Fluticasone

Pharmacologic Category

Corticosteroid, Inhalant (Oral)

Dosing: Adult

Note: ArmonAir RespiClick has been discontinued in the United States for >1 year.

Note: Fluticasone furoate has a higher binding affinity for the lung glucocorticoid receptor compared to fluticasone propionate. The resulting enhanced affinity is reflected in the lower dose of fluticasone furoate compared to fluticasone propionate (Biggadike 2011; Valotis 2007). Further studies are needed to elucidate a clinical effect.

Asthma: Oral inhalation: Note: Titrate to the lowest effective dose once asthma stability is achieved. To decrease the severity or duration of an asthma exacerbation, may consider temporarily quadrupling the dose (early in the course of illness) in patients with mild to moderate asthma with a mild flare in symptoms. Reserve this approach for patients with no prior history of life-threatening asthma exacerbations, and in those with good self-management skills; return to baseline dose after normalization of symptoms or at a maximum of 14 days of the quadrupled dose (GINA 2020; McKeever 2018).

ArmonAir Digihaler (fluticasone propionate): Dry powder inhaler: Note: May increase dose after 2 weeks of therapy in patients who are not adequately controlled.

No prior treatment with inhaled corticosteroids (less severe asthma): Initial: 55 mcg twice daily; maximum: 232 mcg twice daily.

Prior treatment with inhaled corticosteroids or greater asthma severity: 55 to 232 mcg twice daily (base starting dosage on strength of previous inhaled corticosteroid and/or disease severity); maximum: 232 mcg twice daily.

ArmonAir RespiClick (fluticasone propionate): Dry powder inhaler: Note: May increase dose after 2 weeks of therapy in patients who are not adequately controlled.

No prior treatment with inhaled corticosteroids: Initial: 55 mcg twice daily; maximum: 232 mcg twice daily.

Prior treatment with inhaled corticosteroid: 55 to 232 mcg twice daily (base starting dosage on strength of previous inhaled corticosteroid and disease severity); maximum: 232 mcg twice daily.

Arnuity Ellipta (fluticasone furoate): Dry powder inhaler: Dosing based on previous asthma therapy: Note: May increase dose after 2 weeks of therapy in patients who are not adequately controlled.

No prior treatment with inhaled corticosteroids: Initial: 100 mcg once daily; maximum: 200 mcg/day.

Prior treatment with inhaled corticosteroids: Initial: 100 to 200 mcg once daily; maximum: 200 mcg/day.

Asthma guidelines:Global Initiative for Asthma guidelines (GINA 2020): Fluticasone furoate: Dry powder inhaler:

Low-dose therapy: 100 mcg/day.

High-dose therapy: 200 mcg/day.

Flovent HFA (fluticasone propionate):

US labeling: Note: Dosing based on previous asthma therapy and asthma severity. May increase dose after 2 weeks of therapy in patients who are not adequately controlled.

Metered-dose inhaler: Initial (patients with no prior inhaled corticosteroids): 88 mcg twice daily; maximum: 880 mcg twice daily.

Canadian labeling: Note: May increase dose after ~1 week of therapy in patients who are not adequately controlled.

Metered-dose inhaler:

Mild asthma: 100 to 250 mcg twice daily.

Moderate asthma: 250 to 500 mcg twice daily.

Severe asthma: 500 mcg twice daily; may increase up to 1,000 mcg twice daily in very severe patients (eg, patients using oral corticosteroids [OCS]).

Asthma guidelines:

Global Initiative for Asthma and National Asthma Education and Prevention Program guidelines (GINA 2020; NAEPP 2007): Fluticasone propionate (HFA): Metered-dose inhaler: Note: Administer in 1 to 4 inhalations/day depending on strength of inhaler.

Low-dose therapy: 88 to 250 mcg/day.

Medium-dose therapy: >250 to 500 mcg/day.

High-dose therapy: >500 mcg/day.

Flovent Diskus (fluticasone propionate):

US labeling: Note: Dosing based on previous asthma therapy and asthma severity. May increase dose after 2 weeks of therapy in patients who are not adequately controlled.

Dry powder inhaler: Initial (patients with no prior inhaled corticosteroids): 100 mcg twice daily; maximum: 1,000 mcg twice daily.

Canadian labeling: Note: May increase dose after ~1 week of therapy in patients who are not adequately controlled.

Dry powder inhaler:

Mild asthma: 100 to 250 mcg twice daily.

Moderate asthma: 250 to 500 mcg twice daily.

Severe asthma: 500 mcg twice daily; may increase up to 1,000 mcg twice daily in very severe patients (eg, patients using OCS).

Asthma guidelines:

Global Initiative for Asthma and National Asthma Education and Prevention Program guidelines (GINA 2020; NAEPP 2007): Fluticasone propionate: Dry powder inhaler: Note: Administer in 1 to 4 inhalations/day depending on strength of inhaler.

Low-dose therapy: 100 to 250 mcg/day.

Medium-dose therapy: >250 to 500 mcg/day.

High-dose therapy: >500 mcg/day.

Chronic obstructive pulmonary disease (stable) (off-label use): Fluticasone propionate: Oral inhalation: 50 to 500 mcg/day as a component of dual or triple combination therapy (GOLD 2014; GOLD 2019).

Eosinophilic esophagitis (off-label use): Oral:

Note: Individualize dose. Optimal dosing has not been established. Administer fluticasone by swallowing the accumulated liquid from an aerosol inhaler (ACG [Dellon 2013]; AGA/NASPGHAN [Furuta 2015]).

Induction therapy: 880 mcg/day of aerosolized fluticasone swallowed (not inhaled) administered in 2 divided doses (Chuang 2015; Furuta 2007; Moawad 2013; Murali 2016; Peterson 2010). Note: Duration of therapy 4 to 8 weeks followed by assessment of symptomatic response (eg, dysphagia). Once remission is achieved, the dose may be gradually lowered to an individualized maintenance level (ACG [Dellon 2013]; Furuta 2007; Hirano 2020; Peterson 2010).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Arnuity Ellipta: No dosage adjustment necessary.

ArmonAir Digihaler, ArmonAir RespiClick, Flovent Diskus, and Flovent HFA: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, fluticasone is primarily cleared in the liver and plasma levels may be increased in patients with hepatic impairment. Arnuity Ellipta product labeling indicates that systemic exposure is increased up to 3-fold. Use with caution and closely monitor.

Dosing: Pediatric

Asthma, maintenance therapy: Note: Initial dose is based on previous asthma therapy, current control, and risk of exacerbation. If adequate response is not seen after 2 weeks of initial dosage, increase dosage; once adequate control achieved, doses should be titrated to the lowest effective dose.

