Anoro Ellipta
umeclidinium / vilanterol
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| COPD — maintenance treatment | Adults | Dual bronchodilator (LAMA + LABA) | FDA Approved |
Umeclidinium-vilanterol is indicated for the long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and emphysema. It improves symptoms and reduces the frequency of exacerbations through the additive bronchodilation provided by combining muscarinic blockade with beta-2 agonism. It does not contain an inhaled corticosteroid and is therefore not suitable for patients requiring anti-inflammatory airway therapy.
Anoro Ellipta is NOT indicated for the treatment of asthma. The safety and efficacy in asthma have not been established. Use of a LABA (vilanterol) without an inhaled corticosteroid in patients with asthma is associated with an increased risk of asthma-related death (LABA class effect). This contraindication is explicitly stated in the FDA-approved labelling.
Asthma-COPD overlap (ACO) — as add-on to ICS: In practice, some clinicians prescribe Anoro Ellipta alongside a separate ICS inhaler for patients with features of both COPD and asthma. Evidence quality: Low. This use is not FDA-approved; dedicated ACO trials with this combination have not been conducted. Trelegy Ellipta (which adds fluticasone furoate) is a more appropriate single-inhaler option when ICS is also needed.
Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| COPD maintenance — initial dual bronchodilator therapy | 62.5/25 mcg, 1 inhalation once daily | 62.5/25 mcg, 1 inhalation once daily | 62.5/25 mcg once daily | Single strength only; do not exceed 1 inhalation/24 h Use at the same time each day |
| COPD — step-up from LAMA or LABA monotherapy | 62.5/25 mcg, 1 inhalation once daily | 62.5/25 mcg, 1 inhalation once daily | 62.5/25 mcg once daily | Discontinue separate LAMA and/or LABA inhalers when switching Appropriate for patients with persistent symptoms on monotherapy |
| COPD — exacerbation-prone patients without eosinophilic phenotype | 62.5/25 mcg, 1 inhalation once daily | 62.5/25 mcg, 1 inhalation once daily | 62.5/25 mcg once daily | GOLD recommends LAMA/LABA over ICS/LABA for exacerbation prevention when eosinophils are low If exacerbations persist or eosinophils ≥300 cells/µL, consider step-up to ICS/LAMA/LABA triple therapy |
Anoro Ellipta is available in a single strength only (62.5/25 mcg) with no dose titration required. The Ellipta dry powder inhaler needs no shaking, no priming, and no breath-actuation coordination. The patient opens the cover (loading the dose), breathes in steadily and deeply, then closes. The inhaler has a dose counter and should be discarded after 30 doses or 6 weeks from opening the foil tray, whichever comes first. No mouth rinsing is needed (no ICS component), but patients should have a separate rescue inhaler (e.g., albuterol) for acute symptoms.
Pharmacology
Mechanism of Action
Umeclidinium is a long-acting muscarinic antagonist (LAMA) with high affinity for the M1 through M5 receptor subtypes. Its therapeutic effect in COPD stems from competitive and reversible blockade of M3 muscarinic receptors on airway smooth muscle, preventing acetylcholine-mediated bronchoconstriction. The onset of bronchodilation begins within minutes of inhalation, and the duration extends beyond 24 hours, supporting once-daily dosing. The bronchodilation is predominantly a local site-specific effect in the airways.
