Fluticasone, Umeclidinium, and Vilanterol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol Powder Breath Activated, Inhalation:

Trelegy Ellipta: Fluticasone furoate 100 mcg, umeclidinium 62.5 mcg, and vilanterol 25 mcg (28 ea, 60 ea) [contains lactose monohydrate]

Pharmacology

Mechanism of Action

Fluticasone: A corticosteroid with anti-inflammatory activity, immunosuppressive properties, and antiproliferative actions.

Umeclidinium: Competitively and reversibly inhibits the action of acetylcholine at type 3 muscarinic (M₃) receptors in bronchial smooth muscle causing bronchodilation.

Vilanterol: A long-acting beta-2 agonist, relaxes bronchial smooth muscle by selective action on beta-2 receptors with little effect on heart rate.

Use: Labeled Indications

Chronic obstructive pulmonary disease: Maintenance treatment of chronic obstructive pulmonary disease.

Limitations of use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma

Contraindications

Hypersensitivity to fluticasone, umeclidinium, vilanterol, or any component of the formulation; severe hypersensitivity to milk proteins

Dosage and Administration

Dosing: Adult

Chronic obstructive pulmonary disease: Oral inhalation: Dry powder inhaler: One inhalation (fluticasone furoate 100 mcg/umeclidinium 62.5 mcg/vilanterol 25 mcg) once daily (maximum dose: 1 inhalation/day)

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral inhalation: Dry powder inhaler: For oral inhalation only; administer at the same time each day. Discard device 6 weeks after it is removed from the foil tray or when the dose counter reads “0” (whichever comes first). Do not open the cover of the inhaler until ready for use; each time cover is opened, 1 dose of medicine is prepared. Exhale fully before taking one long, steady, deep breath through the mouthpiece (do not breathe through nose); hold breath for 3 to 4 seconds and exhale slowly and gently. Following administration, rinse mouth with water after use (do not swallow). If mouthpiece needs cleaning, wipe with a dry tissue.

Storage

Store between 20°C and 25°C (68°F and 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F). Store in a dry place away from direct heat or sunlight. Store inside the unopened moisture-protective foil tray and only remove from the tray immediately before initial use. Discard 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.

Drug Interactions

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Amphotericin B: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy

Anticholinergic Agents: Umeclidinium may enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Cobicistat: May increase the serum concentration of Fluticasone (Oral Inhalation). Avoid combination

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy

Cosyntropin: Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin. Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Fluticasone (Oral Inhalation). Management: Use of orally inhaled fluticasone propionate with strong CYP3A4 inhibitors is not recommended. Use of orally inhaled fluticasone furoate with strong CYP3A4 inhibitors should be done with caution. Monitor patients using such a combination more closely. Consider therapy modification

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. Avoid combination

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loop Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Methacholine: Beta2-Agonists (Long-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting beta₂ agonists for 36 hours before methacholine use. Consider therapy modification

Methacholine: Long-acting muscarinic antagonists (LAMAs) may diminish the therapeutic effect of Methacholine. Consider therapy modification

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Avoid combination

Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Tipranavir: May increase the serum concentration of Fluticasone (Oral Inhalation). Avoid combination

Tobacco (Smoked): May diminish the therapeutic effect of Corticosteroids (Orally Inhaled). Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Adverse Reactions

Also see Fluticasone and Umeclidinium monographs.

1% to 10%:

Central nervous system: Headache (4%), voice disorder (≥1%)

Gastrointestinal: Diarrhea (2%), dysgeusia (2%), constipation (≥1%), oral candidiasis (≥1%), gastroenteritis (1%)

Genitourinary: Urinary tract infection (≥1%)

Infection: Influenza (≥1%)

Neuromuscular & skeletal: Back pain (4%), arthralgia (≥1%)

Respiratory: Pneumonia (8%), bronchitis (≥1%), pharyngitis (≥1%), rhinitis (≥1%), sinusitis (≥1%), upper respiratory tract infection (≥1%), cough (1%), oropharyngeal pain (1%)

Frequency not defined:

