Trelegy Ellipta

Generic name: fluticasone, umeclidinium, and vilanterol
Drug class: Bronchodilator combinations

Medically reviewed by  A Ras MD.

What is Trelegy Ellipta?

Trelegy Ellipta combines 3 medicines in one inhaler, an inhaled corticosteroid (ICS) medicine (fluticasone furoate), an anticholinergic medicine (umeclidinium), and a long-acting beta2-adrenergic agonist (LABA) medicine (vilanterol).

• ICS medicines such as fluticasone furoate help to decrease inflammation in the lungs. Inflammation in the lungs can lead to breathing problems.
• Anticholinergic medicines such as umeclidinium and LABA medicines such as vilanterol help the muscles around the airways in your lungs stay relaxed to prevent symptoms such as wheezing, cough, chest tightness, and shortness of breath. These symptoms can happen when the muscles around the airways tighten. This makes it hard to breathe.
• Trelegy Ellipta is a prescription medicine used long term (chronic) to treat people with chronic obstructive pulmonary disease (COPD). COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both.
• Trelegy Ellipta is used as 1 inhalation 1 time each day to improve symptoms of COPD for better breathing and to reduce the number of flare-ups (the worsening of your COPD symptoms for several days).
• Trelegy Ellipta is not approved for the treatment of asthma. Trelegy Ellipta contains vilanterol. LABA medicines such as vilanterol when used alone increase the risk of hospitalizations and death from asthma problems. Trelegy Ellipta contains an ICS, an anticholinergic, and a LABA. When an ICS and LABA are used together, there is not a significant increased risk in hospitalizations and death from asthma problems.
• Trelegy Ellipta is not used to relieve sudden breathing problems and will not replace a rescue inhaler. Always have a rescue inhaler (an inhaled, short-acting bronchodilator) with you to treat sudden breathing problems. If you do not have a rescue inhaler, contact your healthcare provider to have one prescribed for you.
• Trelegy Ellipta should not be used in children. It is not known if Trelegy Ellipta is safe and effective in children.

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 C27H29F3O6S. 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 C29H34NO2•Br (as a quaternary ammonium bromide compound). It is slightly soluble in water.

Vilanterol trifenatate has the chemical name triphenylacetic acid-4-{(1R)-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 C24H33Cl2NO5•C20H16O2. 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 inhaler is activated, the powder within both blisters is exposed and ready for dispersion into the airstream created by the patient inhaling through the mouthpiece.

Under standardized in vitro test conditions, TRELEGY ELLIPTA delivers 92 or 184 mcg of fluticasone furoate, 55 mcg of umeclidinium, and 22 mcg of vilanterol per dose when tested at a flow rate of 60 L/min for 4 seconds. At flow rates of 30, 60, and 90 L/min for 4 seconds under in vitro test conditions, TRELEGY ELLIPTA delivers ≥90% of the target dose for each component.

In adult subjects with very severe COPD (FEV1/FVC [forced vital capacity] <70% and FEV1 <30% predicted), mean peak inspiratory flow through the ELLIPTA inhaler was 65.8 L/min (range: 43.5 to 94.1 L/min).

In adult subjects with severe asthma, mean peak inspiratory flow through the ELLIPTA inhaler was 96.6 L/min (range: 72.4 to 124.6 L/min).

The actual amount of drug delivered to the lung will depend on patient factors, such as inspiratory flow profile.

Mechanism of Action

TRELEGY ELLIPTA

TRELEGY ELLIPTA contains fluticasone furoate, umeclidinium, and vilanterol. The mechanisms of action described below for the individual components apply to TRELEGY ELLIPTA. These drugs represent 3 different classes of medications (an ICS, an anticholinergic, and a LABA), each having different effects on clinical and physiological indices.

Fluticasone Furoate

Fluticasone furoate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate. The clinical relevance of these findings is unknown.

The precise mechanism through which fluticasone furoate affects COPD and asthma symptoms is not known. Inflammation is an important component in the pathogenesis of COPD and asthma. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. Specific effects of fluticasone furoate demonstrated in in vitro and in vivo models included activation of the glucocorticoid response element, inhibition of pro-inflammatory transcription factors such as NFkB, and inhibition of antigen-induced lung eosinophilia in sensitized rats. These anti-inflammatory actions of corticosteroids may contribute to their efficacy.

