FLONASE ALLERGY RELIEF (Brand for FLUTICASONE PROPIONATE)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
Oral inhalation aerosol (Flovent HFA)*
NOTE: Use of the oral inhalation aerosol for swallowed topical administration is not approved by the FDA.
-Puff the inhaler into the mouth during a breath hold, and then swallow.
-Avoid eating or drinking for 30 to 60 minutes after dosing.


Topical Administration
-For topical dermatologic use only. Not for ophthalmic, oral, or intravaginal use. Avoid contact with eyes.
-Patients who fail to respond to topical fluticasone treatment after 2 weeks should be re-evaluated.
-Once control of the treated condition has been achieved, discontinue fluticasone treatment. Intermittent application may be needed to maintain remission or control of the condition in some cases. The lowest effective maintenance application should be used. Other options include changing to a less potent topical corticosteroid for maintenance and control of inflammation and symptoms.
-Fluticasone propionate preparations generally should not be used with occlusive dressings, including diapers and plastic pants. Instruct patients and caregivers not to bandage, cover, or wrap area in any way that may be occlusive unless recommended by their physician.
Cream/Ointment/Lotion Formulations
-Wash hands before and after fluticasone application. Use gloves if required by universal precautions.
-Apply sparingly in a thin film and rub gently into affected area. Restrict application to the active lesions or affected areas and try to avoid normal surrounding skin.



Inhalation Administration
Oral Inhalation Administration
Oral inhalation aerosol (Flovent HFA):
-NOTE: The metered-dose inhalers deliver either 44 mcg/spray, 110 mcg/spray, or 220 mcg/spray depending on the formulation selected.
-Shake well before each use.
-Instruct the patient on proper inhalation technique. See the inhaler's "Instructions for Use".
-Flovent HFA should be primed prior to the initial use by releasing 4 sprays into the air, away from the face and other people. Shake well before each use. The inhaler should also be primed by releasing 1 spray into the air if it has not been used for 7 days or longer or if it is dropped.
-For patients unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) may be beneficial.
-The choice of using a mouthpiece versus a face mask with a spacer/VHC device must be made based on the skills and understanding of each individual patient.-In general, children less than 4 years of age require administration with a tight-fitting face mask and spacer/VHC device to achieve optimal delivery. If a face mask is used, allow 3 to 5 inhalations per actuation. Administration of fluticasone HFA via the AeroChamber Plus VHC with face mask has been shown to result in higher systemic exposure in patients ages 6 months to 3 years compared to children 4 to 11 years of age who receive the same dose without the VHC or face mask.

-Have the patient rinse the mouth thoroughly with water after administration to remove fluticasone deposited in the mouth; they should not swallow the water.
-The inhaler must be cleaned at least 1 time each week. Remove the canister and cap from the inhaler. Rinse the inhaler with warm water and let it air-dry overnight.
-To avoid the spread of infection, do not use the inhaler for more than 1 person.
-The canister contains a dose counter. The inhaler should be discarded after the counter reads "000". Although the canister is still operational and may contain medication, the accuracy of medication delivery cannot be assured. The patient should contact the pharmacist or provider regarding a refill when the counter reads "020".

Powder for oral inhalation (Flovent Diskus):
-Prior to initial use, instruct the patient to remove the Diskus device from the moisture-protective foil pouch and to safely throw away the foil pouch. The Diskus device will be in the closed position. The patient should fill in the "Pouch opened" and "Use by" dates in the blank lines on the label. The "Use by" date for Flovent Diskus 50 mcg is 6 weeks from the date the pouch is opened. The "Use by" date for Flovent Diskus 100 mcg and 250 mcg devices is 2 months from the date the pouch is opened.
-Instruct the patient on proper inhalation technique. See the inhaler's "Instructions for Use".
-Open the Diskus device by holding the device in one hand and using the thumb of the other hand to push the thumb grip away as far as it will go until the mouthpiece shows and snaps into place.
-Instruct the patient to hold the Diskus device in a level, flat position with the mouthpiece towards them and to slide the lever away from them as far as it will go until it clicks. The number on the dose counter will count down by 1; the Diskus device is now ready to use.
-To avoid releasing a dose by mistake before the patient is ready to inhale, warn the patient not to close or tilt the Diskus device, not to play with the lever, and not to slide the lever more than once.
-Before inhaling the dose, have the patient breathe out as far as they can while holding the Diskus device level and away from their mouth. They should never breathe out into the mouthpiece.
-Have the patient put the mouthpiece to their lips and breathe in through the mouth quickly and deeply through the Diskus device. Remove the Diskus device from the mouth, hold the breath for about 10 seconds, or for as long as it is comfortable, and then breathe out slowly.
-After taking a dose, the patient should close the Diskus device by sliding the thumb grip it back towards them far as it will go. The Diskus device will click shut. The lever will automatically return to its original position.
-Have the patient rinse the mouth thoroughly with water after administration to remove fluticasone deposited in the mouth; they should not swallow the water.
-To avoid the spread of infection, do not use the inhaler for more than 1 person.
-The counter displays how many doses are left. The counter number will count down each time the patient uses the Diskus device. After 55 doses (23 doses from the sample pack), the patient will see numbers "5" to "0" in red to warn that there are only a few doses left.

Powder for oral inhalation (Arnuity Ellipta):
-Administer via oral inhalation.
-Instruct the patient on proper inhalation technique. See the inhaler's "Instructions for Use".
-Instruct the patient to open and prepare the mouthpiece of the fluticasone inhaler and slide the cover down to activate the first dose. The counter counts down by 1 each time the patient opens the cover.
-Holding the inhaler mouthpiece level to, but away from, the mouth, the patient should exhale. Then, put the mouthpiece to the lips and have the patient breathe in the dose deeply and slowly. Remove the inhaler from the mouth, hold the breath for about 3 to 4 seconds, and then exhale slowly. Close the inhaler.
-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.
-Have the patient rinse the mouth thoroughly with water after administration to remove fluticasone deposited in the mouth; they should not swallow the water.
-Routine cleaning of the inhaler is not required; the patient can clean the mouthpiece if needed, using a dry tissue, before the cover is closed.
-To avoid the spread of infection, do not use the inhaler for more than 1 person.
-Discard inhaler after 30 sprays or when the counter reads "0", or when the expiration date has passed.

Powder for Oral Inhalation (Armonair Digihaler):
-Each canister is supplied with a white inhaler with the mouthpiece and a green cap that covers the mouthpiece.
-Instruct the patient on proper inhalation technique. See the inhaler's "Instructions for Use".
-Do not use the DPI with a spacer or valve holding chamber (VHC) device.
-Priming is not necessary.
-Instruct the patient to hold the inhaler upright and open the green cap all the way back until it "clicks" immediately prior to use. The inhaler does not need to be shaken. If a "click" is not heard then the inhaler may not be activated to give the dose of medicine.
-Before inhaling the dose, have the patient breathe out as far as they can while holding the DPI device level and away from their mouth. They should never breathe out into the DPI mouthpiece.
-Instruct the patient to put the mouthpiece to their lips and breathe in through the mouth quickly and deeply through the DPI device without blocking the vent above the mouthpiece. Remove the DPI device from the mouth, hold the breath for about 10 seconds, and then breathe out slowly.
-After taking a dose, close the cap; the cap should not be opened until the patient is ready for the next dose.
-The canister contains a dose counter. The inhaler contains 60 doses (inhalations) and will change to red when 20 doses are left. Patients should be instructed to request a refill when the counter reads 20. The inhaler should be discarded after the counter reads "0".
-Armonair Digihaler contains a built-in electronic module that detects, records, and stores data on inhaler events, including peak inspiratory flow rate. A mobile app is required for data transmission but is not required for the administration of fluticasone to the patient.
-Have the patient rinse the mouth thoroughly with water after administration to remove fluticasone deposited in the mouth; they should not swallow the water.
-To avoid the spread of infection, do not use the inhaler for more than 1 person.
-Safely dispose of the device by the specified "use by" date or when the counter reads "0", whichever comes first.

Intranasal Inhalation Administration
-For nasal use only.
-Instruct patient or caregiver on the proper use of the nasal spray.
-Shake well before each use.
-Do not use the bottle for more than the specified number of labeled doses.
-To avoid the spread of infection, do not use the sprayer for more than 1 person.