Flovent HFA (Fluticasone propionate):

US labeling: Metered-dose inhaler: Oral inhalation:

Children 4 to 11 years: 88 mcg twice daily.

Children ≥12 years and Adolescents: Initial: 88 mcg twice daily; may start doses above 88 mcg twice daily in poorly-controlled patients or in those who previously required higher doses of inhaled corticosteroids; maximum dose: 880 mcg twice daily.

Canadian labeling: Metered-dose inhaler: Oral inhalation:

Children <4 years: 100 mcg twice daily.

Children ≥4 years and Adolescents <16 years: 100 mcg twice daily; if lower or high doses are required, Flovent Diskus should be used to ensure the dose is 2 inhalations twice daily.

Adolescents ≥16 years:

Mild asthma: 100 to 250 mcg twice daily.

Moderate asthma: 250 to 500 mcg twice daily.

Severe asthma: 500 mcg twice daily; may increase up to 1,000 mcg twice daily in very severe patients.

Asthma guidelines:

National Asthma Education and Prevention Program guidelines (NAEPP 2007): Fluticasone propionate (HFA): Metered-dose inhaler: Note: Administer in divided doses twice daily:

"Low" dose:

Infants and Children ≤4 years: 176 mcg/day.

Children 5 to 11 years: 88 to 176 mcg/day.

Children ≥12 years and Adolescents: 88 to 264 mcg/day.

"Medium" dose:

Infants and Children ≤11 years: >176 to 352 mcg/day.

Children ≥12 years and Adolescents: >264 to 440 mcg/day.

"High" dose:

Infants and Children ≤11 years: >352 mcg/day.

Children ≥12 years and Adolescents: >440 mcg/day.

Global Initiative for Asthma Guidelines (GINA 2018): Fluticasone propionate (HFA): Metered-dose inhaler:

Children 4 to 5 years: "Low" dose: 100 mcg/day.

Children 6 to 11 years:

"Low" dose: 100 to 200 mcg/day.

"Medium" dose: >200 to 500 mcg/day.

"High" dose: >500 mcg/day.

Children ≥12 years and Adolescents:

"Low" dose: 100 to 250 mcg/day.

"Medium" dose: >250 to 500 mcg/day.

"High" dose: >500 mcg/day.

Flovent Diskus (Fluticasone propionate):

US labeling: Dry powder inhaler: Oral inhalation:

Children 4 to 11 years: Initial: 50 mcg twice daily; doses above 50 mcg twice daily may be considered in patients poorly controlled or in those who previously required higher doses of inhaled corticosteroids; maximum dose: 100 mcg twice daily.

Children ≥12 years and Adolescents: Initial: 100 mcg twice daily; doses above 100 mcg twice daily may be considered in poorly controlled patients or in those who previously required higher doses of inhaled corticosteroids; maximum dose: 1,000 mcg twice daily.

Canadian labeling: Dry powder inhaler: Oral inhalation:

Children ≥4 years and Adolescents <16 years: Initial: 100 mcg twice daily; may increase up to 200 mcg twice daily if necessary.

Adolescents ≥16 years:

Mild asthma: 100 to 250 mcg twice daily.

Moderate asthma: 250 to 500 mcg twice daily.

Severe asthma: 500 mcg twice daily; may increase up to 1,000 mcg twice daily in very severe patients.

Asthma guidelines:

National Asthma Education and Prevention Program Guidelines (NAEPP 2007): Dry powder inhaler: Note: Administer in divided doses twice daily:

Children 5 to 11 years:

"Low" dose: 100 to 200 mcg/day.

"Medium" dose: >200 to 400 mcg/day.

"High" dose: >400 mcg/day.

Children ≥12 years and Adolescents:

"Low" dose: 100 to 300 mcg/day.

"Medium" dose: >300 to 500 mcg/day.

"High" dose: >500 mcg/day.

Global Initiative for Asthma Guidelines (GINA 2018): Dry powder inhaler:

Children 6 to 11 years:

"Low" dose: 100 to 200 mcg/day.

"Medium" dose: >200 to 400 mcg/day.

“High" dose: >400 mcg/day.

Children ≥12 years and Adolescents:

"Low" dose: 100 to 250 mcg/day.

"Medium" dose: >250 to 500 mcg/day.

"High" dose: >500 mcg/day.

Arnuity Ellipta (fluticasone furoate): Dry powder inhaler: Oral inhalation:

Children 5 to 11 years: 50 mcg once daily.

Children ≥12 years and Adolescents: Initial: 100 mcg once daily; doses above 100 mcg once daily may be considered in poorly-controlled patients or in those who previously required higher doses of inhaled corticosteroids. Maximum dose: 200 mcg once daily.

Asthma guidelines: Global Initiative for Asthma Guidelines (GINA 2018): Dry powder inhaler:

Children ≥12 years and Adolescents:

"Low" dose: 100 mcg/day.

"High" dose: 200 mcg/day.

ArmonAir Digihaler, ArmonAir RespiClick (fluticasone propionate): Dry powder inhaler: Children ≥12 years and Adolescents: Oral inhalation: Dosing based on previous asthma therapy: Note: ArmonAir RespiClick discontinued in the US for >1 year.

No prior treatment with inhaled corticosteroids: Initial: 55 mcg twice daily; maximum: 232 mcg twice daily.

Prior treatment with inhaled corticosteroid: 55 mcg to 232 mcg twice daily (base starting dosage on strength of previous inhaled corticosteroid and disease severity); maximum: 232 mcg twice daily.

Asthma; mild flare, exacerbation: Limited data available:

Children ≥12 years and Adolescents with mild to moderate asthma, no prior history of life-threatening asthma exacerbations, and with good self-management skills:

It is recommended to temporarily quadruple the inhaled corticosteroid dose early in the course of a mild flare to decrease the severity of an asthma exacerbation. After symptoms stabilize or after a maximum of 14 days of quadrupled dose, whichever occurs first, patients should be returned to their baseline dose (GINA 2019). Quadrupling the inhaled corticosteroid dose has been shown to decrease the severity of an asthma exacerbation in select patients. In a randomized trial of adolescents ≥16 years and adults (n=1,871), temporarily quadrupling the inhaled corticosteroid dose when asthma control began to deteriorate resulted in fewer severe asthma exacerbations (ie, less treatment with systemic glucocorticoids or unscheduled appointments for asthma) compared to patients who maintained their inhaled corticosteroid dose (McKeever 2018). No data for quadrupling the dose in patients <16 years of age has been published. Quintupling the dose of inhaled corticosteroids (fluticasone) in children 5 to 11 years of age was not shown to reduce the rate of severe exacerbations and may have been associated with adverse effects (decreased linear growth, particularly in patients <8 years of age) (GINA 2019; Jackson 2018).