Umeclidinium

Umeclidinium is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of umeclidinium is predominantly a site-specific effect.

Vilanterol

Vilanterol is a LABA. In vitro tests have shown the functional selectivity of vilanterol was similar to salmeterol. The clinical relevance of this in vitro finding is unknown.

Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects.

The pharmacologic effects of beta2-adrenergic agonist drugs, including vilanterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3ʹ,5ʹ-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Who should not use Trelegy Ellipta?

Do not use Trelegy Ellipta if you:

• have a severe allergy to milk proteins. Ask your healthcare provider if you are not sure.
• are allergic to fluticasone furoate, umeclidinium, vilanterol, or any of the ingredients in Trelegy Ellipta. See the end of this Patient Information for a complete list of ingredients in Trelegy Ellipta.

What should I tell my healthcare provider before using Trelegy Ellipta?

Before using Trelegy Ellipta, tell your healthcare provider about all of your medical conditions, including if you:

• have heart problems.
• have high blood pressure.
• have seizures.
• have thyroid problems.
• have diabetes.
• have liver problems.
• have weak bones (osteoporosis).
• have an immune system problem.
• have eye problems such as glaucoma, increased pressure in your eye, cataracts, blurred vision, or other changes in vision. Trelegy Ellipta may make your glaucoma worse.
• are allergic to milk proteins.
• have prostate or bladder problems, or problems passing urine. Trelegy Ellipta may make these problems worse.
• have any type of viral, bacterial, parasitic, or fungal infection.
• are exposed to chickenpox or measles.
• are pregnant or plan to become pregnant. It is not known if Trelegy Ellipta may harm your unborn baby.
• are breastfeeding. It is not known if the medicines in Trelegy Ellipta pass into your milk and if they can harm your baby.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Trelegy Ellipta and certain other medicines may interact with each other. This may cause serious side effects.

Especially tell your healthcare provider if you take:

• anticholinergics (including tiotropium, ipratropium, aclidinium)
• atropine
• other LABA (including salmeterol, formoterol, arformoterol, olodaterol, and indacaterol)
• antifungal or anti-HIV medicines.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I use Trelegy Ellipta?

Read the step-by-step instructions for use that come with Trelegy Ellipta.

• Do not use Trelegy Ellipta unless your healthcare provider has taught you how to use the inhaler and you understand how to use it correctly.
• Use Trelegy Ellipta exactly as your healthcare provider tells you to use it. Do not use Trelegy Ellipta more often than prescribed.
• Use 1 inhalation of Trelegy Ellipta 1 time each day. Use Trelegy Ellipta at the same time each day.
• If you miss a dose of Trelegy Ellipta, take it as soon as you remember. Do not take more than 1 inhalation per day. Take your next dose at your usual time. Do not take 2 doses at 1 time.
• If you take too much Trelegy Ellipta, call your healthcare provider or go to the nearest hospital emergency room right away if you have any unusual symptoms, such as worsening shortness of breath, chest pain, increased heart rate, or shakiness.
• Do not use other medicines that contain a LABA or an anticholinergic for any reason. Ask your healthcare provider or pharmacist if any of your other medicines are LABA or anticholinergic medicines.
• Do not stop using Trelegy Ellipta unless told to do so by your healthcare provider because your symptoms might get worse. Your healthcare provider will change your medicines as needed.
• Trelegy Ellipta does not relieve sudden symptoms of COPD and you should not take extra doses of Trelegy Ellipta to relieve these sudden symptoms. Always have a rescue inhaler with you to treat sudden symptoms. If you do not have a rescue inhaler, call your healthcare provider to have one prescribed for you.
• Call your healthcare provider or get medical care right away if:
  • your breathing problems get worse.
  • you need to use your rescue inhaler more often than usual.
  • your rescue inhaler does not work as well to relieve your symptoms.

What are the possible side effects of Trelegy Ellipta?

