24 HOUR ALLERGY (Generic for FLONASE ALLERGY RELIEF)

Fluticasone is a synthetic fluorinated corticosteroid. Fluticasone is available in products administered topically, intranasally, and via oral inhalation; many products are available. 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. Some nasal products are also effective at reducing nasal polyps in adults. Fluticasone oral inhalations are used for the maintenance treatment of asthma or chronic obstructive pulmonary disease (COPD). 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 agonist (SABA)s also help prevent EIB but tolerance can develop with regular SABA use. Fluticasone may be used in combination with an inhaled long-acting beta-2 agonist (LABA) as initial therapy in patients with a high risk of COPD exacerbation. An ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD; however clinical trials failed to demonstrate a statistically significant effect on survival.

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

Route-Specific Administration

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.
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.
-The amount of cream or ointment needed to cover a certain area can be calculated. A 1 gram application of cream covers 100 cm2 of skin. The entire skin surface of the average size adult will be covered by 30 grams of topical steroid cream.
-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.



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. There is no evidence the use of the mobile app leads to improved clinical outcomes, including safety and effectiveness.
-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
NOTE: Different nasal formulations are available; the fluticasone propionate nasal sprays (Flonase delivers 50 mcg/spray and Xhance delivers 93 mcg/spray); fluticasone furoate nasal spray (Flonase Sensimist delivers 27.5 mcg/spray).

General Nasal Administration Information
-Instruct patient on the proper use of the nasal spray.
-Ensure that the proper product has been selected.
-Before using for the first time the unit must be primed. Keep the sprayer pointed away from patient, other people, and pets.
-To avoid the spread of infection, do not use the sprayer for more than one person.

-For fluticasone propionate (e.g., Flonase products): Shake well before each use. Before first use, pump the activator 6 times until a fine wide spray appears. If the unit has not been used for 7 days, re-prime the unit. 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.

-For fluticasone propionate (e.g., Xhance): Shake well before each use. Before first use, prime the unit by first gently shaking and then pressing the bottle 7 times or until a fine mist appears; direct the spray into the air, away from the face. If the unit has not been used for 7 days, re-prime the unit by shaking and releasing 2 sprays, in the same manner. Fluticasone propionate is delivered into the nose by actuating the pump spray into 1 nostril while simultaneously blowing (exhaling) into the mouthpiece of the device. To administer, insert the tapered tip of the cone-shaped nosepiece deep into 1 nostril and form a tight seal between the nosepiece and the nostril. Next, place the flexible mouthpiece into the mouth, bending it as necessary to maintain a tight seal. Blow into the mouthpiece, and while continuing to blow, push the bottle up to actuate the spray pump. Continuing to blow through the mouth, but not inhaling or exhaling through the nose, at the time of actuation is important to achieve intended drug deposition. Repeat the process in the other nostril for a full dose. The unit does not need to be cleaned; if you prefer to clean it, remove the cap and use a clean, dry, lint-free cloth to wipe after each use. Replace the cap and store in a clean, dry place.

-For fluticasone furoate (e.g., Flonase Sensimist): Shake well before each use. Before first use, release 6 test sprays into the air away from face. 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, prime the pump again until a fine mist appears. 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. Discard after 120 sprays, even if the bottle is not empty.

Fluticasone has a relatively low risk of hypothalamic-pituitary-adrenal (HPA) suppression when used at recommended doses. Pharmacologic doses of fluticasone administered for prolonged periods can, however, result in adrenocortical insufficiency. Systemic glucocorticoid adverse effects were not reported during clinical trials with fluticasone nasal spray or oral inhalation when administered at recommended doses. However, manifestations of Cushing's syndrome and hypothalamic-pituitary-adrenal (HPA) suppression with possible adrenocortical insufficiency and withdrawal symptoms after stopping treatment can occur. With topical therapy, such effects are more common if large doses of topical fluticasone are applied over extensive areas, under occlusive dressings, or for prolonged periods of time. Patients applying fluticasone topically to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. Symptoms of hypercorticism (e.g., Cushing's syndrome) may occur if recommended inhaled or nasal doses of fluticasone are exceeded, are used for prolonged periods of time, or if patients are particularly sensitive to the effects of fluticasone. Systemic absorption of fluticasone exerts a negative feedback effect on the pituitary, thereby inhibiting the secretion of adrenocorticotropin (ACTH). This results in a decrease in ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time and route of administration, and duration of therapy. Patients with HPA suppression will require increased doses of corticosteroid therapy during periods of excessive stress. Postmarketing analysis show that Cushingoid features have been observed during clinical practice with the use of topical, nasal, or orally inhaled fluticasone.

Adrenal suppression and growth inhibition have been observed in some children following therapy with high-dose fluticasone propionate inhalations. Postmarketing reports of growth inhibition (i.e., growth velocity reduction) in children and adolescents have been made with fluticasone oral inhalation therapy and other inhaled corticosteroids. 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. With orally inhaled corticosteroids, the mean reduction in growth velocity is approximately one centimeter per year (range 0.3 to 1.8 cm per year) and appears to be related to the dose and duration of exposure. 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. Further study is needed to determine the long-term effects of growth velocity reduction in children, including the impact on final adult height. To minimize the effects of inhaled corticosteroids, each patient should be titrated to the lowest effective dose. Children receiving 200 mcg per day of fluticasone nasal spray were found to have a point estimate for growth velocity of 0.14 cm/year lower than children receiving placebo (95% confidence interval 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 (5 to 8.5 years of age) receiving 110 mcg per day of fluticasone furoate nasal spray showed a lower mean growth velocity compared with placebo (mean treatment difference -0.27 cm/year [CI -0.48 to -0.06]). Retardation of linear growth has also been reported in pediatric patients after prolonged treatment with topical corticosteroids. As with other dosage forms, topical steroids should be applied using the least amount that is compatible with an effective regimen.

Gastrointestinal (GI) adverse events have been experienced by patients receiving treatment with fluticasone. In clinical trials, the most frequently reported GI adverse events included abdominal pain (1% to 3% intranasal, 1% to 4% oral inhalation), abdominal discomfort (1% to less than 3% intranasal), colitis (1% to 3% oral inhalation), diarrhea (1% to 3% intranasal, 1% to 4% oral inhalation, 1% topical), dyspepsia (1% to 3% oral inhalation), nausea (1% to 22% inhaled), and vomiting (1% to 22% inhaled, 1% topical). Other adverse reactions affecting the GI tract included ageusia or loss of taste (intranasal) and xerostomia (intranasal, oral inhalation). Dental caries and tooth discoloration have been reported in postmarketing experience with an orally inhaled fluticasone. Elevated hepatic enzymes (AST and ALT) were reported in 1 patient (4-month-old child) who received fluticasone lotion in clinical trials; an incidence for this potential adverse reaction cannot be established for the general population or with other products.

