Fluticasone, Umeclidinium, and Vilanterol (Oral Inhalation) (Monograph)

Brand name: Trelegy Ellipta
Drug class: Adrenals

Introduction

Fixed-dose triple combination preparation containing an inhaled synthetic trifluorinated corticosteroid (fluticasone), a long-acting muscarinic antagonist (umeclidinium), and a long-acting β₂-adrenergic agonist (vilanterol).

Uses for Fluticasone, Umeclidinium, and Vilanterol (Oral Inhalation)

COPD

Used for maintenance treatment of patients with COPD. Not indicated for treatment of acute bronchospasm.

The fixed combination preparation containing 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol (fluticasone furoate/umeclidinium/vilanterol 100/62.5/25 mcg) is the only strength indicated for treatment of COPD.

Inhaled bronchodilators such as long-acting β₂-adrenergic agonists (LABA) and long-acting muscarinic antagonists (LAMA) are central to symptom management in COPD. The addition of an inhaled corticosteroid (triple therapy) may be considered in patients who require additional treatment because of ongoing symptoms and/or exacerbations despite dual therapy.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines state that therapy with a LABA, LAMA, and inhaled corticosteroid has been shown to improve lung function, patient-reported outcomes, and reduce exacerbations compared with LAMA alone, LABA plus LAMA or LABA plus an inhaled corticosteroid. Some data also suggest a possible mortality benefit of triple therapy over fixed-dose LABA and LAMA combinations in patients with symptomatic COPD who have a history of frequent and/or severe exacerbations.

Asthma

Used for maintenance treatment of asthma in adults. Not indicated for treatment of acute bronchospasm.

The Global Initiative for Asthma (GINA) guidelines provide evidence-based recommendations for the management of asthma. A stepwise approach to treatment is recommended where specific drugs are added or adjusted through a series of steps (1 through 5) to achieve symptom control while keeping the patient on the lowest effective treatment.

Fluticasone, Umeclidinium, and Vilanterol (Oral Inhalation) Dosage and Administration

General

Pretreatment Screening

• Assess bone mineral density (BMD) in patients with COPD prior to initiation of fluticasone/umeclidinium/vilanterol therapy.

Patient Monitoring

• COPD may deteriorate acutely over a period of hours or over several days or longer. Failure to respond to a previously effective dosage of fluticasone/umeclidinium/vilanterol or to a supplemental short-acting, inhaled β₂-agonist (e.g., increased need for additional short-acting, inhaled β₂-agonists) may indicate deterioration of COPD. In this setting, immediately re-evaluate the patient and treatment regimen. For COPD, the daily dose of fluticasone/umeclidinium/vilanterol 100/62.5/25 mcg should not be increased.

• Monitor for the possible development of pneumonia in patients with COPD.

• In patients with asthma, increasing use of inhaled, short-acting β₂-agonists may indicate deteriorating asthma. In this situation, re-evaluate the patient and the current treatment regimen; consider the possible need for additional therapeutic options. Patients should not use more than 1 inhalation once daily of fluticasone/umeclidinium/vilanterol.

• In patients being switched from systemic corticosteroids to orally inhaled fluticasone/umeclidinium/vilanterol, withdraw the systemic corticosteroid therapy gradually and monitor patients for signs and symptoms of adrenal insufficiency (e.g., hypotension, fatigue, lassitude, weakness, nausea, vomiting). Also monitor lung function (FEV₁ or peak expiratory flow), adjunctive β₂-adrenergic agonist use, and COPD/asthma symptoms carefully during withdrawal of systemic corticosteroid therapy.

• Because of the possibility of significant systemic absorption of inhaled corticosteroids, observe patients carefully for any evidence of systemic effects especially during the postoperative period or periods of stress.

• Monitor patients with major risk factors for decreased BMD (e.g., prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, chronic use of drugs that can decrease bone mass) and treat according to established standards of care. Assess BMD in patients with COPD periodically during therapy.

