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Fluticasone (Oral Inhalation)

Pronunciation

Pronunciation

(floo TIK a sone)

Index Terms

  • Flovent
  • Fluticasone Furoate
  • Fluticasone Propionate

Dosage Forms

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

Aerosol, Inhalation, as propionate:

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

Aerosol Powder Breath Activated, Inhalation, as furoate:

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

Aerosol Powder Breath Activated, Inhalation, as propionate:

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

Brand Names: U.S.

  • Arnuity Ellipta
  • Flovent Diskus
  • Flovent HFA

Pharmacologic Category

  • Corticosteroid, Inhalant (Oral)

Pharmacology

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

Absorption

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

Distribution

4.2 L/kg

Metabolism

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

Excretion

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

Onset of Action

Maximal benefit may take 1 to 2 weeks or longer

Time to Peak

0.5 to 1 hour

Half-Life Elimination

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

Protein Binding

>99%

Special Populations: Hepatic Function Impairment

Accumulation of fluticasone in plasma may occur.

Use: Labeled Indications

Asthma:

Arnuity Ellipta: Maintenance treatment of asthma as prophylactic therapy in patients 12 years and older

Flovent Diskus and Flovent HFA: Maintenance treatment of asthma as prophylactic therapy in patients 4 years and older; for patients requiring oral corticosteroid therapy for asthma to assist in total discontinuation or reduction of total oral dose

Limitations of use: Not indicated for relief of acute bronchospasm

Guideline recommendations: A low-dose inhaled corticosteroid (in addition to an as-needed short acting beta2-agonist) is the initial preferred long term control medication for children, adolescents, and adult patients with persistent asthma who are candidates for treatment according to a step-wise treatment approach (GINA 2016; NAEPP 2007).

Contraindications

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

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

Canadian labeling: Additional contraindications (not in US labeling): Flovent HFA and Flovent Diskus: Moderate to severe bronchiectasis; untreated fungal, bacterial or tubercular infections of the respiratory tract

Dosing: Adult

Asthma: Inhalation, oral: Note: Titrate to the lowest effective dose once asthma stability is achieved

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

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

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

Flovent HFA (fluticasone propionate):

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

Bronchodilator alone: Initial: 88 mcg twice daily; maximum: 440 mcg twice daily

Inhaled corticosteroids: Initial: 88 to 220 mcg twice daily (initial dose >88 mcg twice daily may be considered in patients previously requiring higher doses of inhaled corticosteroids); maximum: 440 mcg twice daily

Oral corticosteroids (OCS): Initial: 440 mcg twice daily; maximum: 880 mcg twice daily.

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

Mild asthma: 100 to 250 mcg twice daily

Moderate asthma: 250 to 500 mcg twice daily

Severe asthma: 500 mcg twice daily; may increase up to 1000 mcg twice daily in very severe patients (eg, patients using oral corticosteroids [OCS])

Asthma guidelines:

National Asthma Education and Prevention Program guidelines (NAEPP 2007): HFA inhaler (refers to Flovent HFA 44 mcg, 110 mcg, and 220 mcg strengths available in US): Note: Administer in divided doses twice daily.

“Low” dose: 88 to 264 mcg/day

“Medium” dose: >264 to 440 mcg/day

“High” dose: >440 mcg/day

Global Initiative for Asthma guidelines (GINA 2016): HFA inhaler (refers to Flovent HFA 50 mcg, 125 mcg, and 250 mcg strengths available in Canada):

“Low” dose: 100 to 250 mcg daily

“Medium” dose: >250 to 500 mcg daily

“High” dose: >500 mcg daily

Flovent Diskus (fluticasone propionate):

US labeling: Note: May increase dose after 2 weeks of therapy in patients who are not adequately controlled.