Children are more prone to systemic adverse effects of topical fluticasone because of larger skin surface area-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. Take measures to avoid excess administration of topical fluticasone. Additionally, increased intracranial pressure has been reported in a patient using nasally inhaled fluticasone and in patients taking systemic/oral steroids. Caution is advised for all dosage forms.

Secondary bacterial, viral, and fungal infections (e.g., influenza (1% to 7%), oropharyngeal candidiasis (2% to 31%), otitis media (1% to 4%), pelvic inflammatory disease (1% to 3%), pneumonia, vaginitis/vulvovaginitis (1% to 3%), viral gastroenteritis (1% to 5%), upper respiratory tract infection (3% to 31), respiratory tract infection (1% to 5%), and urinary tract infection have been observed during treatment with various routes of fluticasone. 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. Using an add-on spacer device, reducing the frequency of use, and rinsing the mouth following use may minimize the incidence of oropharyngeal thrush. Oral candidiasis was reported in 3% of patients receiving fluticasone furoate inhalation powder. Esophageal candidiasis was reported during postmarketing experience with fluticasone propionate inhalation aerosol. Localized Candida albicans infections were also reported during clinical trials with intranasal fluticasone and topical fluticasone. Candida albicans infections (nasal, pharyngeal, esophageal or intestinal) were reported in 0.9% of patients receiving fluticasone nasal spray for treating nasal polyps at durations of 3 to 12 months. Healthcare providers are recommended to perform periodic evaluations for the presence of Candida infections. Additionally, the use of corticosteroids may mask the manifestations of an infection in some patients.

Inhaled or nasal corticosteroid therapy, like fluticasone, has been associated with the development of cataracts, increased intraocular pressure or ocular hypertension, and glaucoma in adults. The risk increases with long-term and high-dose inhaled corticosteroid use. Cataracts usually occur with large doses or therapy duration greater than 6 months. The mechanism of corticosteroid-induced cataract formation is uncertain but may involve disruption of sodium-potassium pumps in the lens epithelium leading to accumulation of water in lens fibers and agglutination of lens proteins. Cataracts were reported in 1.2% of patients treated with fluticasone nasal spray for nasal polyps, compared with 1.9% of patients treated with placebo; two patients in the fluticasone group reported subcapsular cataracts compared with none treated with placebo. Eleven patients (1.2%) in uncontrolled, open-label trials of 3 to 12 months duration developed new or worsening cataracts, of which none were subcapsular. Ocular hypertension was reported in greater than 1%, but less than 3% of patients receiving fluticasone nasal spray. Other ocular adverse reactions associated with inhaled or nasal fluticasone therapy include blurred vision, blepharoconjunctivitis, conjunctivitis (1% to 3%), keratitis, ocular irritation (1% to 3%), and xerophthalmia. During postmarketing surveillance, central serous chorioretinopathy was reported. Visual impairment may be secondary to the onset of ocular hypertension. Such adverse effects, if they occur, could lead to blindness. Case reports also describe visual impairment, including blurred vision, in patients using topical corticosteroids for eczema of the face. Any patient who develops changes in vision during corticosteroid therapy should be evaluated for ocular hypertension. Consider referral to an ophthalmologist in patients who develop ocular symptoms or who use inhaled or intranasal fluticasone long term. Low potency corticosteroids (e.g., hydrocortisone, dexamethasone) have been reported to be safer for short-term use around the eye area.

Topical preparations of fluticasone may be associated with local adverse effects including acneiform rash, hypertrichosis, maceration of the skin, miliaria, perioral dermatitis, skin atrophy, skin hypopigmentation, striae, and xerosis (7%). A propensity for skin ulcer may develop in patients with markedly impaired circulation and skin atrophy who use topical corticosteroids. Other dermatologic effects with topical application include erythema, skin irritation (2% to 5%), telangiectasia, and vesiculation; these reactions may occur more frequently with the use of occlusive dressings or higher potency corticosteroids. Dermatologic adverse events have also occurred following treatment with inhaled fluticasone. During clinical trials, persons receiving inhaled fluticasone reported symptoms such as contusion, hematoma, laceration, vesicular rash, photodermatitis, dermatosis, eczema, acne vulgaris, ecchymosis or purpura, and burns. Contact dermatitis (1% to 3%), folliculitis (less than 1%), rash (unspecified) (1% to 8%), pruritus (1% to 6%), and urticaria have been reported following the use of both topical and inhaled fluticasone. Use of corticosteroids can lead to impaired wound healing. Fluticasone should not be applied directly or near healing wounds.

Hypersensitivity reactions (e.g., anaphylactoid reactions, angioedema, flushing, wheezing, hypotension, allergic dermatitis, and urticaria) have occurred rarely following treatment with topical and inhaled fluticasone. Fluticasone inhalation powders contain lactose; use of these inhaled fluticasone products in persons with milk protein hypersensitivity has been associated, rarely, with anaphylactoid reactions. Postmarketing reports state that very rare anaphylactic reactions in patients with severe milk allergies have also occurred.

In rare cases, patients on inhaled fluticasone may present with systemic eosinophilic conditions. Some of these patients have clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone. Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. 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.

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.

Headache (1% to 34%) is the most frequently reported nervous system adverse event associated with the use of inhaled and nasal fluticasone therapy. Headache has also been reported with topical use. During clinical trials, persons receiving treatment with inhaled fluticasone also reported experiencing symptoms such as dizziness (1% to 3%), malaise and/or fatigue (16% to 28%), migraine (1% to 3%), and sleep disturbances or insomnia (3% to 13%). Events observed during clinical practice include: agitation, aggression, anxiety, aphonia, depression, muscle paralysis, and restlessness. Also noted, behavioral changes including hyperactivity and irritability were reported very rarely and primarily in children.

Persons receiving treatment with inhaled fluticasone during clinical trial have reported adverse events affecting musculoskeletal system. These adverse reactions included arthralgia and articular rheumatism (17%), back pain (1% to 4%), muscle cramps, muscle inflammation, muscle injury (1% to 2%), muscle spasms, and musculoskeletal pain (1% to 12%).