Respiratory: Paradoxical bronchospasm

<1%, postmarketing, and/or case reports: Anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: Fluticasone may cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, including adrenal crisis, in patients sensitive to these effects. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled corticosteroids; deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic steroids to a less systemically available inhaled corticosteroid. Patients receiving ≥20 mg/day of prednisone (or equivalent) may be most susceptible. Fluticasone/umeclidinium/vilanterol does not provide the systemic steroid dose needed to treat patients having trauma, surgery, or infections. Select surgical patients on long-term, high-dose, inhaled corticosteroid (ICS), should be given stress doses of hydrocortisone intravenously during the surgical period and the dose reduced rapidly within 24 hours after surgery (NAEPP 2007).
• Asthma-related deaths: The use of long-acting beta-2 agonists (LABAs) as monotherapy is associated with an increased risk of asthma-related deaths. In a large, randomized, placebo-controlled US trial, salmeterol was associated with an increase in asthma-related deaths (SMART 2006); risk is considered a class effect of LABA monotherapy. Additional data from other clinical trials suggest LABA monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. However, data from large randomized, double-blind, active-controlled trials do not show a significant increase in the risk of serious asthma-related events (including hospitalizations, intubations, and death) in adult, adolescent, and pediatric (aged 4 to 11 years) patients when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy. In addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). Current guidelines recommend the use of an inhaled corticosteroid before adding a LABA (GINA 2018; NIH/NHLBI 2007). Assess patients at regular intervals once asthma control is maintained on combination therapy to determine if step-down therapy is appropriate (without loss of asthma control), and the patient can be maintained on an inhaled corticosteroid only. LABAs are not appropriate in patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids. A similar increase in the risk of death associated with LABAs has not been demonstrated in patients with COPD. Not indicated for the treatment of asthma.
• Bronchospasm: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; reaction should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue fluticasone/umeclidinium/vilanterol and institute alternative therapy
• Hypersensitivity: Hypersensitivity reactions (urticaria, angioedema, rash), including anaphylaxis may occur; discontinue if a hypersensitivity reaction occurs.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use, if possible, in patients with ocular herpes, active or quiescent tuberculosis infections of the respiratory tract; or untreated viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox or measles should be avoided; if the patient is exposed, prophylaxis with varicella zoster immune globulin or pooled intramuscular immunoglobulin, respectively, may be indicated; if chickenpox develops, treatment with antiviral agents may be considered.
• Lower respiratory infections: An increase in the incidence of pneumonia and other lower respiratory tract infections (some fatal) have been reported in patients with COPD following use; monitor COPD patients closely since pneumonia symptoms may overlap symptoms of exacerbations.
• Oral candidiasis: Local oropharyngeal Candida infections have been reported; if this occurs, treat appropriately while continuing fluticasone therapy. Patients should be instructed to rinse mouth with water without swallowing after each use.
• Serious effects/fatalities: Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.

Disease-related concerns:

• Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral content such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (eg, anticonvulsants or oral corticosteroids); long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, especially coronary insufficiency, arrhythmias, and hypertension; beta-agonists may cause elevation in blood pressure, heart rate, and increase risk of arrhythmias (eg, supraventricular tachycardia, extrasystoles); may also cause ECG changes (eg, flattening of the T wave, QTc prolongation, ST segment depression).
• Diabetes: Use with caution in patients with diabetes mellitus; beta₂-agonists may increase serum glucose and aggravate preexisting diabetes mellitus and ketoacidosis.
• Hepatic impairment: Fluticasone exposure may be increased up to threefold in patients with hepatic impairment; use with caution in patients with moderate or severe impairment and monitor closely.
• Hypokalemia: Use with caution in patients with hypokalemia; beta₂-agonists may decrease serum potassium (effect is usually transient).
• Ocular disease: Use with caution in patients with increased intraocular pressure, cataracts and/or glaucoma; increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use of inhaled corticosteroids. Consider routine eye exams in chronic users.
• Prostatic hyperplasia/bladder neck obstruction: Umeclidinium may worsen the symptoms of prostatic hyperplasia and/or bladder neck obstruction (eg, painful urination, difficulty passing urine); use with caution.
• Seizure disorders: Use with caution in patients with seizure disorders.
• Thyrotoxicosis: Use with caution in patients with thyrotoxicosis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Lactose: May contain lactose; anaphylactic reactions have been reported in patients with severe milk protein allergy using other lactose-containing powder products.

Other warnings/precautions:

• Appropriate use: Do not use for acute episodes of COPD. Do not initiate in patients with significantly worsening, potentially life-threatening, or acutely deteriorating COPD. Do not exceed the recommended dose.
• Discontinuation of systemic corticosteroids: Withdraw systemic corticosteroid therapy with gradual tapering of dose (eg, patients on prednisone may decrease dose by 2.5 mg weekly during inhaled corticosteroid therapy). Monitor lung function, beta-agonist use, and COPD symptoms, and for signs and symptoms of adrenal insufficiency (fatigue, lassitude, weakness, nausea and vomiting, hypotension) during withdrawal.
• Transfer to oral inhaler: When transferring to oral inhaler, previously suppressed allergic conditions (arthritis, rhinitis, conjunctivitis, eczema, eosinophilic conditions) may be unmasked.
• Patient information: Patients must be instructed to use short-acting beta₂-agonists (eg, albuterol) for acute COPD symptoms and to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of inhaled short-acting beta₂-agonists may indicate deterioration of COPD, and medical evaluation to assess treatment regimen must not be delayed.

Monitoring Parameters

FEV₁, peak flow, and/or other pulmonary function tests; bone mineral density (at baseline and periodically thereafter); blood pressure, heart rate; serum potassium (hypokalemic patients) and glucose (diabetic patients); ocular changes (intraocular pressure, cataracts); signs/symptoms of oral or systemic infection, hypercortisolism, or adrenal suppression

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. Refer to individual monographs.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience back pain, joint pain, flu-like symptoms, common cold symptoms, change in taste, nausea, vomiting, diarrhea, constipation, throat pain, throat irritation, mouth irritation, or mouth pain. Have patient report immediately to prescriber signs of infection, signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), severe headache, severe dizziness, passing out, vision changes, chest pain, fast heartbeat, abnormal heartbeat, anxiety, tremors, eye pain, severe eye irritation, seeing halos or bright colors around lights, difficult urination, painful urination, change in amount of urine passed, thrush, bone pain, or signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.