.1) •Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of vilanterol on vascular system. (7.2) •Beta-blockers: Use with caution. May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. (7.3) •Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists. (7.4) •Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of TRELEGY ELLIPTA with other anticholinergic-containing drugs. (7.5) 7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone furoate and vilanterol are substrates of CYP3A4. Concomitant administration of the strong CYP3A4 inhibitor ketoconazole increases the systemic exposure to fluticasone furoate and vilanterol. Caution should be exercised when considering the coadministration of TRELEGY ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) [see Warnings and Precautions (5.9), Clinical Pharmacology (12.3)]. 7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Vilanterol, like other beta2-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias. 7.3 Beta-adrenergic Receptor Blocking Agents Beta-blockers not only block the pulmonary effect of beta-agonists, such as vilanterol, but may also produce severe bronchospasm in patients with COPD. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents for these patients; cardioselective beta-blockers could be considered, although they should be administered with caution. 7.4 Non–Potassium-Sparing Diuretics The electrocardiographic changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with non–potassium-sparing diuretics. 7.5 Anticholinergics There is potential for an additive interaction with concomitantly used anticholinergic medicines. Therefore, avoid coadministration of TRELEGY ELLIPTA with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects [see Warnings and Precautions (5.14, 5.15)].

More information

Category Value
Authorisation number NDA209482
Agency product number 40AHO2C6DG
Orphan designation No
Product NDC 0173-0887
Date Last Revised 24-04-2018
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder GlaxoSmithKline LLC