the cardiovascular system may be potentiated.timololSerious - Use Alternative (1)timolol, vilanterol/fluticasone furoate inhaled. pharmacodynamic antagonism. Avoid or Use Alternate Drug. If a beta-blocker must be used in patients with COPD taking a beta-agonist, consider using a beta-blocker that is beta-1 selective .tipranavirMonitor Closely (1)tipranavir will increase the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Fluticasone furoate and vilanterol are both CYP3A4 substrates; coadministration with potent CYP3A4 inhibitors may increase systemic exposuretoremifeneSerious - Use Alternative (1)toremifene increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.torsemideMonitor Closely (1)vilanterol/fluticasone furoate inhaled and torsemide both decrease serum potassium. Modify Therapy/Monitor Closely. Beta-agonists may acutely worsen ECG changes and/or hypokalemia resulting from non-potassium-sparing diuretics tranylcypromineSerious - Use Alternative (1)tranylcypromine and vilanterol/fluticasone furoate inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiatedtrimipramineSerious - Use Alternative (2)trimipramine and vilanterol/fluticasone furoate inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated trimipramine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valbenazineMonitor Closely (1)valbenazine and vilanterol/fluticasone furoate inhaled both increase QTc interval. Use Caution/Monitor.vandetanibSerious - Use Alternative (1)vandetanib increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.vardenafilSerious - Use Alternative (1)vardenafil increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.vemurafenibSerious - Use Alternative (1)vemurafenib increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Fluticasone furoate and vilanterol are both CYP3A4 substrates; coadministration with potent CYP3A4 inhibitors may increase systemic exposureSerious - Use Alternative (1)voriconazole increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.vorinostatMonitor Closely (1)vorinostat increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Use Caution/Monitor. Exercise caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.ziprasidoneSerious - Use Alternative (1)ziprasidone increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated. 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 Paradoxical bronchospasm Hyperglycemia 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 Risk of LABAs used as monotherapy Use of LABAs as monotherapy (without inhaled corticosteroids) for asthma is associated with an increased risk of asthma-related death Data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patient These findings are considered a class effect of LABA monotherapy When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone Increased use of inhaled, short-acting pulmonary beta2-agonists (ie, rescue inhalers) is a marker of deteriorating disease and acute episodes; reevaluate 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 Do not use in combination with another medication containing a LABA because of risk for overdose Risk of localized infections of nose, mouth, and pharynx, including Candidal infections; must rinse mouth after inhalation to reduce risk; monitor patients periodically; when infection develops, treat with appropriate local or systemic (eg, oral) antifungal therapy while treatment inhaler therapy continues; in some cases, therapy may need to be interrupted 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 Orally inhaled corticosteroids may reduce growth velocity when administered to pediatric patients; monitor growth routinely (eg, via stadiometry); titrate dose to lowest dosage that effectively controls symptoms to minimize systemic effects An increase in the incidence of pneumonia observed in patients with COPD receiving therapy and increase resulting in hospitalization; in some incidences these pneumonia events were fatal; healthcare providers should remain vigilant for possible development of pneumonia in patients with COPD as clinical features of pneumonia and exacerbations frequently overlap Corticosteroids increase risk of cataracts, glaucoma, and increased IOP; consider referral to an ophthalmologist in patients who develop ocular symptoms or use drug long term 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 patient slowly from systemic corticosteroids Risk of hypokalemia and hyperglycemia Caution with convulsive disorders, thyrotoxicosis, diabetes mellitus and in those unusually responsive to sympathomimetic amines; increases in blood glucose levels reported; this should be considered in patients with a history of, or with risk factors for, diabetes mellitus; when administered IV, doses of related beta2- adrenoceptor agonist albuterol, reported to aggravate preexisting diabetes mellitus and ketoacidosis Angioedema, rash, or urticaria may occur after administration Pregnancy Insufficient data on effects of individual components, fluticasone furoate and vilanterol, in pregnant women to inform a drug-associated risk Disease-associated maternal and/or embryofetal risk; in women with poorly or moderately controlled asthma, there is increased risk of several perinatal outcomes such as pre-eclampsia in mother and prematurity, low birth weight, and small for gestational age in the neonate; pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma Labor and Delivery Use during late gestation and labor only if potential benefit justifies potential for risks related to beta-agonists interfering with uterine contractility Animal data Animal reproduction study, fluticasone furoate and vilanterol administered by inhalation alone or in combination to pregnant rats during period of organogenesis produced no fetal structural abnormalities The highest fluticasone furoate and vilanterol doses in this study were approximately 5 and 40 times maximum recommended human daily inhalation doses (MRHDID) of 200 and 25 mcg, respectively Lactation There is no information available on presence of fluticasone furoate or vilanterol in human milk; effects on breastfed child, or effects on milk production; low concentrations of other inhaled corticosteroids have been detected in human milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from fluticasone furoate or vilanterol or from underlying maternal conditionPregnancy 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. 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 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 BRAND FORM. UNIT PRICE PILL IMAGE Breo Ellipta inhalation- 200-25 mcg/dose aerosolBreo Ellipta inhalation- 200-25 mcg/dose aerosolBreo Ellipta inhalation- 100-25 mcg/dose aerosolBreo Ellipta inhalation- 100-25 mcg/dose aerosolCopyright © 2010 First DataBank, Inc.Print Patient Educationfluticasone furoate-vilanterol for inhalation FLUTICASONE/VILANTEROL POWDER INHALER - ORAL INHALATION (floo-TIK-a-sone/vye-LAN-ter-ol) COMMON BRAND NAME(S): Breo Ellipta USES: This medication is used to prevent and decrease symptoms (wheezing and trouble breathing) caused by asthma and ongoing lung disease (chronic obstructive pulmonary disease-COPD, including chronic bronchitis and emphysema). This inhaler contains 2 medications: fluticasone and vilanterol. Fluticasone belongs to a class of drugs known as corticosteroids. It works by reducing the swelling of the airways in the lungs to make breathing easier. Vilanterol belongs to a class of drugs known as long-acting beta agonists. It works by relaxing the muscles around the airways so that they open up and you can breathe more easily.When used alone, long-acting beta agonists (like vilanterol) may rarely increase the risk of serious (sometimes fatal) asthma-related breathing problems. However, combination inhaled corticosteroid and long-acting beta agonists, such as this product, do not increase the risk of serious asthma-related breathing problems. For asthma treatment, this product should be used when breathing problems are not well controlled with one