vilanterol/fluticasone furoate inhaled (Breo Ellipta)

Dosing and uses of Breo Ellipta (vilanterol fluticasone inhaled)

• Adult
• Pediatric

 

Adult dosage forms and strengths

vilanterol/fluticasone furoate inhaled

powder for inhalation

• 25mcg/100mcg per actuation
• 25mg/200mcg per actuation
• Ellipta inhaler contains 2 double-foil blister strips, 1 containing fluticasone furoate and the other strip contains vilanterol; after the inhaler is activated, the powder within both blisters is exposed and ready for dispersion

 

Chronic Obstructive Pulmonary Disease

Indicated for long-term, once-daily, maintenance treatment of airflow obstruction with COPD, including chronic bronchitis and/or emphysema; also approved to reduce COPD exacerbations

25 mcg/100 mcg (1 actuation) inhaled PO qDay

 

Asthma

Indicated for once-daily treatment of asthma for patients not adequately controlled on a long-term asthma control medication (eg, inhaled corticosteroid), or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a long-acting beta agonist (LABA)

Use prescribe strength (25 mcg/100 mcg or 25 mcg/200 mcg per actuation) once daily via oral inhalation

 

Dosage modifications

Hepatic or renal impairment: No dosage adjustment required

Geriatric patients: No dosage adjustment required

 

Dosing Considerations

Limitations of use: NOT indicated for the relief of acute bronchospasm

Asthma indication

• LABAs (eg, vilanterol) increase the risk of asthma-related death
• Available data from controlled clinical trials suggest that LABAs increase the risk of asthma-related hospitalization in pediatric and adolescent patients
• Therefore, when treating patients with asthma, physicians should only prescribe vilanterol/fluticasone furoate inhaled for patients not adequately controlled on a long-term asthma control medication (eg, inhaled corticosteroid), or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA
• Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (eg, discontinue vilanterol/fluticasone furoate inhaled) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication (eg, inhaled corticosteroid)
• Do not use for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Breo Ellipta (vilanterol fluticasone inhaled) adverse (side) effects

1-10%

Nasopharyngitis (9%)

Upper respiratory infection (7%)

Headache (7%)

Oropharyngeal candidiasis (5%)

 

Postmarketing reports

Anxiety

Tremors

Palpitations, tachycardia

Anaphylaxis, angioedema, rash, urticaria

Muscle spasms

Tremor

Nervousness

 

Warnings

Black box warnings

Long-acting beta2-adrenergic agonists (LABAs), such as vilanterol, increase the risk for asthma-related death

A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths; this finding is considered a class effect of all LABA, including vilanteroL

Therefore, when treating patients with asthma, physicians should only prescribe vilanterol/fluticasone furoate inhaled for patients not adequately controlled on a long-term asthma control medication (eg, inhaled corticosteroid), or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA

Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (eg, discontinue vilanterol/fluticasone furoate inhaled) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication (eg, inhaled corticosteroid)

Do not use for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids

 

Contraindications

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

Hypersensitivity to drug, any components/excipients, or milk proteins

 

Cautions

LABAs (eg, vilanterol) increase the risk of asthma-related death (see Black box warnings)

Increasing use of inhaled, short-acting beta2-agonists (ie, rescue inhalers) is a marker of deteriorating disease and acute episodes; reevaluate the patient immediately

Do not initiate during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy acute bronchospasm, which should be treated with an inhaled, short-acting beta2-agonist LABAs increase asthma-related death (see Black box warnings)

Do not use in combination with another medication containing a LABA because of risk for overdose

Caution with underlying cardiovascular disease because of beta-adrenergic stimulation

Risk of paradoxical bronchospasm, which may be life-threatening; discontinue and treat immediately with inhaled SABA

Decreases bone mineral density following long-term administration of corticosteroids; bone fractures reported with inhaled corticosteroid use; assess upon initiation and periodically thereafter

Corticosteroids increase risk of pneumonia; monitor for S/S of pneumonia and lung infections

Corticosteroids increase risk of cataracts, glaucoma, and increased IOP Excessive use (or at regular dose in susceptible individuals) may result in hypercorticism and suppress HPA function; monitor closely, especially postoperatively or during periods of stress

Corticosteroids increase risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex

Risk for more serious or fatal course of chickenpox or measles in susceptible patients (eg, unvaccinated or immunologically unexposed individuals); care must be taken to avoid exposure to corticosteroids

Particular care is needed to transfer patients from systemic to inhaled corticosteroids; potentially fatal adrenal insufficiency may occur before/after; taper withdrawal gradually by reducing daily prednisone dose by 2.5 mg on weekly basis

Risk of hypokalemia and hyperglycemia

Caution with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis

Close monitoring for glaucoma and cataracts is warranted

Angioedema, rash, or urticaria may occur after administration

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Unknown whether distributed in human breast milk

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Breo Ellipta (vilanterol fluticasone inhaled)

Mechanism of action

Vilanterol: Long-acting selective beta2-adrenergic agonist (LABA); stimulates intracellular adenyl cyclase resulting in increased cAMP levels causing bronchial smooth muscle relaxation; also inhibits release of mediators of immediate hypersensitivity from cells, especially from mast cells

Fluticasone furoate (FF): Long-acting inhaled trifluorinated corticosteroid with potent anti-inflammatory activity; inhibits multiple cell types (eg, mast cells, eosinophils, basophils, lymphocytes, macrophages, neutrophils) and mediator production or secretion (eg, histamine, eicosanoids, leukotrienes, cytokines) involved in the asthmatic response

Fluticasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate

 

Absorption

Bioavailability: 27.3% (vilanterol); 15.2% (FF)

Peak plasma time: 10 minutes (vilanterol); 0.5-1 hr (FF)

AUC: 46% lower in patients with COPD compared with healthy individuals

 

Distribution

Following IV administration of each component

Protein bound: 93.9% (vilanterol); 99.6% (FF)

Vd: 165 L (vilanterol); 661 L (FF)

 

Metabolism

Vilanterol is mainly metabolized, principally via CYP3A4, to a range of metabolites with significantly reduced beta1- and beta2-agonist activity

Fluticasone furoate is cleared from systemic circulation principally by hepatic metabolism via CYP3A4 to metabolites with significantly reduced corticosteroid activity

 

Elimination

Half-life: 21.3 hr (vilanterol); 24 hr (FF)

Excretion

• Pharmacokinetic studies following oral and IV administration
• Vilanterol and metabolites: 30% feces; 70% urine
• Fluticasone furoate and metabolites: 90-100% feces; 1-2% urine

 

Administration

Instructions

After inhalation, rinse mouth with water and expectorate to help reduce risk of oropharyngeal candidiasis

Take at same time each day

Do not exceed 1 administration/24 hr

More frequent administration or a greater number of inhalations (>1 inhalation daily) of the prescribed strength is not recommended as some patients are more likely to experience adverse effects with higher doses

Patients should not use an additional long-acting beta agonist (LABA) for any reason