Vilanterol is a selective, long-acting beta-2 adrenergic receptor agonist (LABA) that activates adenylyl cyclase in airway smooth muscle cells, increasing intracellular cyclic AMP and producing sustained relaxation of bronchial smooth muscle. Its duration of action exceeds 24 hours after a single inhaled dose. By combining muscarinic blockade (cholinergic pathway) with beta-2 stimulation (adrenergic pathway), Anoro Ellipta achieves additive bronchodilation greater than either agent alone, through two mechanistically distinct pathways.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | UMEC: Tmax 5–15 min; negligible oral bioavailability. VI: rapid pulmonary absorption; negligible contribution from swallowed portion | Bronchodilation onset within minutes; systemic exposure is primarily from the lung-absorbed fraction |
| Distribution | UMEC: Vd 86 L (IV), protein binding ~89%. VI: Vd 165 L (SS), protein binding ~94% | Both distribute beyond plasma volume; moderate-to-high protein binding limits free systemic drug |
| Metabolism | UMEC: primarily CYP2D6 (O-dealkylation, hydroxylation, conjugation); CYP2D6 poor metaboliser status does not clinically alter exposure. VI: CYP3A4 (O-dealkylation) to inactive metabolites | Strong CYP3A4 inhibitors increase vilanterol systemic exposure and cardiovascular effects; no dose adjustment needed for CYP2D6 polymorphisms |
| Elimination | UMEC: t½ ~11 h (effective); faecal 58%, urinary 22%. VI: t½ ~11 h (effective); urinary 70%, faecal 30% | Both support once-daily dosing; no dose adjustment needed for renal or moderate hepatic impairment |
Side Effects
| Adverse Effect | Incidence (Anoro / Placebo) | Clinical Note |
|---|---|---|
| Pharyngitis | 2% / <1% | Most commonly reported adverse event; generally mild sore throat |
| Diarrhoea | 2% / 1% | Usually mild and self-limiting; no dose adjustment needed |
| Pain in extremity | 2% / 1% | Musculoskeletal complaint; not clearly dose-related |
| Sinusitis | 1% / <1% | Comparable to rates seen with other inhaled bronchodilators |
| Lower respiratory tract infection | 1% / <1% | No ICS component means no additional pneumonia risk vs LAMA/LABA class |
| Constipation | 1% / <1% | Anticholinergic class effect from umeclidinium; advise adequate hydration and fibre intake |
| Muscle spasms | 1% / <1% | LABA class effect; usually transient tremor or cramping |
| Neck pain | 1% / <1% | Musculoskeletal; relationship to drug uncertain |
| Chest pain | 1% / <1% | Non-cardiac in most cases; evaluate cardiovascular causes if persistent or severe |
No adverse events reached the ≥10% (Very Common) threshold in clinical trials. Additional AEs from a 12-month safety trial (at the 125/25 mcg dose) included headache, back pain, cough, UTI, arthralgia, nausea, vertigo, abdominal pain, pleuritic pain, viral respiratory tract infection, toothache, and diabetes mellitus — all at ≥1% and more frequent than placebo.
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Paradoxical bronchospasm | Rare | Immediately after inhalation | Treat with rescue SABA; permanently discontinue Anoro; switch to alternative |
| Anaphylaxis / angioedema | Very rare (postmarketing) | Minutes to hours after dose | Emergency treatment; permanent discontinuation; do not rechallenge |
| Acute narrow-angle glaucoma | Rare; LAMA class effect | Hours to days | Emergency ophthalmology referral; discontinue if confirmed |
| Urinary retention | Uncommon; LAMA class effect | Days to weeks | Discontinue if significant; urology referral; higher risk with BPH |
| Cardiac arrhythmias (atrial fibrillation, ventricular/supraventricular extrasystoles) | Rare (postmarketing) | Variable | ECG monitoring; discontinue if clinically significant; cardiology referral |
| Myocardial infarction | Very rare (postmarketing) | Variable | Emergency cardiac care; discontinue; MACE rate in IMPACT trial was 2.2/100 pt-yr for UMEC/VI arm |
Unlike ICS-containing triple therapy combinations, Anoro Ellipta does not carry the increased pneumonia risk associated with inhaled corticosteroids. In the IMPACT trial, the pneumonia incidence was 5% with umeclidinium-vilanterol compared with 8% in the ICS-containing triple therapy arm (Trelegy). This makes Anoro Ellipta a favourable option for COPD patients who do not have an eosinophilic phenotype or frequent exacerbations warranting ICS.