Adverse events affecting the respiratory tract have been experienced by recipients of fluticasone therapy. The most commonly reported respiratory adverse events included asthma exacerbation (3.35% to 7.2% intranasal and oral inhalation), blood nasal secretions (1% to 3% intranasal), bronchitis (1% to 3% intranasal, 1% to 8% oral inhalation), cough (3.6% to 3.8% intranasal, 1% to 9% oral inhalation, 3% topical), dysphonia (2% to 19% intranasal and oral inhalation), epistaxis (6% to 11.9% intranasal, 1% to 3% oral inhalation), hoarseness (2% to 9% intranasal and oral inhalation), laryngitis (1% to 3% oral inhalation), nasal burning/nasal irritation (2.4% to 3.2% intranasal), nasal congestion (4.4% to 5.6% intranasal, 4% to 22% oral inhalation), nasal excoriation or ulcer (1% intranasal), nasal septal ulceration (6.9% to 7.5% intranasal), pharyngolaryngeal pain (more than 1% intranasal), pharyngitis (1.3% to 7.8% intranasal, 1% to 25% oral inhalation), naso-pharyngitis (1.9% to 7.5% intranasal), rhinitis (1% to 13% intranasal and oral inhalation, less than 1% topical), rhinorrhea (1% to 3% intranasal and oral inhalation), sinusitis (1% to 5% intranasal, 1% to 33% oral inhalation, less than 1% topical), sneezing (1% to 3% oral inhalation), throat irritation (3% to 22% oral inhalation), tonsillitis (1% to 3% oral inhalation), nasal mucosal ulceration (2.5% to 3.8% intranasal), nasal mucosal erythema (5% to 5.6% intranasal), nasal septal erythema (3.8% to 4.3% intranasal), and toothache (1% to 3% intranasal). Other adverse events reported with the use of nasal or inhaled fluticasone included anosmia or loss of smell, bronchospasm, chest tightness, dyspnea, nasal discomfort, nasal dryness, nasal septum perforation, nasal soreness, rhinalgia, and wheezing. If pulmonary symptoms occur during treatment with inhaled fluticasone, health care providers are advised to administer treatment, such as a fast-acting inhaled bronchodilator, to the patient. Epistaxis, nasal erosions, and nasal ulcerations were reported more frequently in patients treated with fluticasone nasal spray than those who received placebo. Nasal septum perforation is a rare, but severe complication of intranasal steroids. Nasal septal perforations were reported in 1 (0.3%) patient treated with fluticasone nasal spray for nasal polyps, compared with none treated with placebo. The patient had a prior history of nasal/sinus surgery. Three (0.3%) patients treated with fluticasone propionate in uncontrolled, open-label trials of 3 to 12 months duration developed nasal septal perforations.

Additional adverse reactions potentially related to fluticasone therapy and occurring more frequently in persons treated with inhaled fluticasone than in persons treated with placebo include changes in appetite, cholecystitis, dental pain (3%), dysmenorrhea (1% to 3%), edema, menstrual irregularity (1% to 3%), oral pain (3%), oral ulceration, otalgia (1% to 3%) palpitations, tooth decay, and weight gain (1% to less than 3%). Adverse reactions occurring with both inhaled and topical fluticasone include fever (1% to 7%) and hyperglycemia. Glycosuria has also been observed in patients being treated with topical fluticasone.

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

Tolerance may occur with the prolonged use of topical and inhaled corticosteroid formulations. This may explain the dramatic responses noted initially by patients early in treatment and an apparent diminished response with time. Tolerance is reversible and may be attenuated by interrupted or cyclic schedules, especially for topical therapy.

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 respective products. Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to fluticasone should not receive any form of fluticasone. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid. Fluticasone inhalation powders (Flovent Diskus, 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 corticosteroids, like fluticasone, has produced reversible hypothalamic-pituitary-adrenal (HPA) suppression, manifestations of Cushing's syndrome, hyperglycemia, and glycosuria in some patients. Use fluticasone with caution in patients with underlying Cushing's syndrome. Conditions which increase systemic absorption of topical corticosteroids include use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), and the use of an occlusive dressing. Patients receiving large doses of a potent topical corticosteroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. Use of intranasal corticosteroids in susceptible individuals or in excess of recommended dosing may result in hypercorticism and adrenal suppression. In the event of such complications, the drug should be slowly discontinued. Although the risk of developing HPA suppression is very low with orally inhaled fluticasone, patients should, nevertheless, be monitored for this possibility. If HPA suppression occurs, 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 inhaled corticosteroids within the last 12 months. Infrequently, signs and symptoms of corticosteroid withdrawal may occur, requiring supplemental systemic corticosteroids. Fluticasone should not be substituted for systemic corticosteroid administration because the amount of inhaled fluticasone that reaches the systemic circulation is insufficient to replace orally administered corticosteroids. Deaths due to adrenal insufficiency have been reported in asthma patients during and following such a transfer.

Topical and inhaled corticosteroids, such as fluticasone, should be used with caution in patients with diabetes mellitus. Exacerbation of diabetes 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. Patients receiving fluticasone nasal sprays should avoid spraying the inhaler directly on the septum (center of the nose).

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 application of topical fluticasone in the presence of infection, including tuberculosis of the skin, active or latent tuberculosis of the respiratory tract, fungal infection, systemic parasitic infection, ocular herpes simplex, and cutaneous or systemic viral infection (e.g., herpes infection, measles, or varicella), 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 respiratory inhaler use should only be done under close medical supervision. Patients using fluticasone nasal sprays 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. A 2-year study of fluticasone (inhalation aerosol 88 or 440 mcg twice daily) in asthma patients found no statistically significant changes in bone mineral density (BMD) via dual-energy x-ray absorptiometry (DEXA) at the lumbar spine. 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. Patients receiving inhaled respiratory 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, postmenopausal status, advanced age, tobacco smoking, malnutrition, and use of other medications that may reduce bone mass. Patients with these risk factors should be monitored and treated with established standards of care. Due to a systemic absorption of less than 2% after appropriate use, adverse effects on bone are not as likely with intranasal fluticasone therapy; however, assess for decrease in bone mineral density initially and periodically thereafter as per standards of care.

Reported clinical experience with fluticasone administered intranasal or via oral respiratory inhalation has not identified differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustments are needed based on geriatric age alone. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that orally inhaled corticosteroids, such as fluticasone, can cause throat irritation and oral candidiasis, particularly if the mouth is not rinsed after administration.

Pharmacokinetic studies have shown that following intranasal and respiratory inhalation administration of fluticasone, most of the drug is absorbed after being swallowed and undergoes extensive first-pass metabolism through the liver. Hepatic impairment may lead to accumulation of fluticasone in plasma. Therefore, patients with hepatic disease should be closely monitored when receiving nasal or orally inhaled fluticasone.

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 be used for brief periods or under close medical supervision in patients with evidence of pre-existing skin atrophy, especially the elderly. Purpura and skin lacerations that may raise the skin and subcutaneous tissue from deep fascia may be more likely to occur with the use of topical corticosteroids in geriatric patients. 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.