Dosing based on previous asthma therapy:

Bronchodilator alone: Initial: 100 mcg twice daily; maximum: 500 mcg twice daily

Inhaled corticosteroids: Initial: 100 to 250 mcg twice daily; maximum: 500 mcg twice daily; initial dose >100 mcg twice daily may be considered in patients with poorer asthma control or those previously requiring high ranges of inhaled corticosteroids

Oral corticosteroids (OCS): Initial: 500 to 1000 mcg twice daily; maximum: 1000 mcg twice daily

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

Mild asthma: 100 to 250 mcg twice daily

Moderate asthma: 250 to 500 mcg twice daily

Severe asthma: 500 mcg twice daily; may increase up to 1000 mcg twice daily in very severe patients (eg, patients using oral corticosteroids [OCS])

Asthma guidelines:

National Asthma Education and Prevention Program guidelines (NAEPP 2007): Dry powder inhaler (refers to Flovent Diskus 50 mcg, 100 mcg, and 250 mcg strengths available in the US and Canada, and the 500 mcg strength available in Canada): Note: Administer in divided doses twice daily:

“Low” dose: 100 to 300 mcg/day

“Medium” dose: >300 to 500 mcg/day

“High” dose: >500 mcg/day

Global Initiative for Asthma guidelines (GINA 2016): Dry powder inhaler (refers to Flovent Diskus 50 mcg, 100 mcg, and 250 mcg strengths available in the US and Canada, and the 500 mcg strength available in Canada)

“Low” dose: 100 to 250 mcg daily

“Medium” dose: >250 to 500 mcg daily

“High” dose: >500 mcg daily

Conversion: Conversion from oral systemic corticosteroids to orally inhaled corticosteroids: When converting from oral corticosteroids (OCS) to orally inhaled corticosteroids, initiate oral inhalation therapy in patients whose asthma is previously stabilized on OCS. Gradual OCS dose reductions should begin ~7 days after starting inhaled therapy. Flovent Diskus and Flovent HFA US labeling recommend reducing prednisone dose no more rapidly than 2.5 to 5 mg/day (or equivalent of other OCS) weekly. Flovent Diskus and Flovent HFA Canadian labeling recommend decreasing the daily dose of prednisone by 1 mg (or equivalent of other OCS) no more rapidly than weekly in adults who are closely monitored or every 10 days if not closely monitored. Arnuity Ellipta Canadian labeling recommends decreasing the daily prednisone dose by 2.5 mg (or equivalent of other OCS) no more rapidly than weekly. If adrenal insufficiency occurs, resume OCS therapy; initiate a more gradual withdrawal. When transitioning from systemic to inhaled corticosteroids, supplemental systemic corticosteroid therapy may be necessary during periods of stress or during severe asthma attacks.

Chronic obstructive pulmonary disease (stable) (off-label use): Inhalation, oral: 50 to 500 mcg/day in combination with a long-acting bronchodilator (GOLD 2014)

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Asthma: Inhalation, oral: Note: Titrate to lowest effective dose once asthma stability achieved.

Arnuity Ellipta (fluticasone furoate): Children ≥12 years and Adolescents: Refer to adult dosing.

Flovent HFA (fluticasone propionate):

US labeling:

Children 4 to 11 years: Initial: 88 mcg twice daily; maximum: 88 mcg twice daily

Children ≥12 years and Adolescents: Refer to adult dosing.

Canadian labeling:

Children 1 to 3 years: 100 mcg twice daily

Children 4 to 15 years: 100 mcg twice daily. Note: Canadian labeling recommends Flovent HFA be administered as a minimum of 2 inhalations twice daily; therefore, patients requiring lower or higher dosages than 100 mcg twice daily should use Flovent Diskus.

Adolescents ≥16 years and Adults: Refer to adult dosing.

Asthma guidelines:

National Asthma Education and Prevention Program guidelines (NAEPP 2007): HFA inhaler (refers to Flovent HFA 44 mcg, 110 mcg, and 220 mcg strengths available in US) Note: Administer in divided doses twice daily

“Low” dose:

0 to 4 years: 176 mcg/day

5 to 11 years: 88 to 176 mcg/day

≥12 years: 88 to 264 mcg/day

“Medium” dose:

0 to 4 years: >176 to 352 mcg/day

5 to 11 years: >176 to 352 mcg/day

≥12 years: >264 to 440 mcg/day

“High” dose:

0 to 4 years: >352 mcg/day

5 to 11 years: >352 mcg/day

≥12 years: >440 mcg/day

Global Initiative for Asthma guidelines (GINA 2016): HFA inhaler (refers to Flovent HFA 50 mcg, 125 mcg, and 250 mcg strengths available in Canada):

Children ≤5 years: “Low” dose: 100 mcg daily

Children 6 to 11 years:

“Low” dose: 100 to 200 mcg daily

“Medium” dose: >200 to 500 mcg daily

“High” dose: >500 mcg daily

Children ≥12 years and Adolescents: Refer to adult dosing.