Bronchopulmonary dysplasia (BPD), treatment: Limited data available: Infants: Fluticasone propionate: Oral inhalation: Some centers have used 2 to 4 puffs (44 mcg/puff) every 12 hours via a face mask and a spacer. One trial used fixed doses administered via a spacer and neonatal anesthesia bag (into ventilator, directly into nasopharyngeal endotracheal tube, or with a face mask) in 16 former preterm neonates (GA: ≤32 weeks; PNA: 28 to 60 days); chest radiograph score was improved compared to placebo; the treatment group had increased blood pressure compared to baseline; the authors conclude that the trial results do not support the use of fluticasone in oxygen-dependent patients with moderate BPD; exact dosing cannot be replicated in the US with available products (Dugas 2005).

Body weight:

0.5 to 1.2 kg: 125 mcg every 12 hours for 3 weeks, followed by 125 mcg once daily for the 4th week.

≥1.2 kg: 250 mcg every 12 hours for 3 weeks, followed by 250 mcg once daily for the 4th week.

Eosinophilic esophagitis: Limited data available:

Note: Patients use an oral inhaler without a spacer and swallow the medication. Optimal dose and dosing regimen are not established. Studies performed using fluticasone propionate:

Induction and maintenance (short-term):

Twice-daily dosing (Butz 2014): Oral (swallowed):

Children ≥3 years and Adolescents: 220 mcg/spray: Initial: 880 mcg twice daily for 3 months; dose titrated based on response. Dosing based on a small randomized, multisite, double-blind, placebo-controlled trial comparing fluticasone (n=28, mean age: 12.2 years [range: 3.54 to 26.9 years]) to placebo in patients with eosinophilic esophagitis. Patients received fluticasone 880 mcg twice daily for 3 months. After 3 months, 77% of patients achieved full or partial response compared to placebo; in complete responders, the dose was reduced to 880 mcg once daily for 3 additional months. In those who did not respond, the starting dose was continued for another 3 months; however, there was no additional benefit observed in this group of patients.

Four-times-daily dosing (Schaefer 2008): Oral (swallowed):

Children ≤10 years: 110 mcg/spray: Initial: 220 mcg 4 times daily for 4 weeks, then taper over the next 8 weeks as follows: 220 mcg 3 times daily for 3 weeks, 220 mcg twice daily for 3 weeks, 220 mcg daily for 2 weeks.

Children ≥11 years and Adolescents: 220 mcg/spray: Initial: 440 mcg 4 times daily for 4 weeks, then taper over the next 8 weeks as follows: 440 mcg 3 times daily for 3 weeks, 440 mcg twice daily for 3 weeks, 440 mcg daily for 2 weeks.

Maintenance (long-term):

Twice-daily dosing (Andreae 2016; Teitelbaum 2002): Oral (swallowed):

Children 2 to 4 years: 44 mcg/spray: 88 mcg twice daily.

Children 5 to 10 years: 110 mcg/spray: 220 mcg twice daily.

Children ≥11 years and Adolescents: 220 mcg/spray: 440 mcg twice daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

Inhalation:

Arnuity Ellipta (Fluticasone furoate): Children ≥5 years and Adolescents: No dosage adjustment necessary.

ArmonAir Digihaler, ArmonAir RespiClick, Flovent Diskus, and Flovent HFA (Fluticasone propionate): There are no dosage adjustment provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, fluticasone is primarily eliminated in the liver and serum concentrations may be elevated in patients with hepatic impairment. Use with caution and closely monitor.

Use: Labeled Indications

Asthma:

ArmonAir Digihaler, ArmonAir RespiClick, and Arnuity Ellipta: Maintenance treatment of asthma as prophylactic therapy in patients ≥5 years of age (Arnuity Ellipta) or ≥12 years of age (ArmonAir Digihaler and ArmonAir RespiClick).

Flovent Diskus and Flovent HFA: Maintenance treatment of asthma as prophylactic therapy in patients ≥4 years of age.

Limitations of use: Not indicated for relief of acute bronchospasm.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

​Chronic obstructive pulmonary disease (stable)Level of Evidence [G]

Based on the Global Initiative for Chronic Obstructive Lung Disease guidelines for the management of chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICS) may be considered as part of dual or triple combination therapy (with a long acting beta agonist [LABA] or with a LABA and long-acting muscarinic antagonist), respectively, in patients with moderate to very severe COPD. However, regular treatment with ICS has been shown to increase the risk of pneumonia, especially in those with severe disease. Combination therapy is recommended in patients with a history of hospitalization(s) for exacerbations of COPD, ≥2 moderate exacerbations of COPD per year, blood eosinophils >300 cells/microliter, and concomitant or history of asthma. Combination therapy may also be considered in patients with 1 moderate exacerbation of COPD per year and blood eosinophils of 100 to 300 cells/microliter Ref.

​Eosinophilic esophagitis (oral)Level of Evidence [B, G]

Data from controlled trials and meta-analyses indicate that inhalational fluticasone propionate, when swallowed rather than inhaled, is effective at improving the clinicopathologic features of eosinophilic esophagitis Ref.

Guidelines from the American College of Gastroenterology and consensus recommendations from the American Gastroenterological Association (AGA) Institute/North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition on the management of eosinophilic esophagitis recommend oral administration of inhalational corticosteroids (eg, fluticasone, budesonide) as first-line therapy in adults and children with eosinophilic esophagitis and that the corticosteroid type and duration of therapy be individualized. They note that symptoms often recur upon discontinuation, and steroid resistance has been reported Ref. AGA Institute/Joint Task Force on Allergy-Immunology Practice Parameters guidelines also recommend oral administration of inhalational corticosteroids over oral glucocorticosteroid therapy or no treatment for patients with eosinophilic esophagitis Ref. Access Full Off-Label Monograph.

Level of Evidence Definitions

​Level of Evidence Scale

Class and Related Monographs

Corticosteroids

Clinical Practice Guidelines

Asthma:

Canadian Thoracic Society, “Asthma Management Continuum - 2010 Consensus Summary for Children Six Years of Age and over, and Adults,” January/February 2010

ERS/ATS, "Management of Severe Asthma," September 2019

GINA, "Global Strategy for Asthma Management and Prevention," 2020 Update

NHLBI and NAEPP The Expert Panel Report 3: “Guidelines for the Diagnosis and Management of Asthma,” Full Report 2007

Chronic Cough:

CHEST, "Managing Chronic Cough due to Asthma and NAEB in Adults and Adolescents," January 2020

COPD:

Canadian Thoracic Society Recommendations for Management of Chronic Obstructive Pulmonary Disease, 2007 Update

GOLD, “Global Strategy for Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease," 2019

Administration: Oral

Oral (off-label use/route): For the treatment of eosinophilic esophagitis (off-label use), fluticasone is administered orally with a metered-dose inhaler without the use of a spacer. Administer as a spray into the mouth and swallow (do not inhale). Patients should not rinse, eat, or drink for 30 to 60 minutes after administration (ACG [Dellon 2013]; Konikoff 2006; Richter 2016; Teitelbaum 2002).

