Trelegy Ellipta for COPD: What Pharmacists Should Know

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease, affecting more than 30 million Americans.¹ It is the third leading cause of death in the United States and presents a significant burden on the health care system through direct medical costs and reduced productivity.

In September 2017, the FDA approved GSK’s Trelegy Ellipta, a combination of fluticasone furoate (an inhaled corticosteroid), umeclidinium (an anticholinergic), and vilanterol (a long-acting beta-2-adrenergic agonist) indicated for the long-term maintenance treatment of patients with COPD. With its approval, Trelegy Ellita became the first once-daily product that combines 3 active ingredients in a single inhaler for maintenance treatment of COPD.

Here are key therapeutics areas with Trelegy Ellipta that every pharmacist should know.

Indication2

Trelegy Ellipta is indicated for the long-term, once-daily, maintenance treatment of patients with COPD, including chronic bronchitis and/or emphysema, who (1) are on a fixed-dose combination of fluticasone furoate and vilanterol for airflow obstruction and reducing exacerbations in whom additional treatment of airflow obstruction is desired or (2) for patients who are already receiving umeclidinium and a fixed-dose combination of fluticasone furoate and vilanterol.

Limitation of Use

Trelegy Ellipta is not indicated for the relief of acute bronchospasm or for the treatment of asthma. Additionally, the medication is not indicated for use in children, as its safety and efficacy in this population has not been established.

Mechanism of Action

Trelegy Ellipta is a combination of 3 different classes of medication. Fluticasone furoate is an inhaled corticosteroid that has been shown to have a wide range of actions on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (eg, histamine, eicosanoids, cytokines) involved in reducing inflammation.

Umeclidinium is a long-acting muscarinic antagonist, which exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. Vilanterol is a long-acting beta-2-adrenergic agonist (LABA), which is thought to exert its effect through increasing cyclic AMP levels, causing the relaxation of the bronchial smooth muscle and the inhibition of the release of mediators of immediate hypersensitivity from cells.

Formulation and Storage

Trelegy Ellipta is supplied as a disposable plastic inhaler containing 2 foil strips, each with 30 blisters or 14 blisters for the institutional pack. One strip contains fluticasone furoate (100 mcg per blister), and the other strip contains a blend of umeclidinium and vilanterol (62.5 mcg and 25 mcg per blister). A blister from each strip is used to create 1 dose.

Trellegy Ellipta should be stored at room temperature in a dry place away from direct hear or sunlight.

Dosing

The recommended dose is 1 inhalation once daily. Trelegy Ellipta should be used at the same time every day.

No dosage adjustment is required for geriatric patients, individuals with renal impairment, or those with moderate hepatic function.

Efficacy

The efficacy of Trelegy Ellipta to treat COPD was established in 2 multicenter, randomized, double-blind, parallel-group, 12-week treatment trials. At screening, the mean post-bronchodilator percent predicted FEV1 was 46% and the mean percent reversibility was 13% in both studies. The primary endpoint was change from baseline in pre-dose FEV1 at Day 85, defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous dose on Day 84.

For both trials 1 and 2, Trelegy Ellipta demonstrated a statistically significant increase in the primary endpoint relative to placebo + fluticasone furoate/vilanterol. Similar results were demonstrated for the secondary endpoint of the weighted mean FEV1 (0 to 6 hours post-dose) on Day 84. Additionally, across both trials over 12 weeks, patients treated with Trelegy Ellipta used less recue medication on average, compared with subjects treated with placebo + fluticasone furoate/vilanterol. Neither trial evaluated the effect of Trelegy Ellipta vilanterol on the rate of COPD exacerbations.

Safety

The most common adverse reactions of Trelegy Ellipta reported in clinical trials include headache, back pain, distorted taste, diarrhea, and cough.

Trelegy Ellipta is contraindicated in patients with a severe hypersensitivity to milk proteins. The safety and effectiveness of the medication have not been established in pediatric patients. Additionally, like all LABAs, the medication has a black box warning for an increased risk of asthma-related deaths.

Product Comparison³

Manufacturer

FDA Indication

Dosing

Trelegy Ellipta (fluticasone/ vilanterol/umeclidinium)

GSK

COPD

1 inhalation QD

Breo Ellipta (fluticasone/ vilanterol)

GSK

COPD, asthma

1 inhalation QD

Anoro Ellipta

(vilanterol/ umeclidinium)

GSK

COPD

1 inhalation QD

Advair Diskus

(fluticasone/salmeterol)

GSK

COPD, asthma

1 inhalation BID

AirDuo Respiclick (fluticasone/salmeterol)

Teva

Asthma

1 inhalation BID

Symbicort

(budesonide/formoterol)

AstraZeneca

COPD, asthma

2 inhalations BID

Dulera (mometasone/formoterol)

Merck

Asthma

2 inhalations BID

Stiolto Respimat (tiotropium/olodaterol)

Boehringer Ingelheim

COPD

2 inhalations QD

Counseling Points²

Patients should be instructed to throw Trelegy Ellipta away 6 weeks after opening the tray or when the counter reads “0," whichever comes first. It may be helpful to write the date of opening on the tray on the label of the inhaler.

After inhalation, patients should be instructed to rinse their mouths with water without swallowing. Trelegy Ellipta should not be used more than 1 time every 24 hours.

If you open and close the cover without inhaling the medicine, you will lose the dose. The lost dose will be securely held inside the inhaler, but it will no longer be available to be inhaled. Therefore, patients should be counseled that it is not possible to accidentally take a double dose or an extra dose in 1 inhalation.

Patients should be informed that Trelegy Ellipta is not meant to relieve acute symptoms of COPD and extra doses should not be used for that purpose.

Conclusion

Trelegy Ellipta is the first once-daily single inhaler combining 3 ingredients for the treatment of COPD. In clinical studies, Trelegy Ellipta was shown to be highly effective in improving respiratory laboratory endpoints compared to placebo + fluticasone furoate/vilanterol. In safety analyses, no major safety concerns were found unique to this specific product. The exact place in therapy for Trelegy Ellipta has not been established. However, the medication may be particular advantageous in improving adherence and reducing out-of-pocket costs, as patients will only have to pay a single copay for 3 distinct ingredients.

References

1. COPD Foundation. COPD statistics across America. copdfoundation.org/What-is-COPD/COPD-Facts/Statistics.aspx. Accessed November 25, 2017.

2. Trelegy Ellipta [Prescribing Information]. Research Triangle Park, NC: GlaxoSmithKline; 2017. gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Trelegy/pdf/TRELEGY-PI-MG-IFU.PDF. Accessed December 4, 2017.

3. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc; November 25, 2017.