Care should be taken to avoid ocular exposure and use of any fluticasone product (topical, nasal, or inhaled) around the eyes as cases of visual impairment and ocular hypertension have been reported with topical and inhaled corticosteroids. Take care during administration not to expose the eyes. Also, glaucoma, increased intraocular pressure, and cataracts have been reported with long-term use of nasal and inhaled corticosteroids. Cataracts and glaucoma have been reported during postmarketing experience with the use of topical corticosteroids. Patients with a change in vision or a history of increased intraocular pressure, glaucoma, or cataracts should be closely monitored during corticosteroid therapy. 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.

The safety and efficacy of orally inhaled fluticasone has not been established for infants and children less than 4 years of age; specific nasal and oral inhalation product labels should be consulted prior to use in children as some products are not FDA-approved for certain populations and/or ages of pediatric patients. The safety and efficacy of intranasal fluticasone furoate (i.e., Flonase Sensimist) has not been established for pediatric patients less than 2 years of age and fluticasone propionate intranasal is not recommended for non-prescription use in children under 4 years of age. The safety and efficacy of intranasal fluticasone propionate (Xhance) has not been established in pediatric patients under the age of 18 years. Growth inhibition has been observed in some children following therapy with high-dose fluticasone propionate inhalations. Children receiving fluticasone respiratory inhalations should be monitored closely for growth inhibition; the effect of fluticasone on final adult height is not known. There is some evidence indicating that intranasal corticosteroids may also cause reduced growth velocity in children. However, data from a 1-year, placebo-controlled trial in children (3 to 9 years of age) with allergic rhinitis receiving fluticasone propionate nasal spray (Flonase) showed no statistically significant adverse effect on growth; no evidence of clinically significant effects on HPA axis function or bone mineral density were observed. Data from a 1-year, placebo-controlled growth study in children (5 years to 8.5 years of age) showed a lower mean growth velocity in the patients receiving fluticasone furoate nasal spray (Veramyst) compared with placebo (mean treatment difference -0.27 cm/year [CI -0.48 to -0.06]). Routine monitoring of growth in children receiving intranasal corticosteroids as well as using the lowest effective dose to minimize systemic effects is recommended. Topical fluticasone preparations are generally not recommended in pediatric patients except where the benefits of treatment would outweigh the potential risks of therapy. Fluticasone ointment (e.g., Cutivate ointment) is recommended only for adult patients; in a study of 35 children with atopic dermatitis treated with fluticasone ointment, subnormal adrenal function was observed with cosyntropin stimulation testing and the FDA has denied approval of this dosage form for use in pediatric patients. Children and infants may absorb proportionally larger amounts of topical corticosteroids due to a larger skin surface area to body weight ratio, and therefore are more susceptible to developing systemic toxicity, especially with high-potency products. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and increased intracranial pressure have been reported in children receiving topical corticosteroid creams and ointments. Adrenal suppression and increased intracranial pressure have also been reported with the use and/or withdrawal of other formulations of corticosteroids in pediatric patients.

There are no randomized clinical studies of fluticasone during pregnancy; there are clinical considerations with the use of fluticasone in pregnant women. Fluticasone should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Infants born to mothers taking substantial corticosteroid doses during pregnancy should be monitored for signs of hypoadrenalism. Available data from published literature on the use of inhaled or intranasal fluticasone propionate in pregnant women have not reported a clear association with adverse developmental outcomes. Fetal abnormalities have been reported in the off-spring of mice, rats, and rabbits exposed to the medications during gestation. Teratogenicity characteristic of corticosteroids, decreased fetal body weight, and skeletal variations was noted in the off-spring of mice, rats, and rabbits exposed to subcutaneous fluticasone at doses less than the maximum recommended human daily inhaled dose (MRHDID) on a mg/m2 basis. When inhaled fluticasone propionate was administered to rats, fetal body weight was decreased, but teratogenicity was not induced at a maternal toxic dose approximately 0.13 times the MRHDID (on a mg/m2 basis with a maternal inhalation dose of 25.7 mcg/kg/day). Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than are humans. Inhaled corticosteroids are often preferred over systemic corticosteroids when use cannot be avoided for the management of asthma during pregnancy. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. Data on the use of medium to high dose inhaled corticosteroid during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. Due to the availability of safety information during pregnancy, budesonide is preferred over other inhaled corticosteroids. However, there are no data to indicate safety concerns with other inhaled corticosteroids, and maintaining a previously established treatment regimen may be more beneficial to the patient. Selection of any pharmacologic treatment for asthma control during pregnancy should include the specific needs of the patient, based on an individual evaluation, and consideration of the potential benefits or risks to the fetus. Similarly, other fluticasone formulations, such as intranasal fluticasone, should be avoided unless the potential therapeutic benefit justifies the added risk to the fetus. Fluorinated topical corticosteroid creams and ointments, like fluticasone, are not recommended for use in pregnancy. Lower potency topical corticosteroids are usually used, if needed.

Fluticasone via inhalation typically results in low systemic concentrations; therefore, the amount excreted into breast-milk after inhalation or nasal use is expected to be very low. Reviewers and an expert panel consider inhaled and oral corticosteroids acceptable to use during breast-feeding. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during lactation. Due to greater availability of data, budesonide is the preferred agent in this population. However, there are no data to indicate safety concerns with other inhaled corticosteroids and maintaining a previously established treatment regimen may be more beneficial to the patient. It is not known whether topical administration of fluticasone could result in sufficient systemic absorption to produce detectable quantities in breast milk. However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast. Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

Patients that apply topical fluticasone to exposed portions of the body should avoid excessive sunlight (UV) exposure from either natural or artificial sources (e.g., tanning booths, sun lamps, etc.).

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


Adults, Adolescents, and Children 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


Adults, Adolescents, and Children 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

Adults, Adolescents, and Children 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 inhalation aerosol; e.g., Flovent HFA):
Adults: 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.
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.
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 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.
Respiratory (Inhalation) dosage (fluticasone propionate inhalation powder; e.g., Flovent Diskus):
Adults : 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.
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.
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.
Respiratory (Inhalation) dosage (fluticasone furoate inhalation powder; i.e., Arnuity Ellipta):
Adults: 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.
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.
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.
Respiratory (Inhalation) dosage (fluticasone propionate inhalation powder; e.g., Armonair Digihaler):
Adults: 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.
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.
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.

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):
Adults: 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.
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.
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.
Respiratory (Inhalation) dosage (fluticasone propionate inhalation powder; e.g., Flovent Diskus):
Adults: 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.
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.
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.
Respiratory (Inhalation) dosage (fluticasone furoate inhalation powder; e.g., Arnuity Ellipta):
Adults: 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.
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):
Adults: 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.
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.
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.