Fluticasone Propionate (e.g., Flonase products)
-Before first use, shake the bottle gently and pump the activator 6 times into the air, away from the face and other people until a fine wide spray appears. The unit should be re-primed if it has not been used for 7 days or more.
-The patient should blow their nose, close one nostril, and tilt head slightly forward. After placing the applicator into the open nostril, press down firmly and quickly on the applicator while breathing in. Expiration should occur through the mouth. Repeat for the other nostril.
-After administration, wipe the nasal applicator with a clean tissue and replace the cap. The nasal applicator should be cleaned at least 1 time each week. To clean, rinse the applicator with warm tap water, taking care not to suck water into the bottle, and allow to dry at room temperature before replacing the cap.

Fluticasone Furoate (e.g., Veramyst or Flonase Sensimist)
-Before first use, pump the activator 6 times into the air, away from the face and other people. If the cap has been left off the bottle for at least 5 days or spray has not been used for more than 30 days, re-prime by pumping the activator until a fine mist appears.
-The patient should blow their nose and tilt head slightly forward. After placing the applicator into the nostril with the nozzle pointed toward the outside of the nostril, press down on the applicator while breathing in. Expiration should occur through the mouth. Repeat for the other nostril.
-After administration, wipe the nozzle with a clean, try tissue. Do not use water to clean the nozzle. Clean the inside of the cap with a clean, dry tissue once weekly.

Fluticasone can cause hypothalamic-pituitary-adrenal (HPA) suppression. Manifestations of Cushing's syndrome and HPA suppression with possible adrenocortical insufficiency and withdrawal symptoms after treatment discontinuation can occur if topical fluticasone is applied over a large surface area, under occlusive dressings, or for prolonged periods of time. In such circumstances, periodic evaluation for HPA suppression is warranted. Pediatric patients may be more susceptible to systemic toxicity due to their larger skin surface to body mass ratio. HPA axis suppression occurred in 2 of 43 patients (4.7%) ages 3 months to 5 years who were treated for 3 to 4 weeks with fluticasone propionate cream 0.05%, covering a mean body surface area of 64% (range, 35 to 95%). Symptoms of hypercorticism may occur with fluticasone nasal spray or oral inhalation if recommended doses are exceeded or if patients are particularly sensitive to the effects of fluticasone. Two separate placebo-controlled studies in children 2 to 11 years old showed significantly decreased 24-hour urinary cortisol excretion in patients treated with normal doses of fluticasone furoate nasal spray. In a 6-week study, an assessment of serum cortisol concentrations demonstrated a mean change from baseline of -0.34 mcg/dL with a difference from placebo of -0.11 mcg/dL (95% CI: -0.88, 0.66). Cushingoid features have been observed during clinical practice with the use of fluticasone propionate oral inhalation. In addition, data from a prospective study of asthmatic children and adolescents (n = 143) on orally inhaled corticosteroids reported HPA suppression in 65.1% of patients. Concomitant intranasal corticosteroid use and a forced expiratory volume (FEV1)/forced vital capacity (FVC) less than 80% were linked to an increased incidence of adrenal suppression. If HPA suppression is noted, attempts to withdraw the drug or transition to a less potent steroid should be made. Signs and symptoms of glucocorticoid insufficiency may require systemic corticosteroids; patients with HPA suppression will require increased doses of corticosteroid therapy during periods of excessive stress.

Orally inhaled or intranasal corticosteroids may cause growth inhibition in pediatric patients; linear growth retardation has also been reported in pediatric patients after prolonged use of topical corticosteroids. Although data suggest that the effects on growth are minimal, the lowest effective dose of any corticosteroid dosage form should be utilized. In general, the benefits of regular inhaled corticosteroid (ICS) use outweigh the potential risk of relatively small and non-cumulative growth suppression in children with asthma; however, growth should be monitored. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients. Controlled clinical studies have shown that ICS may cause a mean reduction in growth velocity of approximately 1 centimeter (cm) per year (range: 0.3 to 1.8 cm/year) and that this reduction appears to depend on dose and duration of exposure. While not specifically addressing fluticasone, the Childhood Asthma Management Program (CAMP) trial suggested that ICS use to control asthma in children may affect final adult height (median follow-up 7 years) by approximately 1 cm. Meta-analysis suggests regular use of low or medium daily dose ICS is associated with a mean reduction of 0.48 cm per year in linear growth velocity (14 trials, n = 5,717; 95% CI -0.65 to -0.3, p less than 0.0001) and a 0.61 cm change from baseline in height (15 trials, n = 3,275; 95% CI -0.83 to -0.38, p less than 0.00001) in children with mild to moderate asthma during a 1-year treatment period. Specifically, fluticasone 100 to 200 mcg/day caused a mean reduction in growth velocity of 0.39 cm per year (5 trials, n = 1,405; 95% CI -0.63 to -0.15). This effect appears to be less pronounced after the first year of therapy and is not cumulative. In addition, a mean difference of -0.2 cm (n = 728; 95% CI 0.02 to 0.39) in growth velocity within the first year has been observed between low (50 to 100 mcg/day beclomethasone equivalent; 5.94 cm/year) and medium (200 mcg/day beclomethasone equivalent; 5.74 cm/year) dose ICS, indicating lower growth velocity in the those treated with higher dose ICS. Intranasal corticosteroids may also affect growth. Children (age range: 3 to 9 years) receiving 200 mcg/day of fluticasone propionate nasal spray were found to have a point estimate for growth velocity of 0.14 cm/year lower than children receiving placebo (95% CI ranging from 0.54 cm/year lower than placebo to 0.27 cm/year higher than placebo). Additionally, data from a 1-year placebo-controlled clinical growth study in children (age range: 5 to 8.5 years) receiving fluticasone furoate nasal spray 110 mcg/day showed a lower mean growth velocity compared with placebo (mean treatment difference -0.27 cm/year [95% CI -0.48 to -0.06]).

In clinical trials, the most frequently reported GI adverse events included abdominal pain (4% or less), diarrhea (1% to 3%), dyspepsia, nausea (1% to 9%), and vomiting (1% to 9%). Other adverse reactions affecting the GI tract included xerostomia and ageusia or loss of taste (intranasal). Hyposalivation, dental pain (3% or less), oral ulceration, dental caries, tooth decay, and tooth discoloration have been reported with orally inhaled fluticasone. Upper abdominal pain and diarrhea were reported in 3% or more of patients receiving a combination of orally inhaled fluticasone furoate and a long-acting beta-agonist during clinical trials. Although GI adverse events are much less likely to occur with topical fluticasone use, diarrhea and vomiting were both reported by 1% patients who received fluticasone lotion in clinical trials. Elevated hepatic enzymes (AST and ALT) were reported in 1 patient (4-month-old child) who received fluticasone lotion in clinical trials.

Children are more prone to systemic adverse effects of topical fluticasone because of larger skin surface to body weight ratio and thinner skin. Increased intracranial pressure has been reported in children receiving topical corticosteroids; manifestations of increased intracranial pressure include bulging fontanelles, headaches, and bilateral papilledema. Patients should avoid excessive administration of topical fluticasone. Additionally, there have been case reports of intracranial hypertension with both intranasal and inhaled fluticasone. Although this adverse effect is uncommon, caution is advised for all dosage forms, particularly in at risk populations.

Secondary bacterial, viral, and fungal infections (e.g., influenza (2% to 7%), oropharyngeal candidiasis (2% to 31%), esophageal candidiasis, otitis media (1% to 4%), pneumonia, viral gastroenteritis (3% to 5%), upper respiratory tract infection (14% to 20%), respiratory tract infection (1% to 5%), and urinary tract infection have been observed during treatment with inhaled fluticasone in both pediatric and adult patients. Local immunosuppression associated with inhaled fluticasone use may be manifested as an overgrowth of fungus in the nose, mouth, and throat; oral candidiasis (thrush) is a well-known adverse reaction of oral inhalation steroid therapy. The incidence may be correlated with daily dose and appears to occur less frequently in children. Using an add-on spacer device, reducing the frequency of use, and rinsing the mouth after use may minimize the incidence of oropharyngeal thrush. Localized Candida albicans infections were also reported during clinical trials with intranasal and topical fluticasone; the manufacturer recommends performing periodic evaluations for the presence of Candida infections. Infections may require discontinuation of fluticasone and treatment with appropriate local therapy. Additionally, health care providers are advised to be aware that use of corticosteroids may mask the manifestations of an infection.

