General

Pronunciation:
floo-tik-a-sone/ue-mek-li-din-ee-um/vye-lan-ter-ol

Trade Name(s)

• Trelegy Ellipta

Ther. Class.
bronchodilators

Pharm. Class.
corticosteroids
anticholinergics
adrenergics

Indications

Maintenance treatment of COPD.

Action

 Fluticasone– decreases airway inflammation umeclidinium– acts as an anticholinergic by inhibiting M3 muscarinic receptors in bronchial smooth muscle resulting in bronchodilation vilanterol– beta₂ -adrenergic agonist that stimulates adenyl cyclase, resulting in accumulation of cyclic adenosine monophosphate and subsequent bronchodilation.

Therapeutic Effect(s):

Improved airflow and ↓ exacerbations in COPD.

Pharmacokinetics

Absorption:  Fluticasone– 15.2% systemically absorbed from lungs following inhalation; minimal absorption from swallowing;  umeclidinium– mostly absorbed from lungs; minimal oral absorption;  vilanterol– mostly absorbed from lungs; minimal oral absorption.

Distribution: Unknown.

Protein Binding:  Fluticasone– >99%,  vilanterol– 94%.

Metabolism and Excretion:  Fluticasone– primarily metabolized by CYP3A4 to inactive metabolites; parent drug and metabolites excreted primarily in feces, 1–2% excreted in urine;  umeclidinium– primarily metabolized by CYP2D6 to inactive metabolites; parent drug and metabolites excreted in feces (58%) and urine (22%);  vilanterol– primarily metabolized by CYP3A4 to inactive metabolites; parent drug and metabolites excreted in urine (70%) and feces (30%).

Half-life:  Fluticasone– 24 hr;  umeclidinium– 11 hr;  vilanterol– 11 hr.

TIME/ACTION PROFILE (bronchodilation)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to any components or severe hypersensitivity to milk proteins;
• Asthma;
• Acute attack of COPD (onset of action is delayed).

Use Cautiously in:

• Active untreated infections;
• Cardiovascular disease;
• Prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of anticonvulsants or oral corticosteroids (↑ risk of ↓ bone mineral density);
• Narrow-angle glaucoma (may cause acute angle closure);
• Cataracts
• Urinary retention, prostatic hyperplasia, bladder-neck obstruction;
• History of seizures, thyrotoxicosis, diabetes mellitus, or ketacidosis;
• Hepatic or renal impairment;
• OB:   Safety not established
• Lactation: Use while breastfeeding only if maternal benefit outweighs potential risk to infant;
• Pedi:  Safety and effectiveness not established;
• Geri:  May be more sensitive to drug effects.

Exercise Extreme Caution in:

Concurrent use of MAOIs, tricyclic antidepressants, or QTc interval prolonging drugs.

Adverse Reactions/Side Effects

CNS: headache

CV: ARRHYTHMIAS, hypertension, QTc interval prolongation, tachycardia

EENT: cataracts, dysphonia, glaucoma, oral candidiasis

Endo: adrenal suppression, hyperglycemia

F and E: hypokalemia

GI: constipation, diarrhea, metallic taste

GU: urinary retention

MS: arthralgia, back pain, ↓ bone mineral density

Resp: ↑ risk of pneumonia, paradoxical bronchospasm

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• CYP3A4 inhibitors, including clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, or  voriconazole  may ↑ fluticasone and vilanterol levels and the risk of corticosteroid effects or adverse cardiovascular reactions; concurrent use should be undertaken with caution.
• Concurrent use with MAO inhibitors, tricyclic antidepressants, or  QTc interval prolonging drugs  ↑ risk of cardiovascular reactions from vilanterol; exercise extreme caution when considering concurrent use or use within 2 wk of discontinuing above drugs.
• Concurrent use of  beta-blockers  may ↓ effectiveness of vilanterol and ↑ risk of severe bronchospasm; consider use of cardioselective beta-blocker.
• ↑ risk of hypokalemia with concurrent use of  loop diuretics  or  thiazide diuretics .
• ↑ risk of anticholinergic adverse reactions when used concurrently with other  anticholinergics ; avoid concurrent use.