• Monitor patients for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), especially those with prostatic hyperplasia or bladder-neck obstruction.

• Monitor patients for signs and symptoms of acute narrow angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema).

• Since this product contains fluticasone, monitor patients periodically for localized fungal infections of the mouth and pharynx.

Administration

Oral Inhalation

Administer by oral inhalation once daily using a disposable inhaler that delivers powdered fluticasone, umeclidinium, and vilanterol in fixed combination from foil-wrapped blisters.

Administer at the same time every day and do not use more than once every 24 hours.

Prior to use, store in the original foil tray at room temperature in a dry place away from direct heat and sunlight; remove from tray immediately before initial use.

Document the date the tray is opened and the discard date (6 weeks after opening) on the inhaler label.

The number of doses remaining in the inhaler is displayed on the counter.

Before inhaling dose, exhale completely; do not exhale into mouthpiece of inhaler. Place mouthpiece between lips and inhale deeply through inhaler with a steady, even breath; do not inhale through nose. Remove inhaler from mouth, hold the breath for about 3–4 seconds (or as long as comfortable), then exhale slowly and gently.

Do not administer another dose even if delivery of dose not perceived.

Routine cleaning of inhaler is not necessary; may clean mouthpiece with dry tissue if desired.

If a dose is missed, take it as soon as it is remembered. Do not take more than 1 inhalation per day and take the next dose at the usual time.

Dosage

Dosage of fluticasone furoate is expressed in terms of the furoate salt. Dosage of umeclidinium bromide is expressed in terms of umeclidinium. Dosage of vilanterol trifenatate is expressed in terms of vilanterol.

Supplied with a disposable plastic inhaler containing 2 foil strips, each with 30 blisters (or 14 blisters in the institutional package). 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. Precise amount of drug delivered depends on patient factors such as inspiratory flow.

Adults

COPD

Fluticasone/Umeclidinium/Vilanterol Fixed-combination Therapy

Oral Inhalation

100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol (1 inhalation) once daily.

Do not use more than 1 time every 24 hours.

If shortness of breath occurs between doses, an inhaled, short-acting β₂-agonist (rescue medicine, e.g., albuterol) should be taken for immediate relief.

Asthma

Fluticasone/Umeclidinium/Vilanterol Fixed-combination Therapy

Oral Inhalation

Recommended starting dosage is 100 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol (1 inhalation) or 200 mcg of fluticasone furoate, 62.5 mcg of umeclidinium, and 25 mcg of vilanterol (1 inhalation) once daily.

When selecting starting dosage strength, consider patient's disease severity based on previous asthma therapy, including dosage of inhaled corticosteroids as well as patient's current control of asthma symptoms and risk of future exacerbation.

For patients who do not respond adequately to fluticasone/umeclidinium/vilanterol 100/62.5/25 mcg, increasing dose to fluticasone/umeclidinium/vilanterol 200/62.5/25 mcg may provide additional improvement in asthma control.

Fluticasone/umeclidinium/vilanterol 200/62.5/25 mcg is the maximum recommended dose; for patients who do not respond adequately to fluticasone/umeclidinium/vilanterol 200/62.5/25 mcg once daily, re-evaluate and consider other therapeutic regimens and additional therapeutic options.

Do not use more than 1 time every 24 hours.

If asthma symptoms occur between doses, administer an inhaled, short-acting β₂-agonist (rescue medicine, e.g., albuterol) for immediate relief.

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with moderate hepatic impairment; not studied in patients with severe hepatic impairment.

Renal Impairment

No dosage adjustment required in patients with renal impairment.

Geriatric Use

No dosage adjustment required.

Cautions for Fluticasone, Umeclidinium, and Vilanterol (Oral Inhalation)

Contraindications

• Primary treatment of status asthmaticus or other acute episodes of COPD or asthma where intensive measures are required.

• Severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone furoate, umeclidinium, vilanterol, or any of the excipients.

Warnings/Precautions

Serious Asthma-related Events

Increased risk of asthma-related deaths reported with long-acting β₂-adrenergic agonists (LABA) when used as monotherapy. However, when LABA used in fixed combination with inhaled corticosteroids, data from large clinical trials do not show a significant increase in risk of serious asthma-related events (hospitalizations, intubations, death) compared with use of inhaled corticosteroids alone.

Available data do not suggest an increased risk of death with use of LABA in patients with COPD.

Deterioration of Disease and Acute Episodes

Do not initiate in patients with rapidly deteriorating or potentially life-threatening episodes of COPD or asthma. Not studied in this setting.

Not studied for relief of acute symptoms; do not use extra doses in such situations. Use a short-acting, inhaled β₂-agonist as needed for acute symptoms.

When initiating therapy, discontinue regular use of short-acting oral or inhaled β₂-agonists and use only for relief of acute symptoms.

Failure to respond to a previously effective dosage of fluticasone/umeclidinium/vilanterol or to a supplemental short-acting, inhaled β₂-agonist may indicate worsening COPD. Immediately reevaluate the patient and treatment regimen. Do not increase the daily dose of fluticasone/umeclidinium/vilanterol in this situation.

Excessive Use and Use with Other Long-acting β2-Adrenergic Agonists

Clinically important cardiovascular effects and fatalities reported with excessive use of inhaled sympathomimetic drugs.

Do not use more frequently or at dosages higher than recommended or concomitantly with other preparations containing LABAs, since overdosage may result.

Local Effects of Inhaled Corticosteroids

Localized infections of the mouth and pharynx with Candida albicans reported. If such an infection develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while continuing treatment with fluticasone/umeclidinium/vilanterol, but therapy may need to be interrupted.

Advise patient to rinse his/her mouth with water without swallowing following inhalation to help reduce risk of oropharyngeal candidiasis.

Pneumonia

Increased incidence of pneumonia, sometimes resulting in hospitalization and fatality, observed in patients with COPD receiving inhaled corticosteroids.

Monitor for possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations.

Immunosuppression

Increased susceptibility to infections in patients who are taking immunosuppressant drugs (e.g., corticosteroids) compared with healthy individuals. Certain infections (e.g., chickenpox, measles) can have a more serious or even fatal outcome in such patients.

Take particular care to avoid exposure in susceptible patients.

If exposure to chickenpox or measles occurs in susceptible patients, consider administering varicella zoster immune globulin (VZIG) or pooled immune globulin (IG), respectively.

Consider treatment with an antiviral agent if chickenpox develops.

Use inhaled corticosteroids with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Withdrawal of Systemic Corticosteroid Therapy

Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids; deaths due to adrenal insufficiency occurred in patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.

Withdraw systemic corticosteroid therapy gradually and monitor for objective signs of adrenal insufficiency (e.g., fatigue, lassitude, weakness, nausea, vomiting, hypotension). Also carefully monitor lung function (FEV₁ or peak expiratory flow), adjunctive β₂ -adrenergic agonist use, and COPD/asthma symptoms.

Patients who have been maintained on 20 mg or more of prednisone (or its equivalent) daily may be most susceptible to such adverse events, particularly during the later part of the withdrawal process.

Corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression) may occur.

Monitor carefully for acute adrenal insufficiency during exposure to trauma, surgery, or infection (particularly gastroenteritis or other conditions associated with acute electrolyte loss).

Unmasking of conditions previously controlled by systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions) may occur.

Hypercorticism and Adrenal Suppression

Administration of higher than recommended dosages of orally inhaled fluticasone may result in manifestations of hypercorticism and suppression of HPA function. If such changes occur, reduce fluticasone/umeclidinium/vilanterol slowly, consistent with accepted procedures for reducing corticosteroid dosage and management of COPD or asthma symptoms.