Drug Interactions
Vilanterol is a CYP3A4 substrate, so strong CYP3A4 inhibitors are the most significant pharmacokinetic interaction. Umeclidinium interactions relate primarily to additive anticholinergic effects. Vilanterol also has pharmacodynamic interactions involving QTc prolongation, beta-blocker antagonism, and additive sympathomimetic effects.
Monitoring
- Lung Function (FEV1)Baseline, then every 3–6 months
RoutineAssess bronchodilator response. Improvement in trough FEV1 should be evident within 1–2 weeks. Declining values or increased rescue use may signal need for step-up to triple therapy. - COPD Exacerbation FrequencyEach visit
RoutineTrack exacerbation history. If exacerbations persist despite LAMA/LABA therapy, assess blood eosinophils and consider adding an ICS (stepping up to triple therapy). - Ophthalmological SymptomsEach visit in at-risk patients
Trigger-basedLAMA class risk for narrow-angle glaucoma. Ask about eye pain, blurred vision, visual halos. Urgent referral if acute symptoms develop. - Urinary SymptomsEach visit in at-risk patients
Trigger-basedLAMA class effect: monitor for urinary retention in patients with prostatic hyperplasia or bladder-neck obstruction. - Cardiovascular StatusBaseline and as indicated
Trigger-basedVilanterol can increase heart rate and blood pressure. Monitor patients with coronary insufficiency, arrhythmias, or hypertension. MACE rate was 2.2/100 patient-years in the IMPACT trial. - Serum PotassiumWhen concurrent diuretics or digoxin
Trigger-basedBeta-agonists can cause transient hypokalaemia via intracellular shift. In the 6-month COPD trials, no clinically significant treatment effect on potassium was observed at standard doses.
Contraindications & Cautions
Absolute Contraindications
- Asthma: Anoro Ellipta is NOT indicated for asthma. Use of LABA without ICS in asthma patients is associated with increased asthma-related death (LABA class effect). The PI explicitly contraindicates use of vilanterol without an ICS in patients with asthma.
- Severe hypersensitivity to milk proteins — the Ellipta inhaler contains lactose monohydrate with milk proteins.
- Known hypersensitivity to umeclidinium, vilanterol, or any excipient.
Relative Contraindications (Specialist Input Recommended)
- Narrow-angle glaucoma: Umeclidinium may precipitate or worsen acute angle-closure glaucoma.
- Prostatic hyperplasia or bladder-neck obstruction: Anticholinergic effects may worsen urinary retention.
- Severe cardiovascular disease: Coronary insufficiency, arrhythmias, or hypertension may be exacerbated by vilanterol’s beta-adrenergic effects.
Use with Caution
- Convulsive disorders: Beta-agonists can lower seizure threshold.
- Thyrotoxicosis: Vilanterol may exacerbate symptoms.
- Diabetes mellitus / ketoacidosis: Beta-agonists can cause transient hyperglycaemia.
- Severe hepatic impairment: Not studied; UMEC exposure may increase.
LABA monotherapy (without ICS) is associated with an increased risk of asthma-related death. The SMART trial showed a relative risk of 4.37 (95% CI: 1.25–15.34) for salmeterol monotherapy compared with placebo. This is a class effect of all LABAs, including vilanterol. Anoro Ellipta does not contain an ICS and is therefore explicitly contraindicated for asthma use. Available data do not suggest an increased risk of death with LABA use in COPD patients. For COPD patients who also have asthma features or require anti-inflammatory therapy, consider ICS-containing alternatives such as Trelegy Ellipta or Breo Ellipta.
Patient Counselling
Purpose of Therapy
Anoro Ellipta is a once-daily maintenance inhaler for COPD that combines two bronchodilators to keep airways open and reduce flare-ups. It is not a rescue inhaler and will not relieve sudden breathing difficulty. Patients must always carry a separate short-acting rescue inhaler. Anoro Ellipta is for COPD only and must never be used for asthma.