Trelegy Ellipta can cause serious side effects, including:

• fungal infection in your mouth or throat (thrush). Rinse your mouth with water without swallowing after using Trelegy Ellipta to help reduce your chance of getting thrush.
• pneumonia. People with COPD have a higher chance of getting pneumonia. Trelegy Ellipta may increase the chance of getting pneumonia. Call your healthcare provider if you notice any of the following symptoms:
  • increase in mucus (sputum) production
  • change in mucus color
  • fever
  • chills
  • increased cough
  • increased breathing problems
• weakened immune system and increased chance of getting infections (immunosuppression).
• reduced adrenal function (adrenal insufficiency). Adrenal insufficiency is a condition where the adrenal glands do not make enough steroid hormones. This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and start taking a medicine containing an ICS (such as Trelegy Ellipta). During this transition period, when your body is under stress from fever, trauma (such as a car accident), infection, surgery, or worse COPD symptoms, adrenal insufficiency can get worse and may cause death.
• Symptoms of adrenal insufficiency include:
  • feeling tired
  • lack of energy
  • weakness
  • nausea and vomiting
  • low blood pressure (hypotension)
• sudden breathing problems immediately after inhaling your medicine. If you have sudden breathing problems immediately after inhaling your medicine, stop taking Trelegy Ellipta and call your healthcare provider right away.
• serious allergic reactions. Call your healthcare provider or get emergency medical care if you get any of the following symptoms of a serious allergic reaction:
  • rash
  • hives
  • swelling of your face, mouth, and tongue
  • breathing problems
• effects on heart.
  • increased blood pressure
  • a fast or irregular heartbeat, awareness of heartbeat
  • chest pain
• effects on nervous system.
  • tremor
  • nervousness
• bone thinning or weakness (osteoporosis).
• eye problems including glaucoma, increased pressure in your eye, cataracts, blurred vision, worsening of narrow-angle glaucoma, or other changes in vision. You should have regular eye exams while using Trelegy Ellipta.
  Acute narrow-angle glaucoma can cause permanent loss of vision if not treated. Symptoms of acute narrow-angle glaucoma may include:
  • eye pain or discomfort
  • nausea or vomiting
  • blurred vision
  • seeing halos or bright colors around lights
  • red eyes
    If you have these symptoms, call your healthcare provider right away before taking another dose.
• urinary retention. People who take Trelegy Ellipta may develop new or worse urinary retention. Symptoms of urinary retention may include:
  • difficulty urinating
  • painful urination
  • urinating frequently
  • urination in a weak stream or drips
    If you have these symptoms of urinary retention, stop taking Trelegy Ellipta, and call your healthcare provider right away before taking another dose.
• changes in laboratory blood values, including high levels of blood sugar (hyperglycemia) and low levels of potassium (hypokalemia).

Common side effects of Trelegy Ellipta include:

• upper respiratory tract infection
• pneumonia
• bronchitis
• thrush in your mouth and throat. Rinse your mouth with water without swallowing after use to help prevent this.
• headache
• back pain
• joint pain
• flu
• inflammation of the sinuses
• runny nose and sore throat
• taste disturbance
• constipation
• painful and frequent urination
• (signs of a urinary tract infection)
• nausea, vomiting, and diarrhea
• mouth and throat pain
• cough
• hoarseness

These are not all the possible side effects of Trelegy Ellipta.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Trelegy Ellipta

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Trelegy Ellipta for a condition for which it was not prescribed. Do not give Trelegy Ellipta to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about Trelegy Ellipta that is written for health professionals.

How should I store Trelegy Ellipta?

• Store Trelegy Ellipta at room temperature between 68°F and 77°F (20°C and 25°C). Keep in a dry place away from heat and sunlight.
• Store Trelegy Ellipta in the unopened tray and only open when ready for use.
• Safely throw away Trelegy Ellipta in the trash 6 weeks after you open the tray or when the counter reads “0”, whichever comes first. Write the date you open the tray on the label on the inhaler.

Keep Trelegy Ellipta and all medicines out of the reach of children.

What are the ingredients in Trelegy Ellipta?

Active ingredients: fluticasone furoate, umeclidinium, vilanterol

Inactive ingredients: lactose monohydrate (contains milk proteins), magnesium stearate

Label

PRINCIPAL DISPLAY PANEL