For exercise-induced bronchospasm prophylaxis*:
Oral Inhalation dosage (fluticasone propionate inhalation aerosol suspension; i.e., Flovent HFA):
Adults: 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.
Children and Adolescents 12 years and older: 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.
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.
Oral Inhalation dosage (fluticasone propionate inhalation powder; i.e., Flovent Diskus):
Adults: 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.
Children and Adolescents 12 years and older: 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.
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.
Oral Inhalation dosage (fluticasone furoate inhalation powder; i.e., Arnuity Ellipta):
Adults: 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.
Children and Adolescents 12 years and older: 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.
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.
Oral Inhalation dosage (fluticasone propionate inhalation powder; e.g., Armonair Digihaler):
Adults: 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 and Adolescents 12 years and older: 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 maintenance treatment of chronic obstructive pulmonary disease (COPD)* (e.g., chronic bronchitis* or emphysema*):
Oral Inhalation dosage (fluticasone propionate inhalation powder; i.e., Flovent Diskus):
Adults: Typical doses range from 100 to 250 mcg via oral inhalation twice daily. The optimal dose for COPD is not established, although inhaled corticosteroids (ICS) are well-accepted treatments for patients at risk for exacerbation per COPD guidelines. FDA-approved Max: 2,000 mcg/day. Do not use for the relief of acute bronchospasm; use a short-acting beta-2 agonist (SABA). According to the Global Initiative for Chronic Lung Disease (GOLD) guidelines, ICS may be used in combination with an inhaled long-acting beta-2 agonist (LABA) as initial therapy in group D (those with a high risk of exacerbation). Combination of a LABA with an ICS has the greatest likelihood of reducing exacerbations in patients with blood eosinophil counts of 200 cells/microL or more. An ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD; however clinical trials failed to demonstrate a statistically significant effect on survival. At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a long-acting muscarinic antagonist (LAMA), a LABA, and an inhaled corticosteroid (ICS).
Oral Inhalation dosage (fluticasone furoate inhalation powder; i.e., Arnuity Ellipta):
Adults: A typical fluticasone furoate dose is 100 mcg via oral inhalation once daily. The optimal dose for COPD is not established, although inhaled corticosteroids (ICS) are well-accepted treatments for patients at risk for exacerbation per COPD guidelines. FDA-approved Max: 200 mcg/day. Do not use for the relief of acute bronchospasm; use a short-acting beta-2 agonist (SABA). According to the Global Initiative for Chronic Lung Disease (GOLD) guidelines, ICS may be used in combination with an inhaled long-acting beta-2 agonist (LABA) as initial therapy in group D (those with a high risk of exacerbation). Combination of a LABA with an ICS has the greatest likelihood of reducing exacerbations in patients with blood eosinophil counts of 200 cells/microL or more. An ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD; however clinical trials failed to demonstrate a statistically significant effect on survival. At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a long-acting muscarinic antagonist (LAMA), a LABA, and an inhaled corticosteroid (ICS).

For the treatment of corticosteroid-responsive dermatoses including atopic dermatitis, localized vitiligo, eczema, lichen planus, localized bullous pemphigoid, phimosis, and psoriasis:
-for the general treatment of corticosteroid-responsive dermatoses:
Topical dosage (cream):
Adults: Apply a thin layer topically to the affected skin area(s) 2 times daily. If no improvement within 2 weeks, reassess diagnosis.
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.
Topical dosage (ointment):
Adults: Apply a thin layer topically to the affected skin area(s) 2 times daily. If no improvement within 2 weeks, reassess diagnosis.
-for the treatment of atopic dermatitis:
Topical dosage (cream):
Adults: Apply a thin layer topically to the affected skin area(s) once or twice daily until symptoms resolve. 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.
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):
Adults: 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.
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.
Topical dosage (ointment):
Adults: Apply a thin layer topically to the affected skin area(s) 2 times daily until symptoms resolve. 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):
Adults: Apply a thin layer topically to the affected skin area(s) 2 times daily. If no improvement within 2 weeks, reassess diagnosis. The duration of the therapy depends on factors such as the topical corticosteroid potency, disease severity and anatomic location, and age. After improvement, may consider transitioning to lower-potency corticosteroid, using intermittent therapy, and combining treatment with noncorticosteroidal agents. Taper by reducing use to every other day, then twice weekly, then discontinue if adequate control is maintained. Guidelines recommend class 1 to 5 topical corticosteroids for up to 4 weeks for plaque psoriasis not involving intertriginous areas and class 1 to 7 topical corticosteroids for a minimum of up to 4 weeks for scalp psoriasis. Use of topical corticosteroids for more than 12 weeks may be considered under careful supervision.
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.
Topical dosage (ointment):
Adults: Apply a thin film topically to the affected skin area(s) 2 times daily. The duration of the therapy depends on factors such as the topical corticosteroid potency, disease severity and anatomic location, and age. After improvement, may consider transitioning to lower-potency corticosteroid, using intermittent therapy, and combining treatment with noncorticosteroidal agents. Taper by reducing use to every other day, then twice weekly, then discontinue if adequate control is maintained. Guidelines recommend class 1 to 5 topical corticosteroids for up to 4 weeks for plaque psoriasis not involving intertriginous areas and class 1 to 7 topical corticosteroids for a minimum of up to 4 weeks for scalp psoriasis. Use of topical corticosteroids for more than 12 weeks may be considered under careful supervision.

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; e.g., OTC Flonase Sensimist):
Adults: 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.
Children and Adolescents 12 years and older: 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.
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.
Nasal dosage (fluticasone propionate 50 mcg/spray; e.g., OTC Flonase Allergy Relief):
Adults: 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.
Children and Adolescents 12 years and older: 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.
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.

For the management of nasal symptoms associated with vasomotor rhinitis (perennial nonallergic rhinitis):
Nasal dosage (fluticasone propionate 50 mcg/spray nasal spray; Rx-only):
Adults: 2 sprays per nostril once daily (200 mcg/day). May also administer as 1 spray per nostril twice 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).
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 chronic rhinosinusitis with nasal polyps (CRSwNP):
Nasal inhalation dosage ( fluticasone propionate nasal spray 93 mcg/spray; i.e., Xhance):
Adults: 1 spray (93 mcg of fluticasone propionate per spray) in each nostril twice daily (total daily dose, 372 mcg/day). A dose of 2 sprays in each nostril twice daily may also be effective in some patients. Max: 2 sprays in each nostril twice daily (total daily dose, 744 mcg/day). Effectiveness depends on regular use; patient should use at regular intervals. Individual patients will experience a variable time to onset and different degrees of symptom relief.

