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Fluticasone Furoate, Umeclidinium Bromide And Vilanterol Trifenatate
FDA Drug Information • Also known as: Trelegy Ellipta
- Brand Names
- Trelegy Ellipta
- Route
- RESPIRATORY (INHALATION)
- Dosage Form
- POWDER
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION TRELEGY ELLIPTA is an inhalation powder drug product for delivery of a combination of fluticasone furoate (an ICS), umeclidinium (an anticholinergic), and vilanterol (a LABA) to patients by oral inhalation. Fluticasone furoate, a synthetic trifluorinated corticosteroid, has the chemical name (6α,11β,16α,17α)-6,9-difluoro-17-{[(fluoro-methyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl 2-furancarboxylate and the following chemical structure: Fluticasone furoate is a white powder with a molecular weight of 538.6, and the empirical formula is C 27 H 29 F 3 O 6 S. It is practically insoluble in water. Umeclidinium bromide has the chemical name 1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-azoniabicyclo[2.2.2]octane bromide and the following chemical structure: Umeclidinium bromide is a white powder with a molecular weight of 508.5, and the empirical formula is C 29 H 34 NO 2
Br (as a quaternary ammonium bromide compound). It is slightly soluble in water. Vilanterol trifenatate has the chemical name triphenylacetic acid-4-{(1 R )-2-[(6-{2-[2,6-dicholorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol (1:1) and the following chemical structure: Vilanterol trifenatate is a white powder with a molecular weight of 774.8, and the empirical formula is C 24 H 33 Cl 2 NO 5 C 20 H 16 O 2 . It is practically insoluble in water. TRELEGY ELLIPTA is a light grey and beige plastic inhaler containing 2 foil blister strips. Each blister on one strip contains a white powder blend of micronized fluticasone furoate (100 or 200 mcg) and lactose monohydrate (12.4 or 12.3 mg) and each blister on the other strip contains a white powder blend of micronized umeclidinium bromide (74.2 mcg equivalent to 62.5 mcg of umeclidinium), micronized vilanterol trifenatate (40 mcg equivalent to 25 mcg of vilanterol), magnesium stearate (75 mcg), and lactose monohydrate (12.3 mg). The lactose monohydrate contains milk proteins. After the...What Is Fluticasone Furoate, Umeclidinium Bromide And Vilanterol Trifenatate Used For?
1 INDICATIONS AND USAGE TRELEGY ELLIPTA is a combination of fluticasone furoate, an inhaled corticosteroid (ICS); umeclidinium, an anticholinergic; and vilanterol, a long-acting beta 2 -adrenergic agonist (LABA), indicated for:
the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). ( 1.1 ) the maintenance treatment of asthma in patients aged 18 years and older. ( 1.2 ) Limitations of Use: Not indicated for relief of acute bronchospasm. ( 1.3 , 5.2 ) 1.1 Maintenance Treatment of Chronic Obstructive Pulmonary Disease TRELEGY ELLIPTA is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). 1.2 Maintenance Treatment of Asthma TRELEGY ELLIPTA is indicated for the maintenance treatment of asthma in patients aged 18 years and older. 1.3 Limitations of Use TRELEGY ELLIPTA is NOT indicated for the relief of acute bronchospasm.Dosage and Administration
2 DOSAGE AND ADMINISTRATION
For oral inhalation only. ( 2.1 ) Maintenance treatment of COPD: 1 actuation of TRELEGY ELLIPTA 100/62.5/25 mcg once daily administered by oral inhalation. ( 2.2 ) Maintenance treatment of asthma: 1 actuation of TRELEGY ELLIPTA 100/62.5/25 mcg or TRELEGY ELLIPTA 200/62.5/25 mcg once daily administered by oral inhalation. ( 2.3 ) 2.1 Dosage and Administration Overview Administer 1 actuation of TRELEGY ELLIPTA once daily by oral inhalation. After inhalation, rinse the 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 )] . 2.2 Recommended Dosage for Maintenance Treatment of Chronic Obstructive Pulmonary Disease The recommended dosage of TRELEGY ELLIPTA for maintenance treatment of COPD is fluticasone furoate 100 mcg, umeclidinium 62.5 mcg, and vilanterol 25 mcg (1 actuation of TRELEGY ELLIPTA 100/62.5/25 mcg) once daily by oral inhalation. TRELEGY ELLIPTA 100/62.5/25 mcg is the only strength indicated for the treatment of COPD. If shortness of breath occurs in the period between doses, an inhaled, short-acting beta 2 -agonist (rescue medicine, e.g., albuterol) should be used for immediate relief. 2.3 Recommended Dosage for Maintenance Treatment of Asthma The recommended starting dosage of TRELEGY ELLIPTA for maintenance treatment of asthma is fluticasone furoate 100 mcg, umeclidinium 62.5 mcg, and vilanterol 25 mcg (1 actuation of TRELEGY ELLIPTA 100/62.5/25 mcg) or fluticasone furoate 200 mcg, umeclidinium 62.5 mcg, and vilanterol 25 mcg (1 actuation of TRELEGY ELLIPTA 200/62.5/25 mcg) once daily, by oral inhalation. When choosing the starting dosage strength of TRELEGY ELLIPTA, consider the patients’ disease severity; their previous asthma therapy, including the inhaled corticosteroid (ICS) dosage; as well as the patients’ current control of asthma symptoms and risk of future exacerbation. The maximum recommended dosage is 1 inhalation of TRELEGY ELLIPTA 200/62.5/25 mcg once daily. For patients who do not respond adequately to TRELEGY ELLIPTA 100/62.5/25 mcg once daily, increasing the dose to TRELEGY ELLIPTA 200/62.5/25 mcg once daily may provide additional improvement in asthma control. For patients who do not respond adequately to TRELEGY ELLIPTA 200/62.5/25 mcg once daily, re-evaluate and consider other therapeutic regimens and additional therapeutic options. If asthma symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist (rescue medicine, e.g., albuterol) should be used for immediate relief.Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling:
