Fluticasone (Oral Inhalation)

Dosage Forms

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 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]

Pharmacology

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.

Pharmacokinetics/Pharmacodynamics

Absorption

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

Distribution

4.2 L/kg

Metabolism

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

Excretion

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

Onset of Action

Maximal benefit may take 1 to 2 weeks or longer

Time to Peak

0.5 to 1 hour

Half-Life Elimination

IV: ~8 hours; Oral inhalation (plasma elimination phase following repeat dosing): 24 hours (ArmonAir RespiClick: ~11.2 hours)

Protein Binding

>99%

Use in Specific Populations

Special Populations: Hepatic Function Impairment

Accumulation of fluticasone in plasma may occur.

Use: Labeled Indications

Asthma:

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

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

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

Guideline recommendations: A low-dose inhaled corticosteroid (in addition to an as-needed short acting beta₂-agonist) is the initial preferred long-term control medication for children, adolescents, and adult patients with persistent asthma who are candidates for treatment according to a step-wise treatment approach (GINA 2018; NAEPP 2007).

Use: Off Label

Chronic obstructive pulmonary disease (stable)yes

Based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 update to the guidelines for the management of chronic obstructive pulmonary disease (COPD), long-term monotherapy with inhaled corticosteroids is not recommended. Regular treatment with ICS has been shown to increase the risk of pneumonia, especially in those with severe disease. Per the 2018 GOLD guideline update, combining two long acting bronchodilators (ie, long acting beta agonist [LABA] and long acting antimuscarinic [LAMA]) is more effective in reducing exacerbations than monotherapy or the combination of inhaled corticosteroid (ICS) and LABA. If symptoms are inadequately controlled on a bronchodilator regimen, addition of an ICS may be considered. Triple inhaled therapy of ICS/LAMA/LABA has been shown to improve lung function, symptoms, and health status and reduces exacerbations compared to ICS/LABA or LAMA monotherapy GOLD 2018.

Eosinophilic esophagitisbyes

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.

Guidelines from the American College of Gastroenterology (ACG) and consensus recommendations from the American Gastroenterological Association (AGA) regarding diagnosis and management of eosinophilic esophagitis recommend that oral administration of inhalational corticosteroids (eg, fluticasone, budesonide) be considered as first-line therapy in adults with eosinophilic esophagitis and that the corticosteroid type and duration of therapy be individualized. Symptoms often recur upon discontinuation, and steroid resistance has been reported. .

Contraindications

Hypersensitivity to fluticasone or any component of the formulation; severe hypersensitivity to milk proteins or lactose (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.

Dosage and Administration

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 (Fanta 2019; GINA 2018; McKeever 2018).

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 mcg 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 2018): 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:

National Asthma Education and Prevention Program guidelines (NAEPP 2007): Fluticasone propionate (HFA): Metered-dose inhaler:

Low-dose therapy: 88 to 264 mcg/day in divided doses twice daily.

Medium-dose therapy: >264 to 440 mcg/day in divided doses twice daily.

High-dose therapy: >440 mcg/day in divided doses twice daily.

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

Low-dose therapy: 100 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:

National Asthma Education and Prevention Program guidelines (NAEPP 2007): Fluticasone propionate: Dry powder inhaler:

Low-dose therapy: 100 to 300 mcg/day in divided doses twice daily.

Medium-dose therapy: >300 to 500 mcg/day in divided doses twice daily.

High-dose therapy: >500 mcg/day in divided doses twice daily.

Global Initiative for Asthma guidelines (GINA 2018): Fluticasone propionate: Dry powder 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 in combination with a long-acting bronchodilator (GOLD 2014; GOLD 2018).

Eosinophilic esophagitis (off-label use): Oral (off-label route): 440 to 880 mcg of aerosolized fluticasone swallowed (not inhaled) twice daily (880 to 1,760 mcg/day) (Alexander 2012; Butz 2014; Chuang 2015; Murali 2015).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: ArmonAir RespiClick discontinued in the US for >1 year.

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 RespiClick (fluticasone propionate): Dry powder inhaler: Children ≥12 years and Adolescents: Oral inhalation: Dosing based on previous asthma therapy:

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: Oral (swallowed): Note: Patients use an oral inhaler without a spacer and swallow the medication. Optimal dose and dosing regimen are not established:

General dosing range: Children and Adolescents: 88 to 440 mcg twice to four times daily; maximum daily dose: 1,760 mcg/day (Konikoff 2006; Liacouras 2011; Schaefer 2008; Teitelbaum 2002). Doses as high as 880 mcg twice daily have been reported (Butz 2014).

Age-based dosing:

Twice daily dosing (Teitelbaum 2002):

Children 2 to 4 years: 88 mcg twice daily.

Children 5 to 10 years: 220 mcg twice daily.

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

Four times daily dosing (Schaefer 2008):

Children ≤10 years: 220 mcg 4 times daily for 4 weeks, 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: 440 mcg 4 times daily for 4 weeks, 440 mcg 3 times daily for 3 weeks, 440 mcg twice daily for 3 weeks, 440 mcg daily for 2 weeks.

Administration

Oral 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).

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 now 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 2018).

Oral (off-label 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 may not rinse, eat, or drink for 30 minutes after administration (Dellon 2013; Konikoff 2006; Teitelbaum 2002).

Dietary Considerations

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

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.

Drug Interactions

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adverse Reactions

>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

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: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Short-acting beta₂-agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments. 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).

Concurrent drug therapy issues:

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

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 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.

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

Pregnancy

Pregnancy Considerations

Fluticasone can be detected in cord blood following maternal use via oral inhalation during pregnancy (Battista 2016). Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications (ACOG 2008; GINA 2018).

Inhaled corticosteroids are recommended for the treatment of asthma during pregnancy (ACOG 2008; GINA 2018; Namazy 2016). 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 (Namazy 2016).

Patient Education

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.

Frequently reported side effects of this drug

• Headache
• Sore throat
• Flu-like signs
• Muscle pain
• Nausea
• Vomiting
• Diarrhea
• Runny nose
• Stuffy nose

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• 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 a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.