Inhaled fluticasone, and rarely intranasal fluticasone, has been associated with the development of cataracts, increased intraocular pressure or ocular hypertension, and glaucoma in adults; the risk in pediatric patients is unclear. In adults, the risk increases with long-term and high-dose inhaled corticosteroid use. Other ocular adverse reactions associated with inhaled fluticasone therapy include blurred vision, blepharoconjunctivitis, conjunctivitis, ocular irritation, central serous chorioretinopathy, and xerophthalmia. The penetration of topical corticosteroids is more than 300 times greater through the eyelid than on other body sites. The use of topical corticosteroids around the eye has been associated with the development of glaucoma and visual loss when used for extended periods. Cataracts and glaucoma have been reported in adults during postmarketing experience with the use of topical corticosteroids. Evaluate any patient who develops changes in vision during topical corticosteroid therapy for ocular hypertension. Consider referral to an ophthalmologist in patients who develop ocular symptoms or who use inhaled or intranasal fluticasone long term.

Topical preparations of fluticasone may be associated with local adverse effects including urticaria (2%), telangiectasia (2% to 5%), erythematous rash (2%), erythema (1% to 2%), burning (1% to 2%), stinging (1% to 5%), skin infection (0.5%), impetigo (0.5%), atopic dermatitis (0.5%), eczema (0.5%), exacerbation of eczema (1.9%), infected eczema (0.5% to 1%), viral warts (0.5%), herpes simplex (0.5%), skin irritation (1% to 3%), pruritus (1% to 2%), exacerbation of pruritus (0.5% to 2%), folliculitis (0.5%), blisters (0.5%), excoriation (2%), and xerosis (0.5% to 7%). The following reactions have been infrequently reported with topical corticosteroid use: pustules, acneiform rash, skin hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, hypertrichosis, and miliaria; these reactions may occur more frequently with the use of occlusive dressings or higher potency corticosteroids. After reduction or discontinuation of topical therapy, there have been reports of pustular psoriasis from chronic plaque psoriasis. Dermatologic adverse events have also occurred after treatment with inhaled and nasal fluticasone. During clinical trials, persons receiving fluticasone have reported symptoms such as pruritis (6%), rash (unspecified)(8%), allergic dermatitis, contusion, hematoma, vesicular rash, photodermatitis, dermatosis, eczema, acne vulgaris, ecchymosis or purpura, folliculitis, and urticaria (nasal only). For patients receiving fluticasone oral inhalation with the assistance of a face mask, it is important to wash the face after treatment to limit local adverse effects.

In general, excessive use of corticosteroids can lead to impaired wound healing. Fluticasone should not be applied directly or near healing wounds. A propensity for skin ulcer may develop in patients with markedly impaired circulation who use topical corticosteroids.

Prolonged use (e.g., more than 1 year) of high doses of inhaled corticosteroids, such as fluticasone, especially when used in combination with frequent courses of systemic corticosteroids, may be associated with skeletal changes including reduced bone mineral density (BMD). This may in turn result in the development of osteopenia or osteoporosis. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown. Because bone development is crucial during the pediatric period, bone health should be a primary concern for all patients receiving high-dose inhaled corticosteroids and/or frequent courses of systemic corticosteroids. Major risk factors for decreased BMD include family history of osteoporosis, prolonged immobilization, tobacco use, malnutrition, and use of other chronic drugs that may reduce bone mass (e.g., anticonvulsants, oral corticosteroids). Caregivers of patients with risk factors should be counseled on age appropriate calcium and vitamin D intake. Due to a systemic absorption of less than 2% after appropriate use, adverse bone effects on bone are not expected with intranasal fluticasone therapy.

Hypersensitivity reactions (e.g., anaphylactoid reactions, angioedema, flushing, and urticaria) have occurred rarely after treatment with topical, intranasal, and orally inhaled fluticasone. Fluticasone inhalation powder contains lactose; use of the dry powder inhaler in persons with severe milk protein hypersensitivity has been associated, rarely, with anaphylactoid reactions.

In rare cases, patients on inhaled fluticasone may present with eosinophilia and clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition often treated with systemic corticosteroids. These events have happened most commonly in association with systemic corticosteroid withdrawal in conjunction with the introduction of inhaled fluticasone therapy. Patients presenting with eosinophilia, vasculitis with granulomas, worsening pulmonary symptoms, and/or neuropathy may have this condition, which may be severe. Similar cases have been reported with the use of other inhaled corticosteroids. A causal relationship to fluticasone has not yet been established; however, consistent with findings in clinical trails, systemic eosinophilic conditions have been reported in rare cases in patients on inhaled fluticasone in postmarketing reports.

Headache (2% to 16%) is the most frequently reported nervous system adverse event associated with the use of fluticasone therapy. During clinical trials, persons receiving treatment with inhaled fluticasone also reported experiencing symptoms such as malaise and/or fatigue (16%), dizziness (1% to 3%), migraine, and sleep disturbances or insomnia. Events observed during clinical practice include: agitation, aggression, anxiety, depression, paralysis of cranial nerves, mood disorders, and restlessness. Also noted, behavioral changes including hyperactivity and irritability were reported very rarely and primarily in children.

Patients receiving inhaled and intranasal fluticasone during clinical trials have reported adverse events affecting the musculoskeletal system. These adverse effects included arthralgia and articular rheumatism (17%), musculoskeletal pain (2% to 12%), muscle injury (5% or less), back pain (1% to 3%), muscle cramps, muscle inflammation, muscle spasms, muscle rigidity, and procedural pain (3% or less). When transitioning from systemic corticosteroids to inhaled corticosteroids, some patients experience joint and/or muscle pain as a symptom of withdrawal from the systemic corticosteroid; carefully evaluate any patient with musculoskeletal symptoms who is transitioning off of systemic therapy.

Adverse reactions affecting the respiratory tract are common in patients receiving intranasal or inhaled fluticasone. The most common include upper respiratory tract infection (2% to 31%), asthma exacerbation (3% to 7%), sinusitis (4% to 33%), throat irritation (10% or less), bronchitis (1% to 12%), cough (9% or less), hoarseness and dysphonia (2% to 9%), epistaxis ( 1% to 7%), nasal congestion (16%), pharyngitis (3% to 25%), rhinitis (13% or less), pharyngolaryngeal pain (3% to 4%), oropharyngeal pain (4% or less), nasopharyngitis (5% to 13%), rhinorrhea (1% to 3%), blood in nasal secretions (1% to 3%), upper respiratory inflammation (2% to 5%), and nasal excoriation or ulcer (1%). Other adverse reactions reported with the use of inhaled or intranasal fluticasone included anosmia or loss of smell, pneumonia, laryngitis, rhinalgia, ear/nose/throat polyps, aphonia, nasal dryness, nasal burning, nasal irritation, nasal soreness, bronchospasm, chest tightness, dyspnea, and wheezing. Nasal septum perforation is a rare, but severe complication of intranasal steroids. Respiratory symptoms related to topical fluticasone are unlikely; however sinus infection, rhinitis, and cough have been reported. If pulmonary symptoms occur during treatment with fluticasone, health care providers are advised to administer treatment, such as a fast-acting inhaled bronchodilator, to the patient.

Miscellaneous adverse reactions potentially related to fluticasone therapy that have been reported include fever (1% to 7%), hyperglycemia, changes in appetite, cholecystitis, edema, palpitations, and weight gain. Fever and extrasystole were reported in 3% or more of patients treated with the combination of fluticasone furoate and a long-acting beta-agonist during clinical trials.

Bleeding, leukopenia, and thrombocytopenia have been reported during postmarketing use of topical fluticasone. Neither the frequency nor a definitive causal relationship to topical fluticasone can be established.

Use of fluticasone does not contraindicate administration of live-virus vaccines. According to the Advisory Committee on Immunization Practices (ACIP), administration of live-virus vaccines is safe and effective when steroid therapy is administered topically or by inhalation.