Administration: Inhalation

Dry powder inhaler:

ArmonAir RespiClick: Administer the dose at approximately the same time every day. Does not require priming and do not use with a spacer or volume holding chamber. Following administration, rinse mouth with water after use (do not swallow). Do not wash or place any part of inhaler in water; if mouthpiece needs cleaning, gently wipe with a dry cloth or tissue. Discard inhaler 30 days after opening the foil pouch or when the counter reads "0", whichever comes first (device is not reusable).

ArmonAir Digihaler: Administer the dose at approximately the same time every day. Does not require priming and do not use with a spacer or volume holding chamber. Following administration, rinse mouth with water after use (do not swallow). Do not wash or place any part of inhaler in water; if mouthpiece needs cleaning, gently wipe with a dry cloth or tissue. Discard inhaler 30 days after opening the foil pouch or when the counter reads "0" (whichever comes first).

Arnuity Ellipta: Administer the dose at the same time every day. Do not shake inhaler. When ready to use, open and prepare mouthpiece of the inhaler and slide the cover down to activate the first dose. Exhale fully (not into mouthpiece), take one deep breath through mouth without blocking air vents and hold breath for about 3 to 4 seconds. If the cover is opened and closed without inhaling the medicine, the dose will be lost. The lost dose will be held in the inhaler, but it will no longer be available to be inhaled. It is not possible to accidentally take a double dose or an extra dose in one inhalation. Following administration, rinse mouth with water after use (do not swallow). Routine cleaning of the inhaler is not required; may clean the mouthpiece if needed, using a dry tissue, before the cover is closed. Discard inhaler 6 weeks after opening the foil tray or when the counter reads "0" (device is not reusable).

Flovent Diskus: Do not use with a spacer device. Do not exhale into Diskus. Do not wash or take apart. Use in horizontal position; do not tilt. Rinse mouth with water (without swallowing) after each use. Discard after 6 weeks (50 mcg diskus) or after 2 months (100 mcg and 250 mcg diskus) once removed from protective pouch or when the dose counter reads "0", whichever comes first (device is not reusable).

Metered dose inhaler: Flovent HFA: Shake container thoroughly for 5 seconds before each inhalation. Use inhaler on inspiration. Allow 30 seconds between inhalations. Rinse mouth with water (without swallowing) after each use. Inhaler must be primed before first use, when not used for 7 days, or if dropped. To prime the first time, release 4 sprays into air; shake well for 5 seconds before each spray and spray away from face. The counter should read "120". If dropped or not used for 7 days, prime by shaking well for 5 seconds and releasing a single test spray. Patient should contact pharmacy for refill when the dose counter reads "020". Discard device when the dose counter reads "000". Do not use "float" test to determine contents. Clean the inhaler at least once weekly; use a cotton swab dampened with water to clean circular opening of the metal canister and wipe the inside of the mouthpiece with a tissue dampened with water. The use of a spacer may be recommended in certain patient populations (eg, young children, elderly) (GINA 2020).

Administration: Pediatric

Oral inhalation: Rinse mouth with water (without swallowing) after inhalation to decrease chance of oral candidiasis.

Metered-dose inhaler: Flovent HFA (Fluticasone propionate): Shake canister well for 5 seconds before each spray. Inhaler must be primed before first use with 4 test sprays (spray into air away from face, shake well for 5 seconds between sprays) and primed again with 1 test spray if not used for >7 days or if dropped. Use a spacer device for children <5 years of age and consider adding a face mask for infants and children <4 years of age (GINA 2018). Patient should contact pharmacy for refill when the dose counter reads "020." Discard device when the dose counter reads "000." Do not try to alter numbers on counter or remove the counter from the metal canister. Do not immerse canister into water (ie, do not use "float test" to determine contents). Clean the inhaler at least once weekly; use a cotton swab dampened with water to clean circular opening of the metal canister and wipe the inside of the mouthpiece with a tissue dampened with water.

Dry powder inhaler:

ArmonAir Digihaler, ArmonAir RespiClick (Fluticasone propionate): Administer the dose at approximately the same time every day. Does not require priming and do not use with a spacer or volume holding chamber. Do not wash or place any part of inhaler in water; if mouthpiece needs cleaning, gently wipe with a dry cloth or tissue. Patient should contact pharmacy for refill when the dose counter reads "020." Discard inhaler 30 days after opening the foil pouch or when the counter reads "0," whichever comes first (device is not reusable).

Arnuity Ellipta (Fluticasone furoate): Administer the dose at the same time every day. Do not shake inhaler. When ready to use, open and prepare mouthpiece of the inhaler and slide the cover down to activate the first dose. Exhale fully (not into mouthpiece), take one deep breath through mouth without blocking air vents and hold breath for about 3 to 4 seconds. If the cover is opened and closed without inhaling the medicine, the dose will be lost. The lost dose will be held in the inhaler, but it will no longer be available to be inhaled. It is not possible to accidentally take a double dose or an extra dose in one inhalation. Routine cleaning of the inhaler is not required; may clean the mouthpiece if needed, using a dry tissue, before the cover is closed. Discard inhaler 6 weeks after opening the foil tray or when the counter reads "0," whichever comes first (device is not reusable).

Flovent Diskus (Fluticasone propionate): Do not use with spacer device. Do not exhale into Diskus. Do not wash or take apart. Activate and use Diskus in horizontal position; do not tilt. Discard after 6 weeks (50 mcg diskus) or after 2 months (100 mcg and 250 mcg diskus) once removed from protective pouch or when the dose counter reads “0,” whichever comes first (device is not reusable).

Oral (swallowed): Note: This method of administration is for treatment of eosinophilic esophagitis only. Use metered dose inhaler. Do not use a spacer. Shake canister well for 5 seconds before each spray. Prime inhaler as outlined above. Actuate inhaler and spray medication into pharynx; swallow the medication (rather than inhale). Do not eat, drink, or rinse mouth for 30 minutes following administration (Dellon 2013; Konikoff 2006; Schaefer 2008; Teitelbaum 2002).

Dietary Considerations

ArmonAir Digihaler, ArmonAir RespiClick, Arnuity Ellipta, and Flovent Diskus may contain lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Storage/Stability

Metered dose inhaler (fluticasone propionate [aerosol]): Store between 20°C and 25°C (68°F and 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Discard device when the dose counter reads "000." Store with mouthpiece down. Do not expose to temperatures greater than 48.8°C (120°F). Do not puncture or incinerate.