How to Take
Use Anoro once daily at the same time each day. Open the cover of the Ellipta inhaler fully until you hear a click (this loads the dose). Breathe out gently away from the inhaler, then place the mouthpiece in your mouth and breathe in steadily and deeply. Hold your breath for 3–4 seconds, then breathe out slowly. Close the cover. Unlike steroid-containing inhalers, mouth rinsing after each dose is not required. Discard the inhaler 6 weeks after opening the foil tray or when the dose counter reads 0, whichever comes first.
Sources
- Anoro Ellipta (umeclidinium and vilanterol) Prescribing Information. GlaxoSmithKline. Revised June 2025. DailyMedPrimary source for all dosing, contraindications, adverse reaction data, and pharmacokinetic parameters in this monograph.
- Anoro Ellipta FDA Label Archive. AccessData. FDA.govHistorical label revision documenting updated warnings and safety data including IMPACT trial cardiovascular outcomes.
- Decramer M, Anzueto A, Kerwin E, et al. Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials. Lancet Respir Med. 2014;2(6):472-486. doi:10.1016/S2213-2600(14)70065-7Pivotal Trial 1 and Trial 2 demonstrating superiority of UMEC/VI over individual components and tiotropium in trough FEV1 improvement.
- Maleki-Yazdi MR, Kaelin T, Richard N, et al. Efficacy and safety of umeclidinium/vilanterol 62.5/25 mcg and tiotropium 18 mcg in chronic obstructive pulmonary disease: results of a 24-week, randomized, controlled trial. Respir Med. 2014;108(12):1752-1760. doi:10.1016/j.rmed.2014.10.002Head-to-head trial vs tiotropium showing non-inferior to superior trough FEV1 with UMEC/VI; contributed to the four 6-month trial pooled safety data.
- Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD (IMPACT). N Engl J Med. 2018;378(18):1671-1680. doi:10.1056/NEJMoa171390152-week trial including UMEC/VI arm (n=2,070); source of MACE rate and pneumonia advantage data (5% vs 8% triple therapy).
- Feldman GJ, Sousa AR, Lipson DA, et al. Comparative efficacy of umeclidinium/vilanterol and tiotropium/olodaterol in symptomatic COPD: a randomized trial. Adv Ther. 2017;34(11):2518-2533. doi:10.1007/s12325-017-0626-4Head-to-head crossover trial vs STIOLTO showing superiority of UMEC/VI in trough FEV1 at 8 weeks.
- Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Prevention, Diagnosis and Management of COPD, 2024 Report. goldcopd.orgPositions LAMA/LABA dual bronchodilator therapy as first-line for symptomatic COPD patients (Group B/E without high eosinophils).
- Salmon M, Luttmann MA, Foley JJ, et al. Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013;345(2):260-270. doi:10.1124/jpet.112.202051Characterises umeclidinium’s prolonged M3 receptor antagonism and >24-hour bronchodilatory effect.
- Slack RJ, Barrett VJ, Morrison VS, et al. In vitro pharmacological characterization of vilanterol, a novel long-acting beta2-adrenoceptor agonist with 24-hour duration of action. J Pharmacol Exp Ther. 2013;344(1):218-230. doi:10.1124/jpet.112.198481Establishes vilanterol’s 24-hour duration of action and beta-2 receptor selectivity, supporting once-daily dosing.
- Cazzola M, Molimard M. The scientific rationale for combining long-acting beta2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther. 2010;23(4):257-267. doi:10.1016/j.pupt.2010.03.003Reviews the mechanistic rationale for LAMA/LABA combination, explaining additive bronchodilation through distinct cholinergic and adrenergic pathways.
- Mehta R, Engel M, Engel B, et al. Population pharmacokinetic analysis of umeclidinium and vilanterol in patients with chronic obstructive pulmonary disease. Clin Pharmacokinet. 2017;56(8):943-953. doi:10.1007/s40262-016-0486-yPopulation PK analysis confirming that age, race, gender, and CYP2D6 metaboliser status do not clinically alter UMEC or VI exposure.