Fluticasone is contraindicated for use in anyone who is hypersensitive to the medication or any components of the products. Although true corticosteroid hypersensitivity is rare, it can occur and cross-hypersensitivity to other corticosteroids is possible. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which may help to determine whether hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and after the administration of any corticosteroid. Fluticasone inhalation powder products (Flovent Diskus, Armonair Respiclick, Armonair Digihaler, and Arnuity Ellipta) are contraindicated in patients with severe milk protein hypersensitivity; these formulations contain lactose and have been associated, rarely, with anaphylactoid reactions.

Inhaled formulations of fluticasone are contraindicated for the primary treatment of patients with status asthmaticus or other types of acute bronchospasm for which intensive therapy is warranted. Patients should be advised that fluticasone is not to be used as a bronchodilator and is not indicated for relief of acute bronchospasm. Patients should be instructed to contact their physicians immediately when episodes of asthma that are not responsive to bronchodilators occur. During such episodes, patients may require therapy with oral corticosteroids. Although inhaled corticosteroids (ICSs) are not indicated for primary treatment of an acute exacerbation, they may be initiated at any time during an exacerbation for patients not using long-term control therapy. An ICS may also be continued during an exacerbation for patients previously using the drug for chronic control.

Systemic absorption of topical or inhaled fluticasone may result in varying complications depending on the clinical situation and type of administration. In some cases, fluticasone may not produce systemic concentrations high enough to avoid adrenocortical insufficiency in patients transitioning from systemic corticosteroids; however, topical and inhaled steroids have resulted in complications such as hypothalamic-pituitary-adrenal (HPA) suppression in other patients. Use fluticasone with caution when substituting it for oral corticosteroid administration; deaths due to adrenal insufficiency have been reported in asthma patients during and after such a change. Patients receiving fluticasone may require initiation or resumption of systemic corticosteroids during periods of stress or during severe asthma attacks. Systemic absorption of topical or inhaled corticosteroids has produced reversible HPA suppression, manifestations of Cushing's syndrome, hyperglycemia, and glycosuria in some patients. Use fluticasone with caution in patients with underlying Cushing's syndrome. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of topical, intranasal, and orally inhaled corticosteroids in pediatric patients. Concomitant intranasal corticosteroid use and a forced expiratory volume (FEV1)/forced vital capacity (FVC) < 80% has been linked to an increased incidence of HPA suppression in pediatric asthma patients on inhaled corticosteroid therapy. Patients with poor adherence to corticosteroid therapy had a negative risk. With topical corticosteroid use, infants and children may absorb proportionally larger amounts of drug due to a larger skin surface area to body weight ratio, increasing systemic absorption. Other factors that may increase the systemic absorption of topical corticosteroids include: prolonged use, use over larger surface areas or where the epidermal barrier is disrupted (i.e., skin abrasion), or with the use of an occlusive dressing (including diapers and plastic pants) over the application site. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. If signs of HPA suppression occur with the use of intranasal corticosteroids, the drug should be slowly discontinued. Asthmatic children on inhaled corticosteroids should be appropriately monitored. There may be an increased risk of HPA suppression in patients with low body mass index (BMI); some experts recommend adrenal screening in this population. If HPA suppression occurs with any fluticasone formulation, patients will require systemic corticosteroids during periods of physiologic stress. If surgery is required, patients should notify all health care providers that they have received corticosteroids within the last 12 months. Infrequently, signs and symptoms of corticosteroid withdrawal may occur, requiring supplemental systemic corticosteroids.

Topical and inhaled corticosteroids, such as fluticasone, should be used with caution in patients with diabetes mellitus. Exacerbation of diabetes and hyperglycemia may occur with systemic absorption of the topical corticosteroid. Use of topical corticosteroids may further delay healing of skin ulcers in diabetic patients.

As with any long-term topical treatment of the nasal cavity, patients using fluticasone intranasally over several months or longer should be examined periodically for possible changes in the nasal mucosa. Further, because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal perforation or ulcer, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred. Nasal ulceration and nasal septal perforation have been associated with nasal fluticasone use.

The incidence or course of acute viral or bacterial infection is probably minimally affected by inhaled corticosteroids in most immunocompetent individuals. However, the use of inhaled or topical fluticasone in the presence of infection, including tuberculosis of the skin, active or latent tuberculosis of the respiratory tract, untreated systemic or cutaneous fungal, bacterial, parasitic, or viral infection (e.g., herpes infection, measles, or varicella), or ocular herpes infection should be initiated or continued cautiously, if at all. Because of the potential for worsening infection, fluticasone therapy may need to be interrupted during some active infections. Chickenpox and measles can have a more serious or even fatal course in susceptible children using corticosteroids; the exact risk associated with inhaled or topical fluticasone is unclear. If an unimmunized patient is exposed to chickenpox or measles, proper prophylaxis may be indicated. Corticosteroid therapy can reactivate tuberculosis and should not be used except when chemoprophylaxis is instituted concomitantly. The use of nasal or orally inhaled fluticasone may result in localized fungal infection of the nose, mouth, and pharynx with Candida albicans. Instruct patients to rinse their mouth after each use of orally inhaled fluticasone to minimize risk. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic antifungal therapy while still continuing fluticasone therapy; temporary interruption of inhaler use should only be done under close medical supervision. Patients using fluticasone nasal spray for extended periods (i.e., months) should be examined periodically for evidence of infection or other adverse effects on the nasal mucosa.

Detrimental effects on bone metabolism are expected to be much lower with inhaled compared to systemically-administered corticosteroids. However, some data suggest that high-dose inhaled steroids may also decrease bone formation and increase resorption, and decreases in bone mineral density have been reported in patients receiving long-term therapy of inhaled corticosteroids. Because bone development is critical in pediatric patients, monitoring is warranted in patients receiving high-doses or chronic corticosteroid treatment. Patients receiving inhaled steroids, such as fluticasone, may be at increased risk of bone loss compared to healthy individuals; compounding risk factors include preexisting osteopenia, prolonged immobilization, family history of osteoporosis, tobacco smoking, malnutrition, and use of other medications that may reduce bone mass. Due to a systemic absorption of < 2% after appropriate use, adverse effects on bone are not expected with intranasal fluticasone therapy; however, there may be potential in susceptible individuals or when used in high doses.

Use orally inhaled or intranasal fluticasone cautiously in patients with moderate or severe hepatic disease; monitor patients closely for corticosteroid-related adverse effects. Fluticasone is predominately cleared by hepatic metabolism and impairment of liver function may lead to fluticasone accumulation. During clinical trials, systemic exposure of fluticasone furoate oral inhalation increased by up to 3-fold in patients with hepatic impairment compared to healthy patients. After intranasal fluticasone administration, most of the drug is absorbed after being swallowed and undergoes extensive first-pass metabolism through the liver. Results from a single dose study in patients with moderate hepatic impairment (Child-Pugh Class B) indicated markedly increased maximum concentration (Cmax) and systemic drug exposure (area under the curve [AUC]) values. This increased drug exposure resulted in an approximately 20% reduction in serum cortisol concentrations in the hepatically impaired patients when compared to healthy subjects.

As with other potent fluorinated topical corticosteroids, fluticasone creams and ointments should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis. Fluticasone may aggravate these conditions. Fluticasone topical preparations are not recommended to be applied to the face. Topical corticosteroids should not be used in patients with evidence of pre-existing skin atrophy or infection. Use fluticasone preparations cautiously in patients with markedly impaired circulation or peripheral vascular disease due to the potential for skin ulcer. Use of lower potency topical corticosteroids may be necessary in some patients.

Take care to avoid ocular exposure and use around the eyes; cases of visual impairment and ocular hypertension have been reported with topical corticosteroids. Glaucoma, increased intraocular pressure, and cataracts have been reported with long-term use of nasal and inhaled corticosteroids. Consider referral to an ophthalmologist in patients who develop ocular symptoms or who use fluticasone long term.

Fluticasone lotion and cream should not be used in individuals with formaldehyde hypersensitivity. In these patients, the use of fluticasone may prevent healing or worsen dermatitis. The lotion and cream formulations contain the excipient imidurea, which releases formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin.