Dry powder inhaler (fluticasone furoate and fluticasone propionate [Diskus]): Store between 20°C and 25°C (68°F and 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Store in a dry place away from direct heat or sunlight. Discard after 6 weeks (50 mcg Diskus and Arnuity Ellipta), after 2 months (100 and 250 mcg Diskus), or after 30 days (ArmonAir RespiClick) from removal from protective foil pouch or when the dose counter reads "0" (whichever comes first); device is not reusable.

Dry powder inhaler (fluticasone propionate [ArmonAir Digihaler]): Store between 15°C and 25°C (59°F and 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Store in a dry place away from extreme heat, cold, or humidity. Discard after 30 days from removal from protective foil pouch or when the dose counter reads "0" (whichever comes first); device is not reusable.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat asthma.

• Do not use this drug to treat an asthma attack. Use a rescue inhaler. Talk with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Common cold symptoms

• Throat irritation

• Sore throat

• Flu-like signs

• Muscle pain

• Nausea

• Vomiting

• Diarrhea

• Nose irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss

• Cushing syndrome like weight gain in upper back or abdomen; moon face; severe headache; or slow healing

• Severe loss of strength and energy

• Irritability

• Tremors

• Fast heartbeat

• Confusion

• Dizziness

• Flushing

• Sweating a lot

• Thrush

• Bone pain

• Joint pain

• Vision changes

• Change in voice

• Trouble speaking

• Trouble breathing

• Wheezing

• Cough

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

​International issues:

Contraindications

Hypersensitivity to fluticasone or any component of the formulation; severe hypersensitivity to milk proteins or lactose (ArmonAir Digihaler, ArmonAir RespiClick, Arnuity Ellipta, Flovent Diskus); primary treatment of status asthmaticus or other acute episodes of asthma requiring intensive measures.

Documentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Flovent HFA and Flovent Diskus: Untreated fungal, bacterial, or tubercular infections of the respiratory tract.

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. 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 due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, infections (particularly gastroenteritis), or other conditions with severe electrolyte loss. Select surgical patients on long-term, high-dose, inhaled corticosteroids (ICS) should be given stress doses of hydrocortisone IV during the surgical period and the dose reduced rapidly within 24 hours after surgery (NAEPP 2007).

• 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 and institute alternative therapy.

• Hypersensitivity: Immediate hypersensitivity reactions (eg, angioedema, bronchospasm, hypotension, rash, urticaria), including anaphylaxis, may occur.

• 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 viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox and 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.

• Oral candidiasis: Local oropharyngeal Candida infections have been reported; if this occurs, treat appropriately while continuing therapy. Patients should be instructed to rinse mouth with water without swallowing after each use.

• Vasculitis: Rare cases of vasculitis (eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]) or other systemic eosinophilic conditions can occur; often associated with decrease and/or withdrawal of oral corticosteroid therapy following initiation of inhaled corticosteroid.

Disease-related concerns:

• Asthma: Appropriate use: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Use is contraindicated in status asthmaticus or during other acute episodes of asthma requiring intensive measures.

• Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral count 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.

• Hepatic impairment: Use with caution in patients with hepatic impairment. Impairment of liver function may lead to accumulation of fluticasone in plasma.

• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use. Consider routine eye exams in chronic users.

• Pneumonia: Inhaled corticosteroids, including fluticasone, have been associated with an increased risk of pneumonia in some long-term studies (>6 months) in COPD patients (Dransfield 2013; Yang 2012). In addition, an observational study found a reduction in this risk when the inhaled corticosteroid was discontinued, particularly so with fluticasone (Suissa 2015).

Special populations:

• Pediatric: Orally inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients (~1 centimeter per year [range: 0.3 to 1.8 cm per year] and related to dose and duration of exposure). To minimize the systemic effects of orally inhaled corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.

Dosage form specific issues:

• ArmonAir Digihaler, ArmonAir RespiClick, Arnuity Ellipta, and Flovent Diskus: May contain lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Other warnings/precautions:

• Discontinuation of therapy: A gradual tapering of dose may be required prior to discontinuing therapy; there have been reports of systemic corticosteroid withdrawal symptoms (eg, joint/muscle pain, lassitude, depression) when withdrawing oral inhalation therapy.

• Transfer to oral inhaler: When transferring to oral inhalation therapy from systemic corticosteroid therapy, previously suppressed allergic conditions (rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions) may be unmasked. Withdraw systemic corticosteroid therapy by gradually tapering the dose. Monitor lung function, beta-agonist use, asthma symptoms, and for signs and symptoms of adrenal insufficiency (eg, fatigue, lassitude, weakness, nausea/vomiting, hypotension) during withdrawal.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

No specific geriatric information is available. No differences in safety have been observed in the elderly when compared to younger patients. Based on current data, no dosage adjustment is needed based on age. Counsel on proper use of inhaler and evaluate the patient's or caregiver's ability to correctly administer this inhaled medication.

Warnings: Additional Pediatric Considerations

Although recommended in children ≥12 years and adolescents, using higher doses (quintupled) in children <12 years of age has not shown efficacy and may be associated with a higher risk of adverse effects. A study in children 5 to 11 years of age with mild to moderate persistent asthma evaluated quintupling the dose of the inhaled corticosteroid (fluticasone) following the early signs of decreased asthma control; results showed that quintupled fluticasone dosages did not reduce the rate of severe exacerbations and may have been associated adverse effects (decreased linear growth, particularly in patients <8 years of age) (Jackson 2018).

Pregnancy Considerations

Fluticasone can be detected in cord blood following maternal use via oral inhalation during pregnancy (Battista 2016).

Maternal use of inhaled corticosteroids (ICS) in usual doses is not associated with an increased risk of fetal malformations; a small risk of malformations was observed in one study following high maternal doses of an alternative ICS. Uncontrolled asthma is associated with adverse events in pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes) (ERS/TSANZ [Middleton 2020]; GINA 2020).

ICS are recommended for the treatment of asthma during pregnancy (GINA 2020). Fluticasone oral inhalation is considered compatible for use during pregnancy. Pregnant females adequately controlled on fluticasone for asthma may continue therapy; if initiating treatment during pregnancy, use of an agent with more data in pregnant females may be preferred. The lowest dose that maintains asthma control should be used. Maternal asthma symptoms should be monitored monthly during pregnancy (ERS/TSANZ [Middleton 2020]).

Data collection to monitor pregnancy and infant outcomes associated with asthma and the medications used to treat asthma in pregnancy is ongoing. Health care providers are encouraged to enroll exposed pregnant females in the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (877-311-8972 or https://mothertobaby.org). Patients may also enroll themselves.

Breast-Feeding Considerations

It is not known if sufficient quantities of fluticasone are absorbed following inhalation to produce detectable amounts in breast milk.