Flovent Diskus (fluticasone propionate):

US labeling:

Children 4 to 11 years: Initial: 50 mcg twice daily; may increase to maximum dose of 100 mcg twice daily in patients not adequately controlled after 2 weeks of therapy. Initial dose >50 mcg twice daily may be considered in patients with poorer asthma control or those previously requiring high ranges of inhaled corticosteroids.

Adolescents: Refer to adult dosing.

Canadian labeling:

Children 4 to 16 years: Initial: 50 to 100 mcg twice daily; may increase up to 200 mcg twice daily after ~1 week of therapy in patients not adequately controlled

Adolescents ≥16 years: Refer to adult dosing.

Asthma guidelines:

National Asthma Education and Prevention Program guidelines (NAEPP 2007): (administer in divided doses twice daily): Dry powder inhaler (refers to Flovent Diskus 50 mcg, 100 mcg, and 250 mcg strengths available in the US and Canada, and the 500 mcg strength available in Canada)

“Low” dose:

5 to 11 years: 100 to 200 mcg/day

≥12 years: 100 to 300 mcg/day

“Medium” dose:

5 to 11 years: >200 to 400 mcg/day

≥12 years: >300 to 500 mcg/day

“High” dose:

5 to 11 years: >400 mcg/day

≥12 years: >500 mcg/day

Global Initiative for Asthma guidelines (GINA 2016): Dry powder inhaler (refers to Flovent Diskus 50 mcg, 100 mcg, and 250 mcg strengths available in US and Canada, and the 500 mcg strength available in Canada)

Children 6 to 11 years:

“Low” dose: 100 to 200 mcg daily

“Medium” dose: >200 to 400 mcg daily

“High” dose: >400 mcg daily

Children ≥12 years and Adolescents: Refer to adult dosing.

Conversion: Conversion from oral systemic corticosteroids to orally inhaled corticosteroids: When converting from oral corticosteroids (OCS) to orally inhaled corticosteroids, initiate oral inhalation therapy in patients whose asthma is previously stabilized on OCS. Gradual OCS dose reductions should begin ~7 days after starting inhaled therapy. Flovent Diskus and Flovent HFA US labeling recommend reducing prednisone dose no more rapidly than 2.5 to 5 mg/day (or equivalent of other OCS) weekly in children ≥12 years but does not provide a recommendation for children <12 years. A similar approach to OCS dose reduction would however seem advisable. Flovent Diskus and Flovent HFA Canadian labeling recommend decreasing the daily dose of prednisone by 1 mg (or equivalent of other OCS) every 8 days in children who are closely monitored or every 20 days if not closely monitored. Arnuity Ellipta Canadian labeling recommends decreasing the daily prednisone dose by 2.5 mg (or equivalent of other OCS) no more rapidly than weekly. If adrenal insufficiency occurs, resume OCS therapy; initiate a more gradual withdrawal. When transitioning from systemic to inhaled corticosteroids, supplemental systemic corticosteroid therapy may be necessary during periods of stress or during severe asthma attacks.

Eosinophilic esophagitis (off-label use): Oral (off-label route):

Children ≥2 years and Adolescents: 176 to 880 mcg/day of aerosolized fluticasone swallowed (not inhaled). Dose may be divided into 2 doses (Konikoff 2006; Teitelbaum 2002). Doses as high as 880 mcg twice daily have been reported (Butz 2014). Alternatively, may dose according to age:

Children 2 to 4 years: 88 mcg of aerosolized fluticasone swallowed (not inhaled) twice daily (176 mcg/day) (Teitelbaum 2002)

Children 5 to 10 years: 220 mcg of aerosolized fluticasone swallowed (not inhaled) twice daily (440 mcg/day) (Teitelbaum 2002)

Children ≥11 years and Adolescents:440 mcg of aerosolized fluticasone swallowed (not inhaled) twice daily (880 mcg/day) (Teitelbaum 2002)

Dosing: Renal Impairment

Arnuity Ellipta: No dosage adjustment necessary.

Flovent Diskus and Flovent HFA:

US labeling: There are no dosage adjustment provided in the manufacturer's labeling (has not been studied).

Canadian labeling: No dosage adjustment necessary.

Dosing: Hepatic Impairment

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

Canadian labeling:

Arnuity Ellipta:

Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Moderate or severe impairment (Child-Pugh class B or C): Maximum dose: 100 mcg daily

Flovent HFA and Flovent Diskus: No dosage adjustment necessary.