Marked decrease in skin thickness and delayed skin recovery have been noted in cutaneous areas exposed to sun after the topical application of corticosteroids. Patients that apply fluticasone lotion to exposed portions of the body should avoid excessive sunlight (UV) exposure, both natural and artificial.

Orally inhaled or intranasal corticosteroids may cause growth inhibition in pediatric patients; linear growth retardation has also been reported in pediatric patients after prolonged use of topical corticosteroids. Although data suggest that the effects on growth are minimal, the lowest effective dose of any corticosteroid dosage form should be utilized and growth should be routinely monitored during use. In general, the benefits of regular inhaled corticosteroid (ICS) use outweigh the potential risk of relatively small and non-cumulative growth suppression in children with asthma. The National Asthma Education and Prevention Program Expert Panel warns that prolonged use (e.g., > 1 year) of high doses of ICS, especially when used in combination with frequent courses of systemic corticosteroids, may increase the risk of adverse growth effects. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients. Controlled clinical studies have shown that ICS may cause a mean reduction in growth velocity of approximately 1 centimeter (cm) per year (range: 0.3-1.8 cm/year) and that this reduction appears to depend on dose and duration of exposure. While not specifically addressing fluticasone, the Childhood Asthma Management Program (CAMP) trial suggested that ICS use to control asthma in children may affect final adult height (median follow-up 7 years) by approximately 1 cm. Meta-analysis suggests regular use of low or medium daily dose ICS is associated with a mean reduction of 0.48 cm per year in linear growth velocity (14 trials, n = 5717; 95% CI -0.65 to -0.3, p < 0.0001) and a 0.61 cm change from baseline in height (15 trials, n = 3275; 95% CI -0.83 to -0.38, p < 0.00001) in children with mild to moderate asthma during a 1 year treatment period. Specifically, fluticasone 100-200 mcg/day caused a mean reduction in growth velocity of 0.39 cm per year (5 trials, n = 1405; 95% CI -0.63 to -0.15). This effect appears to be less pronounced subsequent to the first year of therapy and is not cumulative. In addition, a mean difference of -0.2 cm (n = 728; 95% CI 0.02-0.39) in growth velocity within the first year has been observed between low (50-100 mcg/day beclomethasone equivalent; 5.94 cm/year) and medium (200 mcg/day beclomethasone equivalent; 5.74 cm/year) dose ICS, indicating lower growth velocity in the those treated with higher dose ICS. Intranasal corticosteroids may also affect growth. Children (age range: 3-9 years) receiving 200 mcg/day of fluticasone propionate nasal spray were found to have a point estimate for growth velocity of 0.14 cm/year lower than children receiving placebo (95% CI ranging from 0.54 cm/year lower than placebo to 0.27 cm/year higher than placebo). Additionally, data from a 1-year placebo-controlled clinical growth study in children (age range: 5-8.5 years) receiving fluticasone furoate nasal spray 110 mcg/day showed a lower mean growth velocity compared with placebo (mean treatment difference -0.27 cm/year [95% CI -0.48 to -0.06]).

In utero exposure to corticosteroids may result in hypoadrenalism. Monitor neonates of mothers receiving corticosteroids during pregnancy carefully.

Description: Fluticasone is a synthetic fluorinated corticosteroid. Fluticasone is available in products administered topically, intranasally, and via oral inhalation; many products are available for use in pediatric patients. Topical products are mostly of medium-potency and are used to relieve the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and psoriasis. Fluticasone 0.005% ointment and 0.05% cream are usually described as potent topical products. Fluticasone nasal sprays are effective for symptoms of nonallergic rhinitis, as well as seasonal and perennial allergic rhinitis and related symptoms of allergic conjunctivitis. Rhinitis guidelines strongly recommend intranasal corticosteroids as the preferred medication when choosing monotherapy for persistent allergic rhinitis; they may also be offered as first-line therapy for nonallergic rhinitis (NAR) although intranasal antihistamines are strongly recommended as a first-line monotherapy option for NAR. Fluticasone oral inhalation products are used for the maintenance treatment of asthma. Inhaled corticosteroids (ICSs) are the preferred pharmacologic treatment in the long-term management of persistent asthma for most patients. Maintenance ICS therapy may also decrease the frequency and severity of exercise-induced bronchoconstriction (EIB); short-acting beta-2 agonists (SABAs) also help prevent EIB but tolerance can develop with regular SABA use. FDA-approval in pediatric populations differs depending on the specific fluticasone product; some topical formulations are FDA-approved in infants as young as 3 months, and some nasal sprays are approved in pediatric patients 2 years and older. Twice-daily fluticasone propionate oral inhalations are approved in patients as young as 4 years old and the once-daily fluticasone furoate oral inhalation is approved in patients 5 years and older.

INHALED DOSAGE RANGES BY PRODUCT
The ranges presented help define low, medium, and high ICS daily dosing according to asthma treatment recommendations. The NAEPP 2020 focused updates state that ICS ranges from the NAEPP 2007 guidelines need to be updated in future NAEPP guidance.

Fluticasone propionate (standard particle size HFA)
Children 1 to 3 years:
-GINA: Not available
-NAEPP-Low Dose: 176 mcg
-Medium Dose: more than 176 mcg and up to 352 mcg
-High Dose: more than 352 mcg


Children 4 years:
-GINA-Low Dose: 50 mcg
-Medium Dose: Not available
-High Dose: Not available

-NAEPP-Low Dose: 176 mcg
-Medium Dose: more than 176 mcg and up to 352 mcg
-High Dose: more than 352 mcg


Children 5 years:
-GINA-Low Dose: 50 mcg
-Medium Dose: Not available
-High Dose: Not available

-NAEPP-Low Dose: 88 mcg to 176 mcg
-Medium Dose: more than 176 mcg and up to 352 mcg
-High Dose: more than 352 mcg


Children 6 to 11 years:
-GINA-Low Dose: 50 mcg to 100 mcg
-Medium Dose: more than 100 mcg and up to 200 mcg
-High Dose: greater than 200 mcg

-NAEPP-Low Dose: 88 mcg to 176 mcg
-Medium Dose: more than 176 mcg and up to 352 mcg
-High Dose: more than 352 mcg


Children and Adolescents 12 years and older:
-GINA-Low Dose: 100 mcg to 250 mcg
-Medium Dose: more than 250 mcg and up to 500 mcg
-High Dose: more than 500 mcg

-NAEPP-Low Dose: 88 mcg to 264 mcg
-Medium Dose: more than 264 mcg and up to 440 mcg
-High Dose: more than 440 mcg


Fluticasone propionate dry powder inhaler (DPI)
Children 4 years and younger: Not available

Children 5 years:
-GINA: Not available
-NAEPP-Low Dose: 100 mcg to 200 mcg
-Medium Dose: more than 200 mcg and up to 400 mcg
-High Dose: more than 400 mcg


Children 6 to 11 years:
-GINA-Low Dose: 50 mcg to 100 mcg
-Medium Dose: more than 100 mcg and up to 200 mcg
-High Dose: more than 200 mcg

-NAEPP-Low Dose: 100 mcg to 200 mcg
-Medium Dose: more than 200 mcg and up to 400 mcg
-High Dose: more than 400 mcg


Children and Adolescents 12 years and older:
-GINA-Low Dose: 100 mcg to 250 mcg
-Medium Dose: more than 250 mcg and up to 500 mcg
-High Dose: more than 500 mcg

-NAEPP-Low Dose: 100 mcg to 300 mcg
-Medium Dose: more than 300 and up to 500 mcg
-High Dose: more than 500 mcg


Fluticasone furoate dry powder inhaler (DPI)
Children 1 to 5 years: Not available

Children 6 to 11 years:
-GINA-Low Dose: 50 mcg
-Medium Dose: 50 mcg
-High Dose: Not available

-NAEPP: Not available

Children and Adolescents 12 years and older:
-GINA-Low Dose: 100 mcg
-Medium Dose: 100 mcg
-High Dose: 200 mcg