Systemic corticosteroids are present in human milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, females with asthma should be encouraged to breastfeed (GINA 2020). Fluticasone oral inhalation is considered compatible with breastfeeding (ERS/TSANZ [Middleton 2020]).

Briggs' Drugs in Pregnancy & Lactation

• Fluticasone

Adverse Reactions

>10%:

Central nervous system: Fatigue (≤16%), malaise (≤16%), headache (5% to 14%)

Gastrointestinal: Oral candidiasis (2% to 31%)

Neuromuscular & skeletal: Arthralgia (17%), musculoskeletal pain (3% to 12%)

Respiratory: Sinus infection (≤33%), sinusitis (≤33%), upper respiratory tract infection (6% to 31%), throat irritation (≤22%), nasal congestion (16%), rhinitis (3% to 13%)

1% to 10%:

Cardiovascular: Hypertension (<3%), subarachnoid hemorrhage (≤1%)

Central nervous system: Pain (10%), voice disorder (≤9%), dizziness (<3%)

Dermatologic: Skin rash (8%), pruritus (6%)

Gastrointestinal: Nausea and vomiting (8% to 9%), viral gastrointestinal infection (3% to 5%), gastrointestinal distress (≤4%), gastrointestinal pain (≤4%), oropharyngeal candidiasis (3%), toothache (3%), viral gastroenteritis (3%)

Hematologic & oncologic: Malignant neoplasm of breast (≤1%)

Infection: Viral infection (5%), influenza (<3%), abscess (≤1%)

Neuromuscular & skeletal: Muscle injury (2% to 5%), limb pain (<3%), muscle spasm (<3%), sprain (<3%)

Respiratory: Hoarseness (≤9%), cough (5% to 9%), viral respiratory tract infection (5% to 9%), nasopharyngitis (5% to 8%), bronchitis (2% to 8%), pharyngitis (4%), upper respiratory tract inflammation (2% to 5%), oropharyngeal pain (3%), epistaxis (<3%), respiratory tract infection (<3%)

Miscellaneous: Fever (≤7%), accidental injury (2% to 5%)

Frequency not defined:

Cardiovascular: Edema, palpitations

Central nervous system: Migraine, mood disorder, mouth pain

Dermatologic: Acne vulgaris, dermatitis, dermatologic disorders, eczema, folliculitis, photodermatitis, viral skin infection

Endocrine & metabolic: Cushingoid appearance, fluid volume disorder, weight gain

Gastrointestinal: Change in appetite, diarrhea, dyspepsia, gastrointestinal signs and symptoms, oral mucosal erythema, oral mucosa ulcer, oral rash, tongue disease

Genitourinary: Urinary tract infection

Hematologic & oncologic: Polyp (ENT)

Infection: Bacterial infection, bacterial reproductive infection, fungal infection

Ophthalmic: Blepharoconjunctivitis, conjunctivitis, keratitis

Respiratory: Allergic rhinitis, constriction of the pharynx, ENT signs and symptoms, laryngitis, rhinorrhea

Miscellaneous: Soft tissue injury, swelling

<1%, postmarketing, and/or case reports: Aggressive behavior, agitation, allergic skin reaction, anaphylaxis, angioedema, anxiety, aphonia, behavioral changes, blurred vision, bronchospasm, bruise, cataract, chest symptoms, chest tightness, decreased linear skeletal growth rate, dental caries, dental discomfort, depression, dyspnea, ecchymoses, esophageal candidiasis, exacerbation of asthma, facial edema, gastrointestinal disease, glaucoma, hyperactive behavior, hyperglycemia, hypersensitivity reaction, increased intraocular pressure, irritability, mouth disease, oropharyngeal edema, osteoporosis, paradoxical bronchospasm, pneumonia, restlessness, retinopathy (central serous), sore throat, staining of tooth, type IV hypersensitivity reaction, wheezing

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Corticosteroid Allergy

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

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

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

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

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

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

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

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Fluticasone (Oral Inhalation). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Fluticasone (Oral Inhalation). Risk D: Consider therapy modification

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

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

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

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

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

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

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

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk X: Avoid combination

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. Risk D: Consider therapy modification

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

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

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification

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

Genes of Interest

• Cytochrome P450 3A4

Monitoring Parameters

Growth (adolescents and children via stadiometry); signs/symptoms of HPA axis suppression/adrenal insufficiency; signs/symptoms of oral candidiasis; possible eosinophilic conditions (including Churg-Strauss syndrome); FEV1, peak flow, and/or other pulmonary function tests; asthma symptoms; bone mineral density; hepatic impairment; glaucoma/cataracts

Advanced Practitioners Physical Assessment/Monitoring

When changing from systemic steroids to inhalational steroids, taper reduction of systemic medication slowly (may take several months). Monitor growth with long-term use in pediatric patients. Assess for signs and symptoms of HPA axis suppression/adrenal insufficiency. Assess for ocular changes. Assess for signs and symptoms of oral Candida infection with long-term use. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Obtain peak flow, FEV 1 and other pulmonary function tests. Obtain hepatic function tests. Monitor for possible eosinophilic condicitons (including Churg Strauss syndrome).

Nursing Physical Assessment/Monitoring

Check lab and pulmonary function test results and report abnormalities. Instruct patient on proper administration.

Product Availability

ArmonAir RespiClick has been discontinued in the United States for >1 year.

Dosage Forms Considerations

Flovent HFA 10.6 g and 12 g canisters contain 120 inhalations.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Aerosol, Inhalation, as propionate:

Flovent HFA: 44 mcg/actuation (10.6 g); 110 mcg/actuation (12 g); 220 mcg/actuation (12 g)

Aerosol Powder Breath Activated, Inhalation, as furoate:

Arnuity Ellipta: 50 mcg/actuation (30 ea); 100 mcg/actuation (14 ea, 30 ea); 200 mcg/actuation (14 ea, 30 ea) [contains lactose monohydrate]

Aerosol Powder Breath Activated, Inhalation, as propionate:

ArmonAir Digihaler: 55 mcg/actuation (1 ea); 113 mcg/actuation (1 ea); 232 mcg/actuation (1 ea) [contains alpha-lactose monohydrate]

ArmonAir RespiClick 55: 55 mcg/actuation (1 ea [DSC]) [contains lactose monohydrate]

ArmonAir RespiClick 232: 232 mcg/actuation (1 ea [DSC]) [contains lactose monohydrate]

ArmonAir RespiClick 113: 113 mcg/actuation (1 ea [DSC]) [contains lactose monohydrate]

Flovent Diskus: 50 mcg/blister (60 ea); 100 mcg/blister (28 ea, 60 ea); 250 mcg/blister (28 ea, 60 ea) [contains lactose]