Take particular care in monitoring patients postoperatively or during periods of stress for evidence of inadequate adrenal response.

Drug Interactions with Strong CYP3A4 Inhibitors

Use caution when considering concomitant administration of fluticasone/umeclidinium/vilanterol with ketoconazole and other strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole); increased cardiovascular adverse effects and systemic corticosteroid steroid effects may occur.

Paradoxical Bronchospasm

Possible life-threatening paradoxical bronchospasm may occur.

If paradoxical bronchospasm occurs, treat patient immediately with an inhaled, short-acting bronchodilator. Discontinue fluticasone/umeclidinium/vilanterol immediately and institute alternative therapy.

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, rash, urticaria) may occur. Discontinue if such reactions occur.

Anaphylactic reactions reported in patients with severe milk protein allergy following oral inhalation of powder products containing lactose; fluticasone/umeclidinium/vilanterol is contraindicated in patients with severe hypersensitivity to milk proteins.

Cardiovascular Effects

Possible increases in pulse rate, systolic or diastolic BP, or cardiac arrhythmias (e.g., supraventricular tachycardia, extrasystoles). If such effects occur, discontinuance of fluticasone/umeclidinium/vilanterol therapy may be required.

ECG changes (e.g., flattening of T wave, prolongation of QT_c interval, ST-segment depression) reported with β₂-agonists; clinical importance unknown.

Use fluticasone/umeclidinium/vilanterol with caution in patients with cardiovascular disorders (e.g., coronary insufficiency, cardiac arrhythmias, hypertension).

Reduction in Bone Mineral Density

Long-term use of orally inhaled corticosteroids may result in a loss of BMD. Clinical importance of small changes in BMD with regard to long-term consequences such as fracture unknown.

Monitor and treat patients with major risk factors for decreased BMD (e.g., prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, chronic use of drugs that can decrease bone mass) according to standards of care.

In patients with COPD, assess BMD prior to initiation of fluticasone/umeclidinium/vilanterol therapy and periodically thereafter. If appreciable reductions in BMD occur and use of fluticasone/umeclidinium/vilanterol is considered to be medically important for the patient’s COPD therapy, strongly consider use of agents to treat or prevent osteoporosis.

Worsening of Narrow-angle Glaucoma

Use caution in patients with narrow-angle glaucoma.

Monitor patients for signs and symptoms of acute narrow angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a healthcare provider immediately if any of these signs or symptoms develop.

Worsening of Urinary Retention

Use caution in patients with urinary retention.

Monitor patients for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), especially in those with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a healthcare provider immediately if any of these signs or symptoms develop.

Comorbid Conditions

Use with caution in patients with convulsive disorders or thyrotoxicosis, and those who are unusually responsive to sympathomimetic amines.

IV albuterol (IV preparation not commercially available in the US) reported to aggravate preexisting diabetes mellitus and ketoacidosis.

Hypokalemia and Hyperglycemia

Increased blood glucose levels reported in patients receiving beta-adrenergic agonist therapies.

Clinically important hypokalemia may occur in some patients receiving β₂-adrenergic agonists. Usually transient and does not require supplementation.

Effects on Growth

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children and adolescents.

Specific Populations

Pregnancy

Insufficient data in pregnant women to inform a drug associated risk.

In animal reproduction studies, no adverse developmental effects observed with individual components.

Women with poorly or moderately controlled asthma have increased risk of perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Closely monitor pregnant women and adjust medications as necessary to maintain optimal control of asthma.

Use during late gestation and labor only if potential benefit justifies potential for risks related to beta-agonists interfering with uterine contractility.

Lactation

No information available on the presence of fluticasone furoate, umeclidinium, or vilanterol in human milk; the effects on the breastfed child or on milk production also not known. Consider developmental and health benefits of breastfeeding along with mother's clinical need for fluticasone/umeclidinium/vilanterol and any potential adverse effects on the breastfed child from the drugs or underlying maternal condition.