-NAEPP: Not available

For asthma maintenance treatment:
Respiratory (Inhalation) dosage (fluticasone propionate aerosol suspension; e.g., Flovent HFA):
Children 1 to 3 years*: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily, approximately 12 hours apart, is the recommended and maximum dosage that has been used with a spacer device with mask. If regimen fails to provide adequate control, reassess treatment and consider additional therapeutic options. Titrate to the lowest effective dose once asthma stability is achieved.
Children 4 to 11 years: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily, approximately 12 hours apart, is the recommended and maximum dosage. If regimen fails to provide adequate control, reassess treatment and consider additional therapeutic options. Titrate to the lowest effective dose once asthma stability is achieved.
Children and Adolescents 12 to 17 years: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth twice daily, approximately 12 hours apart, for patients not currently on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. May increase the dose after 2 weeks if the response is not adequate. Max: 880 mcg (4 actuations of 220 mcg/actuation) twice daily. Titrate to the lowest effective dose once asthma stability is achieved.
Respiratory (Inhalation) dosage (fluticasone propionate inhalation powder; e.g., Flovent Diskus):
Children 4 to 11 years: 50 mcg (1 actuation of 50 mcg/actuation) inhaled by mouth twice daily, approximately 12 hours apart. Larger initial doses may be considered for patients with poor asthma control or who have previously required high doses of inhaled corticosteroids. May increase the dose after 2 weeks if the response is not adequate. Max: 100 mcg (2 actuations of 50 mcg/actuation or 1 actuation of 100 mcg/actuation) twice daily. Titrate to the lowest effective dose once asthma stability is achieved.
Children and Adolescents 12 to 17 years : 100 mcg (1 actuation of 100 mcg/actuation) inhaled by mouth twice daily, approximately 12 hours apart. Larger initial doses may be considered for patients with poor asthma control or who have previously required high doses of inhaled corticosteroids. May increase the dose after 2 weeks if the response is not adequate. Max: 1,000 mcg (4 actuations of 250 mcg/actuation) twice daily. Titrate to the lowest effective dose once asthma stability is achieved.
Respiratory (Inhalation) dosage (fluticasone furoate inhalation powder; i.e., Arnuity Ellipta):
Children 5 to 11 years: 50 mcg (1 actuation of 50 mcg/actuation) inhaled by mouth once daily is the recommended initial and maximum dose.
Children and Adolescents 12 to 17 years: 100 mcg (1 actuation of 100 mcg/actuation) inhaled by mouth once daily for patients not currently on an inhaled corticosteroid. Larger initial doses may be considered for patients with poor asthma control or who have previously required high doses of inhaled corticosteroids. May increase the dose after 2 weeks if the response is not adequate. Max: 200 mcg (2 actuations of 100 mcg/actuation or 1 actuation of 200 mcg/actuation) once daily. Titrate to the lowest effective dose once asthma stability is achieved.
Respiratory (Inhalation) dosage (fluticasone propionate inhalation powder; e.g., Armonair Digihaler):
Children 4 to 11 years: 30 mcg (1 actuation of 30 mcg/actuation) inhaled by mouth twice daily for patients not currently on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. May increase the dose after 2 weeks if the response is not adequate. Max: 55 mcg (1 actuation of 55 mcg/actuation) twice daily. Titrate to the lowest effective dose once asthma stability is achieved.
Children and Adolescents 12 to 17 years: 55 mcg (1 actuation of 55 mcg/actuation) inhaled by mouth twice daily for patients not currently on an inhaled corticosteroid. Base starting dosage on previous asthma therapy and asthma severity. May increase the dose after 2 weeks if the response is not adequate. Max: 232 mcg (1 actuation of 232 mcg/actuation) twice daily. Titrate to the lowest effective dose once asthma stability is achieved.

For the treatment of transient increase in bronchospasm* (e.g., episodic wheezing) as asthma reliever therapy:
Respiratory (Inhalation) dosage (fluticasone propionate inhalation aerosol; e.g., Flovent HFA):
Children 6 to 11 years: 88 mcg (2 actuations of 44 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-2 agonist (SABA) is given. NAEPP does not recommend intermittent as-needed inhaled corticosteroid (ICS)/SABA therapy in this age group because therapy has not been adequately studied.
Children and Adolescents 12 to 17 years: 88 mcg (2 actuations of 44 mcg/actuation), 110 mcg (1 actuation of 110 mcg/actuation), or 220 mcg (2 actuations of 110 mcg/actuation or 1 actuation of 220 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-2 agonist (SABA) is given. NAEPP only recommends as-needed inhaled corticosteroid (ICS)/SABA as an option for persons with mild persistent asthma.
Respiratory (Inhalation) dosage (fluticasone propionate inhalation powder; i.e., Flovent Diskus):
Children 6 to 11 years: 100 mcg (1 actuation of 100 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-2 agonist (SABA) is given. NAEPP does not recommend intermittent as-needed inhaled corticosteroid (ICS)/SABA therapy in this age group because therapy has not been adequately studied.
Children and Adolescents 12 to 17 years: 100 mcg (1 actuation of 100 mcg/actuation) or 250 mcg (1 actuation of 250 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-2 agonist (SABA) is given. NAEPP only recommends as-needed inhaled corticosteroid (ICS)/SABA as an option for persons with mild persistent asthma.
Respiratory (Inhalation) dosage (fluticasone furoate inhalation powder; i.e., Arnuity Ellipta):
Children and Adolescents 12 to 17 years: 100 mcg (1 actuation of 100 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-2 agonist (SABA) is given. NAEPP only recommends as-needed inhaled corticosteroid (ICS)/SABA as an option for persons with mild persistent asthma.
Respiratory (Inhalation) dosage (fluticasone propionate inhalation powder; e.g., Armonair Digihaler):
Children 6 to 11 years: 30 mcg (1 actuation of 30 mcg/actuation) or 55 mcg (1 actuation of 55 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-2 agonist (SABA) is given. NAEPP does not recommend intermittent as-needed inhaled corticosteroid (ICS)/SABA therapy in this age group because therapy has not been adequately studied.
Children and Adolescents 12 to 17 years: 113 mcg (1 actuation of 113 mcg/actuation) or 232 mcg (1 actuation of 232 mcg/actuation) inhaled by mouth as needed whenever a short-acting beta-2 agonist (SABA) is given. NAEPP only recommends as-needed inhaled corticosteroid (ICS)/SABA as an option for persons with mild persistent asthma.

For exercise-induced bronchospasm prophylaxis*:
Oral Inhalation dosage (fluticasone propionate inhalation aerosol suspension; i.e., Flovent HFA):
Children 4 to 11 years: 88 mcg (2 oral inhalations of 44 mcg/actuation) twice daily is the usual and max dosage for controller therapy. Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
Children and Adolescents 12 to 17 years: 88 mcg (2 oral inhalations of 44 mcg/actuation) twice daily is a usual initial dose for controller therapy. FDA-approved Max: 4 oral inhalations of 220 mcg/actuation twice daily (880 mcg twice daily). Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
Oral inhalation powder dosage (i.e., Flovent Diskus):
Children 4 to 11 years: 50 mcg (1 oral inhalation of 50 mcg/actuation) twice daily is a usual initial dose for controller therapy. FDA-approved Max: 1 oral inhalation of 100 mcg/actuation twice daily (100 mcg twice daily). Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
Children and Adolescents 12 to 17 years: 100 mcg (1 oral inhalation of 100 mcg/actuation) twice daily is a usual initial dose for controller therapy. FDA-approved Max: 4 oral inhalations of 250 mcg/actuation twice daily (1,000 mcg twice daily). Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
Oral Inhalation dosage (fluticasone furoate inhalation powder; i.e., Arnuity Ellipta):
Children 5 to 11 years: 50 mcg (1 oral inhalation of 50 mcg/actuation) once daily, at the same time each day, is the recommended and max dose for controller therapy. Regular ICS (controller) use reduces the incidence of EIB.
Children and Adolescents 12 to 17 years: 100 mcg (1 oral inhalation of 100 mcg/actuation) once daily, at the same time each day, is a usual initial dose for controller therapy. FDA-approved Max: 1 oral inhalation of 200 mcg/actuation once daily (200 mcg once daily). Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
Oral Inhalation dosage (fluticasone propionate inhalation powder; e.g., Armonair Digihaler):
Children and Adolescents 12 to 17 years: 55 mcg (1 oral inhalation of 55 mcg/actuation) twice daily is a usual initial dose for controller therapy. FDA-approved Max: 1 oral inhalation of 232 mcg/actuation twice daily (232 mcg twice daily). Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.
Children 4 to 11 years: 30 mcg (1 oral inhalation of 30 mcg/actuation) twice daily is a usual initial dose for controller therapy. FDA-approved Max: 1 oral inhalation of 55 mcg/actuation twice daily (55 mcg twice daily). Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.