Dosage Forms: Canada

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

Aerosol, Inhalation, as propionate:

Flovent HFA: 50 mcg/actuation (6 g, 13 g); 125 mcg/actuation (7.5 g, 13 g); 250 mcg/actuation (7.5 g, 13 g)

Aerosol Powder Breath Activated, Inhalation:

Flovent Diskus: 500 mcg/blister (1 ea) [contains lactose, milk protein]

Aerosol Powder Breath Activated, Inhalation, as furoate:

Arnuity Ellipta: 100 mcg/actuation (14 ea, 30 ea); 200 mcg/actuation (14 ea, 30 ea) [contains lactose monohydrate]

Aerosol Powder Breath Activated, Inhalation, as propionate:

Aermony RespiClick: 55 mcg/actuation (1 ea); 232 mcg/actuation (1 ea); 113 mcg/actuation (1 ea) [contains lactose monohydrate]

Flovent Diskus: 100 mcg/blister (1 ea); 250 mcg/blister (1 ea) [contains lactose, milk protein]

Anatomic Therapeutic Chemical (ATC) Classification

• R03BA05

Generic Available (US)

No

Pricing: US

Aerosol (Flovent HFA Inhalation)

44 mcg/ACT (per gram): $21.83

110 mcg/ACT (per gram): $25.81

220 mcg/ACT (per gram): $40.09

Aerosol powder (ArmonAir Digihaler Inhalation)

55 mcg/ACT (per each): $286.80

113 mcg/ACT (per each): $286.80

232 mcg/ACT (per each): $358.80

Aerosol powder (Arnuity Ellipta Inhalation)

50 mcg/ACT (per each): $7.15

100 mcg/ACT (per each): $7.15

200 mcg/ACT (per each): $9.57

Aerosol powder (Flovent Diskus Inhalation)

50 mcg/blister (per each): $3.66

100 mcg/blister (per each): $4.81

250 mcg/blister (per each): $6.44

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Fluticasone belongs to a group of corticosteroids which utilizes a fluorocarbothioate ester linkage at the 17 carbon position; extremely potent vasoconstrictive and anti-inflammatory activity. The effectiveness of inhaled fluticasone is due to its direct local effect.

Pharmacodynamics/Kinetics

Onset of action: Maximal benefit may take 1 to 2 weeks or longer.

Absorption: Absorbed systemically primarily via lungs (Flovent Diskus: ~18%); minimal GI absorption (<1%) due to presystemic metabolism.

Distribution: 4.2 L/kg.

Protein binding: >99%.

Metabolism: Hepatic via CYP3A4 to 17β-carboxylic acid (negligible activity).

Bioavailability: Oral inhalation: 13.9%; Flovent Diskus: ~8%.

Half-life elimination: IV: ~8 hours; Oral inhalation: Fluticasone furoate: 24 hours (plasma elimination phase following repeat dosing); Fluticasone propionate: ~11.2 hours (terminal half-life).

Time to peak, plasma: 0.5 to 1 hour.

Excretion: Feces (as parent drug and metabolites); urine (<5% as metabolites).

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: Accumulation of fluticasone in plasma may occur.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Localized infections with Candida albicans or Aspergillus niger have occurred frequently in the mouth and pharynx with repetitive use of oral inhaler of corticosteroids. These infections may require treatment with appropriate antifungal therapy or discontinuance of treatment with corticosteroid inhaler.

Effects on Bleeding

No information available to require special precautions

Related Information

• Inhalant Agents

Pharmacotherapy Pearls

Effects of inhaled steroids on growth have been observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally-inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for “catch up” growth following discontinuation of treatment with inhaled corticosteroids has not been adequately studied.

In the United States, dosage for the metered dose inhaler (Flovent HFA) is expressed as the amount of drug which leaves the actuator and is delivered to the patient. This differs from other countries, which express the dosage as the amount of drug which leaves the valve.

Index Terms

ArmonAir RespiClick; Flovent; Fluticasone Furoate; Fluticasone Propionate

FDA Approval Date

March 27, 1996

References

Alexander JA, Jung KW, Arora AS, et al. Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2012;10(7):742-749.e1. doi:10.1016/j.cgh.2012.03.018[PubMed 22475741]

Andreae DA, Hanna MG, Magid MS, et al. Swallowed fluticasone propionate is an effective long-term maintenance therapy for children with eosinophilic esophagitis. Am J Gastroenterol. 2016;111(8):1187-1197.[PubMed 27325220]

ArmonAir Digihaler (fluticasone propionate inhalation powder) [prescribing information]. Parsippany, NJ: Teva Pharmaceuticals USA Inc; June 2020.

ArmonAir Respiclick (fluticasone propionate inhalation powder) [prescribing information]. Parsippany, NJ: Teva Pharmaceuticals USA, Inc; September 2020.

Arnuity Ellipta (fluticasone furoate inhalation powder) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; January 2019.

Arnuity Ellipta (fluticasone furoate inhalation powder) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; October 2018.

Battista MC, Boutin M, Venne P, et al. Maternal inhaled fluticasone propionate intake during pregnancy is detected in neonatal cord blood. Bioanalysis. 2016 Jun 28. [Epub ahead of print][PubMed 27349687]

Biggadike K. Fluticasone furoate/fluticasone propionate - different drugs with different properties. Clin Respir J. 2011;5(3):183-184. doi: 10.1111/j.1752-699X.2011.00244.x.[PubMed 21569222]

Butz BK, Wen T, Gleich GJ, Furuta GT, at al. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014;147(2):324-333.e5. doi:10.1053/j.gastro.2014.04.019[PubMed 24768678]

Chuang MY, Chinnaratha MA, Hancock DG, et al. Topical steroid therapy for the treatment of eosinophilic esophagitis (EoE): A systematic review and meta-analysis. Clin Transl Gastroenterol. 2015;6:e82. doi:10.1038/ctg.2015.9[PubMed 25809314]

Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA; American College of Gastroenterology. ACG clinical guideline: evidence based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013;108(5):679-692. doi:10.1038/ajg.2013.71[PubMed 23567357]

Dransfield MT, Bourbeau J, Jones PW, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials [published correction appears in Lancet Respir Med. 2013;1(3):186]. Lancet Respir Med. 2013;1(3):210-223. doi: 10.1016/S2213-2600(13)70040-7.[PubMed 24429127]

Dugas MA, Nguyen D, Frenette L, et al, "Fluticasone Inhalation in Moderate Cases of Bronchopulmonary Dysplasia," Pediatrics, 2005, 115(5):566-72.[PubMed 15833887]

Flovent Diskus (fluticasone propionate inhalation powder) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; July 2020.

Flovent Diskus (fluticasone propionate inhalation powder) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; August 2020.