Route/Dosage

Inhaln  (Adults)  One inhalation (fluticasone 100 mcg/umeclidinium 62.5 mcg/vilanterol 25 mcg) once daily.

Availability

Powder for inhalation (contains lactose): fluticasone 100 mcg/umeclidinium 62.5 mcg/vilanterol 25 mcg in a two-strip blister per dose

Assessment

• Monitor respiratory status and lung sounds. Assess pulmonary function tests periodically during and for several mo after a transfer from systemic to inhalation corticosteroids.
• Monitor for signs and symptoms of hypersensitivity reactions (rash, pruritis, swelling of face and neck, dyspnea) periodically during therapy.
• Monitor ECG BP, and pulse rate periodically during therapy. May cause ↑ pulse, ↑BP, prolonged QTc interval, ST segment depression, supraventricular tachycardia, and extra systoles.
• Observe for paradoxical bronchospasm (wheezing, dyspnea, tightness in chest) and hypersensitivity reaction (rash; urticaria; swelling of the face, lips, or eyelids). If condition occurs, withhold medication and notify health care professional immediately.
• Assess patients changing from systemic corticosteroids to inhalation corticosteroids for signs of adrenal insufficiency (anorexia, nausea, weakness, fatigue, hypotension, hypoglycemia) during initial therapy and periods of stress. If these signs appear, notify health care professional immediately; condition may be life-threatening.
• Monitor for withdrawal symptoms (joint or muscular pain, lassitude, depression) during withdrawal from oral corticosteroids.
• May cause decreased bone mineral density during prolonged therapy. Monitor patients with increased risk (prolonged immobilization, family history of osteoporosis, post-menopausal status, tobacco use, advanced age, poor nutrition, chronic use of drugs that can reduce bone mass [anticonvulsants, oral corticosteroids]) for fractures.

Lab Test Considerations:

May cause hypokalemia and hyperglycemia.

Potential Diagnoses

• Ineffective airway clearance (Indications) 

Implementation

• Inhaln  Administer once daily at the same time each day. Do not open cover of inhaler until you are ready to use it. If cover is closed before use, dose will be lost. Close cover after medication is inhaled. Discard dessicant; do not eat or inhale. Discard inhaler 6 wk after opening; inhaler is not reusable.
• After inhalation, rinse mouth with water without swallowing to help reduce risk of oropharyngeal candidiasis.

Patient/Family Teaching

• Advise patient to take medication as directed. If a dose is missed, take as soon as remembered unless almost time for next dose. Instruct patient to read the  Patient Information and Instructions for Use  before using and with each Rx refill, in case of new information. Advise patient not to discontinue medication without consulting health care professional; gradual decrease is required.
• Caution patient not to use medication to treat acute symptoms. A rapid-acting inhaled beta-adrenergic bronchodilator should be used for relief of acute asthma attacks. Notify health care professional immediately if symptoms get worse or more inhalations than usual are needed from rescue inhaler.
• Advise patient to stop using medication and notify health care professional immediately if signs and symptoms of hypersensitivity reactions occur.
• Instruct patient not to use additional long-acting Beta₂ -agonists.
• Caution patient to avoid smoking, known allergens, and other respiratory irritants.
• Advise patient to notify health care professional if signs and symptoms of pneumonia (fever, chills, shortness of breath, increased cough, increased sputum production or change in mucus color), urinary retention (difficulty passing urine, painful urination), sore throat or mouth occur.
• Instruct patient to notify health care professional immediately if exposed chickenpox or measles. Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking other Rx, OTC, or herbal products.
• Advise patient to have regular eye examinations; may increase risk of cataracts and glaucoma. Instruct patient to notify health care professional immediately if signs and symptoms of glaucoma (eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion corneal edema) occur.
• Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Improved airflow and ↓ exacerbations in COPD.