Administration

Inhalation, oral: Aerosol inhalation: Flovent HFA: Shake container thoroughly before using. Take 3-5 deep breaths. Use inhaler on inspiration. Allow 1 full minute between inhalations. Rinse mouth with water after use to reduce aftertaste and incidence of candidiasis; do not swallow. Inhaler must be primed before first use, when not used for 7 days, or if dropped. To prime the first time, release 4 sprays into air; shake well before each spray and spray away from face. If dropped or not used for 7 days, prime by releasing a single test spray. Patient should contact pharmacy for refill when the dose counter reads “020”. Discard device when the dose counter reads “000”. Do not use “float” test to determine contents.

Powder for oral inhalation:

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

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

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

Dietary Considerations

Arnuity Ellipta and Flovent Diskus contains lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Storage

Arnuity Ellipta:

US labeling: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F). Store in a dry place away from direct heat or sunlight. Discard after 6 weeks from removal from protective foil pouch or when the dose counter reads “0” (whichever comes first); device is not reusable.

Canadian labeling: Store at ≤25°C (77°F). If stored in a refrigerator, allow to warm to room temperature for at least 1 hour prior to use. Discard after 6 weeks from removal from protective foil pouch or when the dose counter reads “0” (whichever comes first); device is not reusable.

Flovent Diskus: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F). Store in a dry place away from direct heat or sunlight. Discard after 6 weeks (50 mcg diskus) or after 2 months (100 mcg and 250 mcg diskus) from removal from protective foil pouch or when the dose counter reads “0” (whichever comes first); device is not reusable.

Flovent HFA: Store between 20°C and 25°C (68°F and 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F). Discard device when the dose counter reads “000”. Store with mouthpiece down. Do not expose to temperatures >120°F. Do not puncture or incinerate.

Drug Interactions

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

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

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

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

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

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

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

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

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

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

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

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

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

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

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

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

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

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

Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

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

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

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

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

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

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

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

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

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

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

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

Adverse Reactions

>10%:

Central nervous system: Fatigue (≤16%), malaise (≤16%), headache (2% to 14%)

Gastrointestinal: Oral candidiasis (≤31%)

Neuromuscular & skeletal: Arthralgia (≤17%), arthritis (≤17%), musculoskeletal pain (2% to 12%)

Respiratory: Sinus infection (≤33%), sinusitis (≤33%), upper respiratory tract infection (2% to 31%), throat irritation (<1% to 22%), nasal congestion (≥3% to 16%), nasopharyngitis (8% to 13%), rhinitis (<1% to 13%), bronchitis (≤12%)

1% to 10%:

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

Central nervous system: Pain (10%), voice disorder (≤9%), procedural pain (<1% to 3%)

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

Gastrointestinal: Nausea and vomiting (1% to 9%), viral gastrointestinal infection (3% to 5%), gastrointestinal distress (≤4%), gastrointestinal pain (≤4%), oropharyngeal candidiasis (3%), toothache (3%), viral gastroenteritis (3%), abdominal pain (≤3%)

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

Infection: Influenza (4% to 7%), viral infection (≤5%), abscess (≤1%)

Neuromuscular & skeletal: Muscle injury (≤5%), back pain (3%), herniated disk (≤1%)

Respiratory: Viral respiratory infection (1% to 9%), cough (≤9%), hoarseness (≤9%), pharyngitis (3% to 6%), upper respiratory tract inflammation (≤5%), oropharyngeal pain (3% to 4%), allergic rhinitis (≥3%)

Miscellaneous: Fever (1% to 7%), accidental injury (≤5%), amputation (≤1%)

<1% (Limited to important or life-threatening): Adrenocortical insufficiency, aggressive behavior, allergic skin reaction, aphonia, bacterial infection, bacterial reproductive infection, behavioral changes (very rare: includes hyperactivity and irritability in children), blepharoconjunctivitis, bronchospasm (immediate and delayed), cataract (long-term use), cholecystitis, Churg-Strauss syndrome, conjunctivitis, cranial nerve palsy, Cushingoid appearance, decreased bone mineral density (long-term use), decreased linear skeletal growth rate (children and adolescents), dental caries, dental discoloration, depression, dermatitis, drug toxicity, eosinophilia, esophageal candidiasis, exacerbation of asthma, folliculitis, fungal infection, glaucoma (long-term use), hematoma, HPA-axis suppression, hypercorticoidism, hyperglycemia, hypersensitivity reaction (immediate and delayed; includes ear, nose, and throat allergic disorders, anaphylaxis, angioedema, bronchospasm, hypotension, skin rash, urticaria), increased intraocular pressure (long-term use), inflammation (musculoskeletal), keratitis, migraine, oral mucosa ulcer, osteonecrosis (especially with current or past use of systemic steroids), osteoporosis, paradoxical bronchospasm, photodermatitis, pneumonia, polyp (ear, nose, throat), pressure-induced disorder, soft tissue injury, urinary tract infection, vasculitis, viral skin infection