Pediatric Use

Safety and effectiveness not established.

Geriatric Use

No overall differences in safety or effectiveness observed between patients ≥65 years of age and younger patients. No dosage adjustment is necessary, but greater sensitivity in some older individuals cannot be ruled out.

Hepatic Impairment

Not studied in patients with hepatic impairment.

Use with caution in patients with moderate or severe hepatic impairment and monitor patients for corticosteroid-related side effects.

Renal Impairment

Not studied in patients with renal impairment. No dosage adjustment is required.

Common Adverse Effects

Patients with COPD: Most common adverse reactions (≥1%) include 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.

Patients with asthma: Most common adverse reactions (≥2%) include 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.

Drug Interactions

Umeclidinium is metabolized primarily by CYP2D6. Fluticasone furoate and vilanterol are substrates of CYP3A4.

Fluticasone, vilanterol, and umeclidinium are all substrates of P-glycoprotein (P-gp).

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Concomitant use of fluticasone/umeclidinium/vilanterol with strong inhibitors of CYP3A4 (e.g., clarithromycin, conivaptan, ketoconazole, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) is expected to result in increased systemic exposure to vilanterol and fluticasone. Use concomitantly with caution.

Drugs that Prolong the QT Interval

Potential pharmacologic interaction (increased risk of ventricular arrhythmias and possible potentiation of vilanterol effects on cardiovascular system). Use extreme caution during concomitant therapy or within 2 weeks of discontinuance of such agents.

Specific Drugs

Fluticasone, Umeclidinium, and Vilanterol (Oral Inhalation) Pharmacokinetics

Absorption

Bioavailability

Fluticasone furoate: Peak plasma concentrations achieved within 0.5–1 hour. Absolute bioavailability of orally inhaled drug is approximately 15%, principally due to absorption of the inhaled portion of the dose delivered to the lungs. Oral bioavailability of the swallowed portion of an inhaled dose is low (approximately 1.3%) because of extensive first-pass metabolism.

Umeclidinium: Exhibits linear pharmacokinetics over dose range of 62.5–500 mcg. Steady-state plasma concentrations achieved within 14 days, with up to 1.8-fold accumulation following repeated once-daily inhalation. Peak plasma concentrations are reached within 5–15 minutes following oral inhalation.

Vilanterol: Exhibits linear pharmacokinetics over dose range of 25–100 mcg. Steady-state plasma concentrations achieved within 14 days of repeated once-daily inhalation; up to 1.7-fold accumulation observed. Peak plasma concentrations are reached within 5–15 minutes following oral inhalation.

Distribution

Plasma Protein Binding

Fluticasone furoate: >99%.

Umeclidinium: Approximately 89%.

Vilanterol: Approximately 94%.

Elimination

Metabolism

Fluticasone furoate: Eliminated principally by CYP3A4 to metabolites with significantly reduced corticosteroid activity.

Umeclidinium: Metabolized primarily by CYP2D6. Principal routes of metabolism are oxidation via hydroxylation and O-dealkylation followed by conjugation (e.g., glucuronidation).

Vilanterol: Extensively metabolized, principally by CYP3A4, to metabolites with substantially reduced β₁ and β₂-agonist activity compared with parent drug.

Elimination Route

Fluticasone furoate: Eliminated primarily in feces.

Umeclidinium: Undergoes biliary elimination (58% and 22% of a radiolabeled IV dose is recovered in feces and urine, respectively). Following oral administration, 92% and <1% of a radiolabeled dose is excreted in feces and urine, respectively.

Vilanterol: Following oral administration, approximately 70 and 30% of a radiolabeled dose is excreted in urine and feces, respectively, mostly as metabolites.

Half-life

Fluticasone furoate: Following repeat-dose inhaled administration, elimination half-life approximately 24 hours.

Umeclidinium: Effective half-life following once daily dosing is 11 hours.