Maximum Dosage Limits:
In general, corticosteroid dosage must be individualized and is highly variable depending on the nature and severity of the disease, route and product of administration, and on patient age and response. For some products maximum dosage limits have not been specified.
-Adults
Topical: Twice daily application for cream/ointment; once daily application for lotion.
Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy); 744 mcg/day intranasally for fluticasone propionate for nasal polyps (Xhance).
Inhaler maximum dosages: 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 (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).
-Geriatric
Topical: Twice daily application for cream/ointment; once daily application for lotion.
Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy); 744 mcg/day intranasally for fluticasone propionate for nasal polyps (Xhance).
Inhaler maximum dosages: 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 (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).
-Adolescents
Topical: Twice daily application for cream/ointment; once daily application for lotion.
Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance).
Inhaler maximum dosages: 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 (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).
-Children
12 years:
Topical: Twice daily application for cream/ointment; once daily application for lotion.
Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance).
Inhaler maximum dosages: 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 (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).

5 to 11 years:
Topical: Twice daily application for cream/ointment; once daily application for lotion.
Intranasal: 55 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance).
Inhaler maximum dosages: 200 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus), however doses of up to 400 mcg/day off-label have been used for asthma; 176 mcg/day via fluticasone propionate MDI (Flovent HFA) per FDA-approved labeling, however, doses of 352 mcg/day or more have been used off-label for asthma; 50 mcg/day via fluticasone furoate DPI (Arnuity Ellipta); 110 mcg/day via fluticasone propionate DPI (Armonair Digihaler).

4 years:
Topical: Twice daily application for cream; once daily application for lotion.
Intranasal: 55 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance).
Inhaler maximum dosages: 200 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus); 176 mcg/day via fluticasone propionate MDI (Flovent HFA) per FDA-approved labeling, however, doses of 352 mcg/day or more have been used off-label for asthma; 110 mcg/day via fluticasone propionate DPI (Armonair Digihaler). Safety and efficacy of fluticasone furoate DPI (Arnuity Ellipta) have not been established.

2 to 3 years: Twice daily application for cream; once daily application for lotion; 55 mcg/day intranasally for fluticasone furoate (Flonase Sensimist). Fluticasone propionate MDI (Flovent HFA) has been used off-label in treatment of asthma. Safety and efficacy have not been established for other formulations.

1 year: Twice daily application for cream; once daily application for lotion. Fluticasone propionate MDI (Flovent HFA) has been used off-label in treatment of asthma. Safety and efficacy have not been established for other formulations.
-Infants
3 months and older: Twice daily application for cream; once daily application for lotion. Safety and efficacy have not been established for other formulations.
1 to 2 months: Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; however, caution is recommended in those with moderate or severe hepatic impairment. Patients with hepatic disease who are receiving fluticasone propionate for nasal polyps should be closely monitored.

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

Abatacept: (Moderate) Concomitant use of immunosuppressives, as well as long-term corticosteroids, may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Acetaminophen; Aspirin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Acetaminophen; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Acetazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.

Adagrasib: (Major) Coadministration of inhaled fluticasone propionate and adagrasib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Aldesleukin, IL-2: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Alemtuzumab: (Moderate) Concomitant use of alemtuzumab with immunosuppressant doses of corticosteroids may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.

Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Alpha-glucosidase Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Amifampridine: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.

Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Aminolevulinic Acid: (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment.

Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Amphotericin B lipid complex (ABLC): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.

Amphotericin B liposomal (LAmB): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.

Amphotericin B: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.

Antithymocyte Globulin: (Moderate) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Arsenic Trioxide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.

Articaine; Epinephrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.

Asparaginase Erwinia chrysanthemi: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.

Aspirin, ASA: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Butalbital; Caffeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Caffeine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Dipyridamole: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Omeprazole: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Aspirin, ASA; Oxycodone: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Atazanavir: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Atazanavir; Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Atenolol; Chlorthalidone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Atracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.

Azathioprine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Azilsartan; Chlorthalidone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Basiliximab: (Minor) Because systemically administered corticosteroids have immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives.

Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Bexagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Bismuth Subsalicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Bortezomib: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Brompheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Bupivacaine; Epinephrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.

Bupropion: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.

Bupropion; Naltrexone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.

Butalbital; Acetaminophen: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.

Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.

Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.

Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use. (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Caffeine; Sodium Benzoate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.

Canagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Carbamazepine: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.

Carmustine, BCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Ceritinib: (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Chlorambucil: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Chloramphenicol: (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Chlorothiazide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Chlorpropamide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Chlorthalidone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Chlorthalidone; Clonidine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Cisatracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.

Clarithromycin: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Clofarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Codeine; Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Dapagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Darunavir: (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Darunavir; Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.

Delavirdine: (Major) Coadministration of inhaled fluticasone propionate and delavirdine is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection.

Desmopressin: (Major) Desmopressin is contraindicated with concomitant inhaled or systemic corticosteroid use due to an increased risk of hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.

Dextromethorphan; Bupropion: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk.

Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Dofetilide: (Major) Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia, predisposing patients to interactions with certain other medications. Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide.

Droperidol: (Moderate) Caution is advised when using droperidol in combination with corticosteroids which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.

Dulaglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Echinacea: (Moderate) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to immunosuppressant drugs like corticosteroids. For some patients who are using corticosteroids for serious illness, such as cancer or organ transplant, this potential interaction may result in the preferable avoidance of Echinacea. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.

Econazole: (Minor) In vitro studies indicate that corticosteroids inhibit the antifungal activity of econazole against C. albicans in a concentration-dependent manner. When the concentration of the corticosteroid was equal to or greater than that of econazole on a weight basis, the antifungal activity of econazole was substantially inhibited. When the corticosteroid concentration was one-tenth that of econazole, no inhibition of antifungal activity was observed.

Elbasvir; Grazoprevir: (Moderate) Administering fluticasone with elbasvir; grazoprevir may result in elevated fluticasone plasma concentrations. Fluticasone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.

Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Empagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Ephedrine: (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage.

Ephedrine; Guaifenesin: (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage.

Epinephrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.

Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Ertugliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Estramustine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Estrogens: (Moderate) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect.

Exenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Fosamprenavir: (Major) Coadministration of inhaled fluticasone propionate and fosamprenavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Fosphenytoin: (Moderate) Monitor for decreased corticosteroid efficacy if fluticasone is used with fosphenytoin; a dosage increase may be necessary. Concurrent use may decrease the exposure of fluticasone.

Glimepiride: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Glipizide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Glyburide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Glycerol Phenylbutyrate: (Moderate) Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely.

Grapefruit juice: (Major) Instruct patients using inhaled fluticasone propionate products to avoid grapefruit juice. Patients using fluticasone furoate products should be aware of the potential for increased adverse effects if they regularly consume grapefruit juice. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; grapefruit juice is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with haloperidol.

Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin.

Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Hydroxyurea: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.