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis in sensitive patients. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled corticosteroids due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections. Select surgical patients on long-term, high-dose, inhaled corticosteroid (ICS), should be given stress doses of hydrocortisone intravenously during the surgical period and the dose reduced rapidly within 24 hours after surgery (NAEPP, 2007).

• Bronchospasm: May occur with wheezing after inhalation; if this occurs, stop steroid and treat with a fast-acting bronchodilator.

• Hypersensitivity: Hypersensitivity reactions including, allergic dermatitis, anaphylaxis, angioedema, bronchospasm, flushing, hypotension, urticaria, and rash have been reported.

• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use if possible in patients with ocular herpes; active or quiescent tuberculosis infections of the respiratory tract; or viral, fungal, or bacterial or parasitic systemic infections (Flovent Diskus and Flovent HFA Canadian labeling contraindicates use with untreated respiratory infections). Exposure to chickenpox and measles should be avoided; if the patient is exposed, prophylaxis with varicella zoster immune globulin or pooled intramuscular immunoglobulin, respectively, may be indicated; if chickenpox develops, treatment with antiviral agents may be considered. With oral inhalation, local yeast infections (eg, oropharyngeal candidiasis) may occur; patient should rinse mouth with water and spit after each use to reduce incidence.

• Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered.

• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

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

Disease-related concerns:

• Asthma: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Not to be used in status asthmaticus or for the relief of acute bronchospasm.

• Bone mineral density: Use with caution in patients with major risk factors for decreased bone mineral count such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (eg, anticonvulsants or oral corticosteroids); long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.

• Cardiovascular disease: Use with caution in patients with HF; long-term use has been associated with fluid retention and hypertension.

• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, peptic ulcer, ulcerative colitis) due to perforation risk.

• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention. Impairment of liver function may lead to accumulation of fluticasone in plasma. Monitor patients for corticosteroid related adverse effects.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred, especially during initial treatment with corticosteroids.

• Myocardial infarct (MI): Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.

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

• Seizure disorders: Use with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.

• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Concurrent drug therapy issues:

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

Special populations:

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

Dosage form specific issues:

• Arnuity Ellipta and Flovent Diskus: Contains lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.

Other warnings/precautions:

• Discontinuation of systemic corticosteroids: Withdraw systemic corticosteroid therapy with gradual tapering of dose; consider reducing the daily prednisone dose by 2.5 to 5 mg on a weekly basis beginning after at least 1 week of inhalation therapy. Monitor lung function, beta-agonist use, asthma symptoms, and for signs and symptoms of adrenal insufficiency (fatigue, lassitude, weakness, nausea and vomiting, hypotension) during withdrawal.

• Transfer to oral inhaler: When transferring to oral inhaler, previously-suppressed allergic conditions (rhinitis, conjunctivitis, eczema) may be unmasked.

Monitoring Parameters

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Hypoadrenalism may occur in infants born to mothers receiving corticosteroids during pregnancy. Based on available data, an overall increased risk of congenital malformations or a decrease in fetal growth has not been associated with maternal use of inhaled corticosteroids during pregnancy (Bakhireva, 2005; NAEPP, 2005; Namazy, 2004). Uncontrolled asthma is associated with adverse events in pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low birth weight infants). Inhaled corticosteroids are recommended for the treatment of asthma during pregnancy (most information available using budesonide) (ACOG, 2008; NAEPP, 2005).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, pharyngitis, flu-like signs, rhinorrhea, or rhinitis. Have patient report immediately to prescriber signs of infection, severe loss of strength and energy, irritability, tremors, tachycardia, confusion, dizziness, sweating, redness or white patches in mouth or throat, bone pain, joint pain, vision changes, difficulty breathing, wheezing, or cough (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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