Vilanterol: Effective half-life following once daily dosing is 11 hours.

Special Populations

Pharmacogenomics: Following repeated administration of umeclidinium, no clinically important effect was observed on exposure in poor CYP2D6 metabolizers compared with ultrarapid, extensive, and intermediate metabolizers.

No effects of age, gender, and race on umeclidinium pharmacokinetics.

Stability

Storage

Oral Inhalation

20–25°C (excursions permitted to 15–30°C); store in a dry place away from direct heat or sunlight.

Keep inhaler in sealed tray until immediately before use. Discard after 6 weeks of opening foil tray or when all blisters have been used, whichever comes first.

Actions

• Contains fluticasone, umeclidinium, and vilanterol.

• Fluticasone furoate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity.

• Umeclidinium, a synthetic quaternary ammonium antimuscarinic agent, is a long-acting, orally inhaled bronchodilator. Nonselective competitive antagonist at muscarinic (M1–M5) receptors.

• Vilanterol, a synthetic sympathomimetic amine, is a relatively selective, long-acting β₂-adrenergic agonist.

Advice to Patients

• Inform patients with asthma that long-acting β₂-adrenergic agonists (LABA) when used alone increases the risk of asthma-related hospitalization or asthma-related death. Available data show that when inhaled corticosteroids (ICS) and LABA are used together, such as with fluticasone/umeclidinium/vilanterol, there is not a significant increase in the risk of these events.

• Inform patients that fluticasone/umeclidinium/vilanterol is not meant to relieve acute symptoms of COPD or asthma and extra doses should not be used for that purpose. Advise patients to treat acute symptoms with an inhaled, short-acting β₂-adrenergic agonists such as albuterol. Provide patients with such medication and instruct them in how it should be used.

• Instruct patients to seek medical attention immediately if they experience decreasing effectiveness of inhaled, short-acting β₂-adrenergic agonists, need for more inhalations than usual of inhaled, short-acting β₂-adrenergic agonists, or a significant decrease in lung function as outlined by the physician.

• Inform patients that they should not stop taking fluticasone/umeclidinium/vilanterol without physician/provider guidance since symptoms may recur after discontinuation.

• Instruct patients not to use other LABA for COPD and asthma.

• Inform patients that localized infections with Candida albicans have occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with fluticasone/umeclidinium/vilanterol; therapy may need to be temporarily interrupted under close medical supervision. Advise patients to rinse their mouth with water without swallowing after inhalation to help reduce the risk of thrush.

• Patients with COPD have a higher risk of pneumonia; instruct them to contact their healthcare provider if they develop symptoms of pneumonia.

• Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay. Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

• Advise patients that fluticasone/umeclidinium/vilanterol may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, inform patients that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids. Patients should taper slowly from systemic corticosteroids if transferring to fluticasone/umeclidinium/vilanterol.

• As with other inhaled medicines, fluticasone/umeclidinium/vilanterol can cause paradoxical bronchospasm. If paradoxical bronchospasm occurs, instruct patients to discontinue the drug and contact their healthcare provider right away.

• Advise patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, rash, urticaria) may occur after administration of fluticasone/umeclidinium/vilanterol. Instruct patients to discontinue the combination preparation if such reactions occur. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use fluticasone/umeclidinium/vilanterol.

• Advise patients who are at increased risk for decreased bone mineral density (BMD) that use of corticosteroids may pose an additional risk.

• Advise patients that long-term use of inhaled corticosteroids may increase the risk of certain eye problems (cataracts or glaucoma); consider regular eye examinations.

• Instruct patients to be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination). Instruct patients to consult a physician immediately if any of these signs or symptoms develop.

• Inform patients of adverse effects associated with β₂-adrenergic agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness.

• Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• Trelegy vs. Breo: How does their use and cost compare?
• Trelegy vs Anoro: Which is better?
• Can you take Trelegy and Symbicort together?
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