Serious Asthma-Related Events – Hospitalizations, Intubations, Death [see Warnings and Precautions ( 5.1 )] Oropharyngeal Candidiasis [see Warnings and Precautions ( 5.4 )] Increased Risk of Pneumonia in COPD [see Warnings and Precautions ( 5.5 )] Immunosuppression and Risk of Infections [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 )] 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. COPD: 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 ) Asthma: Most common adverse reactions (incidence ≥2%) are pharyngitis/nasopharyngitis, upper respiratory tract infection/viral upper respiratory tract infection, bronchitis, respiratory tract infection/viral respiratory tract infection, sinusitis/acute sinusitis, urinary tract infection, rhinitis, influenza, headache, and back pain. ( 6.2 ) 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 in Chronic Obstructive Pulmonary Disease The safety of TRELEGY ELLIPTA in COPD 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 100/62.5/25 mcg compared with the fixed-dose combinations of fluticasone furoate/vilanterol and umeclidinium/vilanterol [see Clinical Studies ( 14.1 )] . 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 100/25 mcg or placebo + fluticasone furoate/vilanterol 100/25 mcg administered once daily (mean age: 64 years, 92% White, 66% male across all treatments) [see Clinical Studies ( 14.1 )] . The incidence of adverse reactions associated with the use of umeclidinium 62.5 mcg + fluticasone furoate/vilanterol 100/25 mcg presented in Table 2 is based on the two 12-week trials. Table 2. Adverse Reactions with Umeclidinium + Fluticasone Furoate/Vilanterol with ≥1% Incidence and More Common than Placebo + Fluticasone Furoate/Vilanterol in Subjects with COPD (Trials 1 and 2) Umec = Umeclidinium, FF/VI = Fluticasone Furoate/Vilanterol. Adverse Reaction Umec + FF/VI (n = 412) % Placebo + FF/VI (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 100/62.5/25 mcg compared with the...Drug 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 cardiovascular 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 ketoconazole and other known strong CYP3A4 inhibitors [see Warnings and Precautions ( 5.9 ), Clinical Pharmacology ( 12.3 )] . 7.2 Monoamine Oxidase Inhibitors, Tricyclic Antidepressants, and QTc Prolonging Drugs Vilanterol, like other beta 2 -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 or asthma. Therefore, patients with COPD or asthma 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...Contraindications
4 CONTRAINDICATIONS TRELEGY ELLIPTA is contraindicated in the following conditions:
Primary treatment of status asthmaticus or other acute episodes of COPD or asthma where intensive measures are required [see Warnings and Precautions ( 5.2 )] . Severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone furoate, umeclidinium, vilanterol, or any of the excipients [see Warnings and Precautions ( 5.11 ), Description ( 11 )] . Primary treatment of status asthmaticus or acute episodes of COPD or asthma requiring intensive measures. ( 4 ) Severe hypersensitivity to milk proteins or any ingredients. ( 4 )Pregnancy and Breastfeeding
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 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...
Overdosage
10 OVERDOSAGE TRELEGY ELLIPTA contains fluticasone furoate, umeclidinium, and vilanterol; therefore, the risks associated with overdosage for the individual components described below apply to TRELEGY ELLIPTA. Treatment of overdosage consists of discontinuation of TRELEGY ELLIPTA together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medicine can produce bronchospasm. Cardiac monitoring is recommended in cases of overdosage. Fluticasone Furoate Because of low systemic bioavailability (15.2%) and an absence of acute drug-related systemic findings in clinical trials, overdosage of fluticasone furoate is unlikely to require any treatment other than observation. If used at excessive doses for prolonged periods, systemic effects such as hypercorticism may occur [see Warnings and Precautions (5.8)] . Umeclidinium High doses of umeclidinium may lead to anticholinergic signs and symptoms. Vilanterol The expected signs and symptoms with overdosage of vilanterol are those of excessive beta‑adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms of beta-adrenergic stimulation (e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, metabolic acidosis). As with all inhaled sympathomimetic medicines, cardiac arrest and even death may be associated with an overdose of vilanterol.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING TRELEGY ELLIPTA is supplied as a disposable light grey and beige plastic inhaler containing 2 foil strips, each with 30 blisters (or 14 blisters for the institutional pack). One strip contains fluticasone furoate (100 or 200 mcg per blister), and the other strip contains a blend of umeclidinium and vilanterol (62.5 and 25 mcg per blister, respectively). A blister from each strip is used to create 1 dose. The inhaler is packaged within a moisture-protective foil tray with a desiccant and a peelable lid in the following packs: NDC 0173-0887-10 TRELEGY ELLIPTA 100/62.5/25 mcg 30 inhalations (60 blisters) NDC 0173-0887-14 TRELEGY ELLIPTA 100/62.5/25 mcg 14 inhalations (28 blisters), institutional pack NDC 0173-0893-10 TRELEGY ELLIPTA 200/62.5/25 mcg 30 inhalations (60 blisters) NDC 0173-0893-14 TRELEGY ELLIPTA 200/62.5/25 mcg 14 inhalations (28 blisters), institutional pack Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) [See USP Controlled Room Temperature]. Store in a dry place away from direct heat or sunlight. Keep out of reach of children. TRELEGY ELLIPTA should be stored inside the unopened moisture-protective foil tray and only removed from the tray immediately before initial use. Discard TRELEGY ELLIPTA 6 weeks after opening the foil tray or when the counter reads “0” (after all blisters have been used), whichever comes first. The inhaler is not reusable. Do not attempt to take the inhaler apart.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.