Ibritumomab Tiuxetan: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Idelalisib: (Major) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Indapamide: (Moderate) Additive hypokalemia may occur when indapamide is coadministered with other drugs with a significant risk of hypokalemia such as systemic corticosteroids. Coadminister with caution and careful monitoring.

Indinavir: (Major) Coadministration of inhaled fluticasone propionate and indinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Inebilizumab: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab.

Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Insulins: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Interferon Alfa-2b: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Isoproterenol: (Moderate) The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05 to 2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death.

Isotretinoin: (Minor) Both isotretinoin and corticosteroids can cause osteoporosis during chronic use. Patients receiving systemic corticosteroids should receive isotretinoin therapy with caution.

Itraconazole: (Major) Coadministration of inhaled fluticasone propionate and itraconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Ketoconazole: (Major) Coadministration of inhaled fluticasone propionate and ketoconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ketoconazole increased plasma fluticasone exposure by 1.9-fold with a 45% decrease in plasma cortisol AUC, but had no effect on urinary excretion of cortisol. Ketoconazole increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of fluticasone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Concurrent use of all 3 drugs together is not recommended because increased systemic corticosteroid adverse events may develop. Fluticasone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. In a drug interaction study, use of fluticasone with another strong CYP3A4 inhibitor resulted in a 1.9-fold increase in plasma fluticasone exposure and a 45% decrease in plasma cortisol exposure, but had no effect on urinary excretion of cortisol.

Levoketoconazole: (Major) Coadministration of inhaled fluticasone propionate and ketoconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ketoconazole increased plasma fluticasone exposure by 1.9-fold with a 45% decrease in plasma cortisol AUC, but had no effect on urinary excretion of cortisol. Ketoconazole increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Lidocaine; Epinephrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.

Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Liraglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Lixisenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Lomustine, CCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Lonafarnib: (Major) Coadministration of inhaled fluticasone propionate and lonafarnib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Lonapegsomatropin: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted.

Loop diuretics: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.

Lopinavir; Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as corticosteroids. Healthcare providers are advised to discontinue corticosteroid therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.

Magnesium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Mannitol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.

Mecasermin, Recombinant, rh-IGF-1: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.

Meglitinides: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Metformin; Repaglinide: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Methazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with methazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. The chronic use of corticosteroids may augment calcium excretion with methazolamide leading to increased risk for hypocalcemia and/or osteoporosis.

Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.

Methenamine; Sodium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Methoxsalen: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Metolazone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Metyrapone: (Major) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of topical corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.

Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia.

Mifepristone: (Major) Mifepristone for termination of pregnancy is contraindicated in patients on long-term corticosteroid therapy and mifepristone for Cushing's disease or other chronic conditions is contraindicated in patients who require concomitant treatment with systemic corticosteroids for life-saving purposes, such as serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). For other situations where corticosteroids are used for treating non-life threatening conditions, mifepristone may lead to reduced corticosteroid efficacy and exacerbation or deterioration of such conditions. This is because mifepristone exhibits antiglucocorticoid activity that may antagonize corticosteroid therapy and the stabilization of the underlying corticosteroid-treated illness. Mifepristone may also cause adrenal insufficiency, so patients receiving corticosteroids for non life-threatening illness require close monitoring. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, If adrenal insufficiency occurs, stop mifepristone treatment and administer systemic glucocorticoids without delay; high doses may be needed to treat these events. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours).

Mitotane: (Moderate) Use caution if mitotane and fluticasone are used concomitantly, and monitor for decreased efficacy of fluticasone and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and fluticasone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of fluticasone.

Mitoxantrone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Natalizumab: (Major) Ordinarily, patients receiving chronic immunosuppressant therapy should not be treated with natalizumab. Treatment recommendations for combined corticosteroid therapy are dependent on the underlying indication for natalizumab therapy. Corticosteroids should be tapered in those patients with Crohn's disease who are on chronic corticosteroids when they start natalizumab therapy, as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within 6 months, discontinue natalizumab. The concomitant use of natalizumab and corticosteroids may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy, over the risk observed with use of natalizumab alone. In multiple sclerosis (MS) clinical trials, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in natalizumab-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. Short courses of steroid use during natalizumab, such as when they are needed for MS relapse treatment, appear to be acceptable for use concurrently.

Nateglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Nefazodone: (Major) Coadministration of inhaled fluticasone propionate and nefazodone is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Nelarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Nelfinavir: (Major) Coadministration of inhaled fluticasone propionate and nelfinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Neostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as neostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating systemic corticosteroid therapy.

Neostigmine; Glycopyrrolate: (Moderate) Concomitant use of anticholinesterase agents, such as neostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating systemic corticosteroid therapy.

Neuromuscular blockers: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.

Nirmatrelvir; Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.

Ofatumumab: (Moderate) Concomitant use of ofatumumab with corticosteroids may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. Ofatumumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids.

Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy.

Pancuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.

Pegaspargase: (Moderate) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids.

Penicillamine: (Major) Agents such as immunosuppressives have adverse reactions similar to those of penicillamine. Concomitant use of penicillamine with these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity.

Phenobarbital: (Moderate) Coadministration may result in decreased exposure to fluticasone. Phenobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.

Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Phenobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.

Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Phenytoin: (Moderate) Monitor for decreased corticosteroid efficacy if fluticasone is used with phenytoin; a dosage increase may be necessary. Concurrent use may decrease the exposure of fluticasone.

Photosensitizing agents (topical): (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment.

Physostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy.

Pimozide: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.

Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Posaconazole: (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.

Potassium-sparing diuretics: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.

Pramlintide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.

Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.

Prilocaine; Epinephrine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.

Primidone: (Moderate) Coadministration may result in decreased exposure to fluticasone. Primidone is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.

Promethazine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.

Propranolol: (Moderate) Monitor blood sugar during concomitant corticosteroid and propranolol use due to risk for hypoglycemia. Concurrent use may increase risk of hypoglycemia because of loss of the counter-regulatory cortisol response.

Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.

Pyridostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as pyridostigmine, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Ribociclib: (Major) Coadministration of inhaled fluticasone propionate and ribociclib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Ribociclib; Letrozole: (Major) Coadministration of inhaled fluticasone propionate and ribociclib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Rituximab: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.

Rituximab; Hyaluronidase: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.

Rocuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.

Salicylates: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Salsalate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Saquinavir: (Major) Coadministration of inhaled fluticasone propionate and saquinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; saquinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Sargramostim, GM-CSF: (Major) Avoid the concomitant use of sargramostim and systemic corticosteroid agents due to the risk of additive myeloproliferative effects. If coadministration of these drugs is required, frequently monitor patients for clinical and laboratory signs of excess myeloproliferative effects (e.g., leukocytosis). Sargramostim is a recombinant human granulocyte-macrophage colony-stimulating factor that works by promoting proliferation and differentiation of hematopoietic progenitor cells.

Semaglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Sodium Benzoate; Sodium Phenylacetate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.

Sodium Phenylbutyrate: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids.

Sodium Phenylbutyrate; Taurursodiol: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids.

Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.

Somapacitan: (Moderate) Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress steroid doses following initiation of somapacitan. Monitor for signs/symptoms of reduced serum cortisol concentrations. Growth hormone (GH) inhibits 11betaHSD-1. Consequently, patients with untreated GH deficiency have relative increases in 11betaHSD-1 and serum cortisol. The initiation of somapacitan may result in inhibition of 11betaHSD-1 and reduced serum cortisol concentrations.

Somatrogon: (Moderate) Monitor for a decrease in serum cortisol concentrations and corticosteroid efficacy during concurrent use of corticosteroids and somatrogon. Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress steroid doses following initiation of somatrogon. Additionally, supraphysiologic glucocorticoid treatment may attenuate the growth promoting effects of somatrogon. Carefully adjust glucocorticoid replacement dosing to avoid hypoadrenalism and an inhibitory effect on growth.

Somatropin, rh-GH: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted.

Sotagliflozin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Succinylcholine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.

Sulfonylureas: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Testosterone: (Moderate) Monitor for fluid retention during concurrent corticosteroid and testosterone use. Concurrent use may result in increased fluid retention.

Thiazide diuretics: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Thiazolidinediones: (Moderate) Monitor blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Tipranavir: (Major) Coadministration of inhaled fluticasone propionate and tipranavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Tirzepatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.

Tretinoin, ATRA: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.

Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

Tucatinib: (Major) Coadministration of inhaled fluticasone propionate and tucatinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss.

Vecuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years.

Vigabatrin: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.

Vincristine Liposomal: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.

Vonoprazan; Amoxicillin; Clarithromycin: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.

Voriconazole: (Moderate) Monitor for potential adrenal dysfunction with concomitant use of voriconazole and fluticasone. In patients taking corticosteroids, voriconazole-associated CYP3A4 inhibition of their metabolism may lead to corticosteroid excess and adrenal suppression. Corticosteroid exposure is likely to be increased. Concomitant administration of another strong CYP3A4 inhibitor increased plasma fluticasone propionate exposure resulting in a 45% to 86% decrease in serum cortisol AUC and increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol. Voriconazole is a strong CYP3A4 inhibitor, and fluticasone is a CYP3A4 substrate.

Vorinostat: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.

Warfarin: (Moderate) Monitor the INR if warfarin is administered with corticosteroids. The effect of corticosteroids on warfarin is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids; however, limited published data exist, and the mechanism of the interaction is not well described. High-dose corticosteroids appear to pose a greater risk for increased anticoagulant effect. In addition, corticosteroids have been associated with a risk of peptic ulcer and gastrointestinal bleeding.

Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids.

Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme which 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.

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 as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. 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. Since 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 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 currently unknown.

In the treatment of nasal polyps, the precise mechanism through which intranasal fluticasone propionate affects nasal polyps and associated inflammatory symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. The anti-inflammatory action of corticosteroids contributes to their efficacy. In 7 trials in adults, fluticasone propionate nasal spray decreased nasal mucosal eosinophils in 66% of patients (35% for placebo) and basophils in 39% of patients (28% for placebo). In addition, studies suggest that carbon dioxide, which is present in the exhaled breath delivered into the nose through the device, may influence inflammatory mediator activity and neuropeptide activity, possibly through mechanisms of action that also include removal of nitric oxide, change in pH, or positive pressure. The direct relationship of these findings to long-term symptom relief is not known.

Fluticasone is administered by oral respiratory 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. The only circulating metabolite of fluticasone detected in man is the 17beta-carboxylic acid derivative, which is formed through the CYP3A4 pathway; this metabolite has negligible pharmacologic activity. 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 is approximately 7.8 hours; the half-life of intravenous fluticasone furoate averages 15 hours while half-life after oral inhalation averages 11.2 to 24 hours.

Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4
The potential for fluticasone to inhibit or induce metabolic enzymes and transporter systems is negligible at low respiratory inhalation doses. However, fluticasone is a substrate of CYP3A4, and systemic exposure after oral inhalational use 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. 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. When 25 grams of 0.0005% 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. In a rat model, 80% of radiolabeled 0.05% fluticasone propionate cream or ointment (1 g/kg over 24 hours) was recovered at the end of 7 days; 73% was found at the application site surface, less than 1% was in the skin, and approximately 5% was absorbed systemically. Skin absorption continued for the length of the trial, indicating long retention time at the application site.

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 patients 12 years and older; data 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%.

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 Digihaler)
Oral systemic bioavailability of fluticasone propionate is negligible (approximately 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. Peak plasma concentrations are obtained 1 hour after administration.

Other Route(s)
Intranasal Route
Fluticasone furoate nasal spray (e.g., Flonase Sensimist)
The average absolute bioavailability of intranasal fluticasone fluticasone furoate is less than 0.5%. 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.

Fluticasone propionate nasal spray (e.g., Flonase)
The average absolute bioavailability of intranasal fluticasone propionate is less than 2%.

Fluticasone propionate nasal spray (e.g., Xhance)
Due to the low bioavailability by the intranasal route, the majority of the pharmacokinetic data were obtained via other routes of administration. Local exposure within the nasal cavity with this product will differ when used without exhalation through the device. The mean (SD) peak exposure (Cmax) and total exposure (AUC) following administration of fluticasone propionate 186 mcg during exhalation were 17.2 +/- 7.40 pg/mL and 111.7 +/- 49.75 pg x hours/mL, respectively, and were 25.3 +/- 10.34 pg/mL and 171.7 +/- 85.55 pg x hours/mL, respectively, following a dose of fluticasone propionate 372 mcg in healthy subjects. The Cmax and AUC following a dose of fluticasone propionate 372 mcg in patients with mild to moderate asthma were 28.7 +/- 18.72 pg/mL and 222.6 +/- 84.60 pg x hours/mL, respectively.


-Special Populations
Hepatic Impairment
Since fluticasone is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma when the drug is given intranasally or via oral respiratory inhalation. Pharmacokinetics of fluticasone may be altered in patients with hepatic impairment, as evidenced by increases in fluticasone AUC and reductions of serum cortisol. A study of a single 400 mcg dose of orally inhaled fluticasone furoate in patients with moderate hepatic impairment (Child-Pugh Class B) resulted in an increased Cmax (42%) and AUC (172%). This increased exposure resulted in an approximately 20% reduction in serum cortisol concentrations. 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 ethnic groups. No significant difference in clearance of fluticasone propionate in Caucasian, African-American, Asian, or Hispanic populations has been observed.