Flovent HFA (fluticasone propionate inhalation aerosol) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; January 2019.

Flovent HFA (fluticasone propionate inhalation aerosol) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; August 2020.

Furuta GT, Katzka DA. Eosinophilic esophagitis. N Engl J Med. 2015;373(17):1640-1648. doi:10.1056/NEJMra1502863[PubMed 26488694]

Furuta GT, Liacouras CA, Collins MH, et al; First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-1363. doi:10.1053/j.gastro.2007.08.017[PubMed 17919504]

Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. http://www.ginasthma.org. Updated 2018. Accessed October 23, 2018.

Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf. Updated 2019. Accessed December 13, 2019.

Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf. Updated 2020. Accessed May 6, 2020.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2014 Report. Global Initiative for Chronic Obstructive Lung Disease website. Published 2014.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2019 Report. Global Initiative for Chronic Obstructive Lung Disease website. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Published 2019. Accessed July 25, 2019.

Goedert JJ, Vitale F, Lauria C, et al, “Risk Factors for Classical Kaposi's Sarcoma,” J Natl Cancer Inst, 2002, 94(22):1712-8.[PubMed 12441327]

Hirano I, Chan ES, Rank MA, et al; AGA Institute Clinical Guidelines Committee; Joint Task Force on Allergy-Immunology Practice Parameters. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters clinical guidelines for the management of eosinophilic esophagitis. Gastroenterology. 2020;158(6):1776‐1786. doi:10.1053/j.gastro.2020.02.038[PubMed 32359562]

Hirano I, Furuta GT. Approaches and challenges to management of pediatric and adult patients with eosinophilic esophagitis. Gastroenterology. 2020;158(4):840-851. doi:10.1053/j.gastro.2019.09.052[PubMed 31836530]

Jackson DJ, Bacharier LB, Mauger DT, et al. Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. N Engl J Med. 2018;378(10):891-901.[PubMed 29504498]

Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131(5):1381-1391. doi:10.1053/j.gastro.2006.08.033[PubMed 17101314]

Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011;128(1):3-20.e6. doi:10.1016/j.jaci.2011.02.040[PubMed 21477849]

Lougheed MD, Lemière C, Dell SD, et al, “Canadian Thoracic Society Asthma Management Continuum - 2010 Consensus Summary for Children Six Years of Age and Over, and Adults,” Can Respir J, 2010, 17(1):15-24.[PubMed 20186367]

McKeever T, Mortimer K, Wilson A, et al. Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations. N Engl J Med. 2018;378(10):902-910. doi: 10.1056/NEJMoa1714257.[PubMed 29504499]

Middleton PG, Gade EJ, Aguilera C, et al. ERS/TSANZ Task Force Statement on the management of reproduction and pregnancy in women with airways diseases. Eur Respir J. 2020;55(2):1901208. doi:10.1183/13993003.01208-2019[PubMed 31699837]

Moawad FJ, Veerappan GR, Dias JA, Baker TP, Maydonovitch CL, Wong RK. Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia. Am J Gastroenterol. 2013;108(3):366-372. doi:10.1038/ajg.2012.443[PubMed 23399553]

Murali AR, Gupta A, Attar BM, Ravi V, Koduru P. Topical steroids in eosinophilic esophagitis: systematic review and meta-analysis of placebo controlled randomized clinical trials. J Gastroenterol Hepatol. 2016;31(6):1111-1119. doi:10.1111/jgh.13281[PubMed 26699695]

National Asthma Education and Prevention Program (NAEPP), Expert Panel Report 3, "Guidelines for the Diagnosis and Management of Asthma," Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 08-4051, prepublication 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm

Peterson KA, Thomas KL, Hilden K, Emerson LL, Wills JC, Fang JC. Comparison of esomeprazole to aerosolized, swallowed fluticasone for eosinophilic esophagitis. Dig Dis Sci. 2010;55(5):1313-1319. doi:10.1007/s10620-009-0859-4[PubMed 19533356]

Richter JE. Current management of eosinophilic esophagitis 2015. J Clin Gastroenterol. 2016;50(2):99-110. doi:10.1097/MCG.0000000000000430[PubMed 26485101]

Schaefer ET, Fitzgerald JF, Molleston JP, et al, "Comparison of Oral Prednisone and Topical Fluticasone in the Treatment of Eosinophilic Esophagitis: A Randomized Trial in Children," Clin Gastroenterol Hepatol, 2008, 6(2):165-73.[PubMed 18237866]

Suissa S, Coulombe J, Ernst P. Discontinuation of inhaled corticosteroids in COPD and the risk reduction of pneumonia. Chest. 2015;148(5):1177-1183. doi: 10.1378/chest.15-0627.[PubMed 26110239]

Teitelbaum JE, Fox VL, Twarog FJ, et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology. 2002;122(5):1216-1225.[PubMed 11984507]

Todd GR, Acerini CL, Buck JJ, et al, "Acute Adrenal Crisis in Asthmatics Treated With High-Dose Fluticasone Propionate," Eur Respir J, 2002, 19(6):1207-9.[PubMed 12108877]

Todd GR, Acerini CL, Ross-Russell R, et al, "Survey of Adrenal Crisis Associated With Inhaled Corticosteroids in the United Kingdom," Arch Dis Child, 2002, 87(6):457-61.[PubMed 12456538]

Valotis A, Högger P. Human receptor kinetics and lung tissue retention of the enhanced-affinity glucocorticoid fluticasone furoate. Respir Res. 2007;8:54.[PubMed 17650349]

Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;(7):CD002991. doi: 10.1002/14651858.CD002991.pub3.[PubMed 22786484]

Brand Names: International

Allegro (IL); Allevisone (TW); Arnuity (JP); Arnuity Ellipta (SG); Atemur Mite (DE); Axotide (CH); Dalman AQ (HK); Flixotaide (PT); Flixotide (AE, AR, AT, BE, BG, BH, BR, CL, CN, CY, CZ, DK, EC, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IL, IQ, IR, IS, IT, JM, JO, KR, KW, LB, LT, LU, LV, LY, MT, MX, MY, NL, NZ, OM, PE, PH, PK, PY, QA, RO, RU, SA, SE, SG, SI, SK, SY, TH, TR, TT, TW, UA, UY, VE, VN, YE, ZW); Flixotide Inhaler (AU); Flixotide Nebules (AU); Flixovate (FR); Flohale (AE, ZW); Flomist (MY); Flutaide (PT); Flutica (DE); Flutico (BD); Flutide (DE, SE); Flutimar HFA (CO); Flutitrim (SG); Flutivate (BR, DE); Futisone (TW); Medicort (ID); Meseca (VN); Nasofan (HK); Rheoran F (LK); Zoflut (IN)

Last Updated 10/20/20