For the treatment of corticosteroid-responsive dermatoses including atopic dermatitis, localized vitiligo, eczema, lichen planus, and localized bullous pemphigoid, phimosis, and psoriasis:
-for the general treatment of corticosteroid-responsive dermatoses:
Topical dosage (cream):
Infants, Children, and Adolescents 3 months to 17 years: Apply a thin layer topically to the affected skin area(s) 2 times daily for up to 4 weeks. If no improvement within 2 weeks, reassess diagnosis.
-for the treatment of atopic dermatitis:
Topical dosage (cream):
Infants, Children, and Adolescents 3 months to 17 years: Apply a thin layer topically to the affected skin area(s) once or twice daily until symptoms resolve for up to 4 weeks. If no response is seen within 2 weeks, reassess diagnosis. Proactive, intermittent application of topical corticosteroids 1 to 2 times weekly to areas that commonly flare is recommended to help prevent relapses.
Topical dosage (lotion):
Children and Adolescents: Apply a thin layer topically to the affected skin area(s) once daily until symptoms resolve for up to 4 weeks. If no improvement within 2 weeks, reassess diagnosis. Proactive, intermittent application of topical corticosteroids 1 to 2 times weekly to areas that commonly flare is recommended to help prevent relapses.
-for the treatment of psoriasis:
Topical dosage (cream):
Infants, Children, and Adolescents 3 months to 17 years: Apply a thin layer topically to the affected skin area(s) 2 times daily. If no improvement within 2 weeks, reassess diagnosis. Guidelines recommend topical corticosteroids as monotherapy for short-term treatment of localized psoriasis.

For the management of symptoms associated with seasonal allergies or perennial allergies, including allergic rhinitis and allergic conjunctivitis:
Nasal dosage (fluticasone furoate 27.5 mcg/spray; OTC Flonase Sensimist):
Children 2 to 11 years: 1 spray per nostril once daily (55 mcg/day). Use for the shortest amount of time necessary to achieve symptom relief. For OTC products: after 2 months of daily use per year, a healthcare professional should be consulted.
Children and Adolescents 12 to 17 years: 2 sprays per nostril once daily (110 mcg/day) during week 1. After 1 week, 1 to 2 sprays per nostril once daily (55 to 110 mcg/day) may be used as needed. For OTC products: after 6 months of use, a healthcare professional should be consulted.
Nasal dosage (fluticasone propionate 50 mcg/spray; e.g., OTC Flonase Allergy Relief):
Children 4 to 11 years: 1 spray per nostril once daily (100 mcg/day). Use for the shortest amount of time necessary to achieve symptom relief. Max: 1 spray per nostril daily (100 mcg/day). For OTC products: after 2 months of daily use per year, a healthcare professional should be consulted.
Children and Adolescents 12 to 18 years: 2 sprays per nostril once daily (200 mcg/day) initially. After 1 week, 1 to 2 sprays per nostril once daily (100 to 200 mcg/day) may be used as needed. For OTC products: after 6 months of use, a healthcare professional should be consulted.

For the management of nasal symptoms associated with vasomotor rhinitis (perennial nonallergic rhinitis):
Nasal dosage (fluticasone propionate nasal spray 50 mcg/spray; Rx-only):
Children and Adolescents 4 to 17 years: 1 spray per nostril once daily (100 mcg/day). May increase to 2 sprays per nostril once daily (200 mcg/day). When adequate response achieved, reduce to 1 spray per nostril once daily (100 mcg/day). Max: 2 sprays per nostril daily (200 mcg/day).

For the treatment of eosinophilic esophagitis*:
Oral dosage (fluticasone propionate inhalation aerosol; e.g. Flovent HFA):
Children and Adolescents: 88 (2 actuations of 44 mcg/actuation) to 440 mcg (2 actuations of 220 mcg/actuation) PO (swallowed) 2 to 4 times daily for 8 weeks, then reduce dose to the lowest dose that maintains remission.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
1 to 2 months: Safety and efficacy have not been established.
3 months and older: Twice daily application for cream; once daily application for lotion. Safety and efficacy have not been established for other formulations.
-Children
1 year: Twice daily application for cream; once daily application for lotion. Safety and efficacy have not been established for other formulations; however, doses more than 352 mcg/day from the fluticasone propionate MDI have been used off-label for asthma.
2 to 3 years: Twice daily application for cream; once daily application for lotion; 55 mcg/day intranasally for fluticasone furoate. Safety and efficacy have not been established for other formulations; however, doses more than 352 mcg/day from the fluticasone propionate MDI have been used off-label for asthma.
4 years: Twice daily application for cream; once daily application for lotion; 55 mcg/day intranasally for fluticasone furoate; 200 mcg/day intranasally for fluticasone propionate; 200 mcg/day via fluticasone propionate dry powder inhaler (DPI) Flovent Diskus; 110 mcg/day via fluticasone propionate DPI Armonair Digihaler; 176 mcg/day via fluticasone propionate MDI per FDA-approved labeling. Doses more than 352 mcg/day from the fluticasone propionate MDI have been used off-label for asthma. Safety and efficacy of fluticasone furoate DPI have not been established.
5 to 11 years: Twice daily application for cream; once daily application for lotion; 55 mcg/day intranasally for fluticasone furoate; 200 mcg/day intranasally for fluticasone propionate; 200 mcg/day via fluticasone propionate dry powder inhaler (DPI) Flovent Diskus; 176 mcg/day via fluticasone propionate MDI; 110 mcg/day via fluticasone propionate DPI Armonair Digihaler; 50 mcg/day via fluticasone furoate DPI per FDA-approved labeling. Doses more than 352 mcg/day from the fluticasone propionate MDI and more than 400 mcg/day from the fluticasone propionate DPI Flovent Diskus have been used off-label for asthma.
12 years: Twice daily application for cream; once daily application for lotion; 110 mcg/day intranasally for fluticasone furoate; 200 mcg/day intranasally for fluticasone propionate; 2,000 mcg/day via fluticasone propionate dry powder inhaler (DPI) Flovent Diskus; 464 mcg/day via fluticasone propionate DPI Armonair Digihaler; 200 mcg/day via fluticasone furoate DPI; 1,760 mcg/day via fluticasone propionate MDI.
-Adolescents
Twice daily application for cream; once daily application for lotion; 110 mcg/day intranasally for fluticasone furoate; 200 mcg/day intranasally for fluticasone propionate; 2,000 mcg/day via fluticasone propionate dry powder inhaler (DPI) Flovent Diskus; 464 mcg/day via fluticasone propionate DPI Armonair Digihaler; 200 mcg/day via fluticasone furoate DPI; 1,760 mcg/day via fluticasone propionate MDI.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; however, caution is recommended in those with moderate to severe hepatic impairment.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme that causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.

Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV1, peak-flow rate, and respiratory symptoms. Because corticosteroid effects take several hours to days to become clinically noticeable, they are ineffective for primary treatment of severe acute bronchospastic attacks or for status asthmaticus. Inhaled corticosteroids have no bronchodilatory properties. In the treatment of asthma, orally inhaled corticosteroids block the late phase allergic response to allergens. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes.

In the treatment of allergies, intranasal fluticasone reduces allergic responses of several cell types (e.g., mast cells and eosinophils) involved in the allergic response by the same cellular mechanism as the topical corticosteroids. Clinically, symptoms such as rhinorrhea and postnasal drip, nasal congestion, sneezing, and pharyngeal itching are reduced. In vitro studies indicate that the binding affinity of fluticasone furoate for the human glucocorticoid receptor is 1.7 and 29.9 times that of fluticasone propionate and dexamethasone, respectively. The clinical significance of these findings is unknown.

Pharmacokinetics: Fluticasone is administered by oral inhalation, intranasal spray, or by topical application to the skin. Based on studies using intravenous fluticasone propionate, the average volume of distribution (Vd) is 4.2 L/kg (range 2.3 to 16.7 L/kg) and distribution is rapid because of high lipid solubility and tissue binding. Protein binding of fluticasone is more than 90%. The drug is weakly and reversibly bound to erythrocytes and is not significantly bound to human transcortin. Fluticasone is hepatically metabolized via cytochrome P450 3A4. Excretion is primarily in the feces as parent drug and metabolites; less than 5% of a dose is excreted in the urine as metabolites. The terminal elimination half-life of intravenous fluticasone propionate is approximately 7.8 hours while half-life after oral inhalation averages 11.2 hours. The half-life of intravenous fluticasone furoate averages 15 hours while half-life after oral inhalation averages 24 hours.

Affected cytochrome P450 isoenzymes: CYP3A4
The potential for fluticasone to inhibit or induce metabolic enzymes and transporter systems is negligible at low inhalation doses. However, fluticasone is a substrate of CYP3A4, and systemic exposure may increase when coadministered with strong inhibitors of CYP3A4, potentially resulting in a reduction of mean serum cortisol concentrations. Coadministration of inhaled fluticasone propionate and a strong inhibitor of CYP3A4 is not recommended; use caution with inhaled fluticasone furoate.


-Route-Specific Pharmacokinetics
Topical Route
While systemic absorption is usually minimal, topical corticosteroids can penetrate normal intact skin; however, inflammation, skin disease, and occlusive dressing may enhance absorption. Pediatric patients, particularly infants and young children, may be more susceptible to systemic absorption due to their larger skin surface to body mass ratio.

Fluticasone Propionate 0.05% Lotion
In a trial of infants (3 to 11 months of age) with moderate to severe atopic dermatitis who were treated with an exaggerated dosing regimen of fluticasone lotion twice daily (rather than the FDA-approved regimen of once daily) for at least 3 to 4 weeks, 1 of 49 infants showed laboratory evidence of HPA axis suppression. The mean BSA treated was 54%. In another study of 21 pediatric patients (2 to 5 years) with moderate to severe atopic dermatitis who were treated with twice daily fluticasone lotion for at least 3 to 4 weeks, a total of 13 patients (62%) tested had measurable fluticasone plasma concentrations at the end of treatment. The mean fluticasone plasma concentration was 0.16 +/- 0.23 ng/mL; 3 patients (aged 3 to 4 years) had fluticasone concentrations more than 0.3 ng/mL, with 1 patient having a concentration of 0.82 ng/mL.

Fluticasone Propionate 0.05% Cream
In a study of 12 healthy males, 12.5 grams of 0.05% fluticasone propionate cream twice daily for 3 weeks resulted in undetectable plasma concentrations (less than 0.05 ng/mL). In another study of 6 healthy volunteers, 25 grams of the same formulation under occlusion for 5 days yielded plasma concentrations of 0.07 to 0.39 ng/mL.

Fluticasone Propionate 0.005% Ointment
When 25 grams of 0.005% fluticasone propionate ointment was applied to healthy volunteers twice daily for 5 days under occlusion, plasma concentrations ranged from 0.08 to 0.22 ng/mL.

Inhalation Route
Orally inhaled fluticasone acts locally in the lung; therefore, plasma concentrations do not predict therapeutic effect.

Fluticasone Propionate Aerosol (e.g., Flovent HFA)
Oral systemic bioavailability of fluticasone propionate is negligible (less than 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. In contrast, the majority of the drug delivered to the lung is systemically absorbed. In a pharmacokinetic analysis of 215 patients receiving fluticasone metered-dose inhaler (MDI) 88 mcg twice daily, the mean peak plasma concentration (Cmax) at steady state was 20 pg/mL in all age groups (6 to 11 months, 1 to 3 years, and 12 years and older) except those children age 4 to 11 years (Cmax 11 pg/mL). Children less than 4 years of age had drug administered with the assistance of a valved holding chamber (VHC). The lower exposure in children ages 4 to 11 years most likely reflected the inability of this age group to coordinate actuation and inhalation. In a single-dose crossover study in children 4 to 11 years, the use of a VHC resulted in plasma concentrations more than twice those measured after administration without the VHC. Data from patients 12 years of age and older indicated a dose-related increase in systemic exposure. Patients receiving fluticasone MDI 220 mcg (n = 15) or 440 mcg (n = 17) twice daily yielded a mean Cmax of 47.3 pg/mL and 87 pg/mL at steady state, respectively.

Fluticasone Propionate Inhalation Powder (e.g., Flovent Diskus)
Oral systemic bioavailability of fluticasone propionate is negligible (less than 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. In contrast, the majority of the drug delivered to the lung is systemically absorbed. The absolute bioavailability of fluticasone propionate dry powder inhaler (DPI) averages 7.8%. In a clinical study of children ages 4 to 11 years with mild to moderate asthma (n = 61), the mean Cmax after receiving fluticasone DPI 50 or 100 mcg were 5 and 8 pg/mL, respectively. Plasma concentrations at 20 and 40 minutes after dosing were low, ranging from undetectable (80% of samples) to 88 pg/mL.

Fluticasone Furoate Inhalation Powder (e.g., Arnuity Ellipta)
Oral systemic bioavailability of fluticasone furoate is negligible (approximately 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. The absolute bioavailability of fluticasone furoate dry powder inhaler (DPI) is 14%, primarily due to absorption of the inhaled portion of the dose delivered to the lung. Peak plasma concentrations are obtained 0.5 to 1 hour after administration. Systemic exposure (AUC) in subjects with asthma is 26% lower than observed in healthy patients. At steady state, the rate and extent of systemic exposure in children aged 5 to 11 years were comparable to that observed in adult and adolescent patients after dosing with fluticasone furoate 100 mcg monotherapy.

Fluticasone Propionate Inhalation Powder (e.g., Armonair Respiclick)
Oral systemic bioavailability of fluticasone propionate is negligible (approximately 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. In contrast, the majority of the drug delivered to the lung is systemically absorbed. Peak plasma concentrations are obtained 1 hour after administration.

Other Route(s)
Intranasal Route
The average absolute bioavailabilities of intranasal fluticasone propionate and fluticasone furoate are less than 2% and 0.5%, respectively. Most of an intranasal fluticasone dose is swallowed; studies using oral dosing have demonstrated systemic bioavailability is less than 1% due to incomplete absorption in the gut and first pass metabolism in the liver. Plasma concentrations are generally negligible when fluticasone is used at recommended doses. After administration of fluticasone propionate for 3 weeks, plasma concentrations were above the level of detection (50 pg/mL) only when recommended doses were exceeded and then only in occasional samples at low concentrations. After administration of fluticasone furoate 110 mcg intranasally once daily for 12 weeks, concentrations more than 10 pg/mL were observed in less than 16% of children and less than 31% of adolescents. After administration of 55 mcg once daily, less than 7% of children had quantifiable concentrations. A few isolated cases of concentrations more than 500 pg/mL were observed (patient population unspecified). Reasons for the elevated concentrations are unknown, and cortisol concentrations were not affected. Less than 1% of dose-related material is excreted in the urine.


-Special Populations
Hepatic Impairment
Pharmacokinetics of fluticasone may be altered in patients with hepatic impairment. After repeated dosing of orally inhaled fluticasone furoate for 1 week, systemic exposure increased 34%, 83%, and 75% in subjects with mild, moderate, and severe hepatic impairment, respectively, compared to healthy subjects. In patients with moderate impairment receiving 200 mcg/day, mean serum cortisol (0 to 24 hours) was reduced by 34% (90% CI: 11%, 51%) compared to healthy subjects. In patients with severe impairment receiving 100 mcg/day, mean serum cortisol was increased by 14% (90% CI: -16%, 55%) compared to healthy subjects.

Ethnic Differences
During clinical trials, systemic exposure to orally inhaled fluticasone furoate 200 mcg was 27% to 49% higher in healthy patients of Japanese, Korean, and Chinese heritage compared to Caucasian patients. Similar differences were observed in patients with asthma. There is no evidence that this higher exposure results in clinically significant effects on efficacy or urinary cortisol excretion in these racial groups.