Fluticasone (Flovent HFA, Flixotide) is a very potent steroid that is used for oral inhalation in patients with bronchospasm and uncontrolled asthma or COPD.

Fluticasone Inhaler (Flovent HFA, Flixotide) Uses:

• Asthma:

  • Flovent Diskus and Flovent HFA:
    • Maintenance treatment of asthma as prophylactic therapy in patients of 4 years or more than 4 years.
  • ArmonAir RespiClick and Arnuity Ellipta:
    • Maintenance treatment of asthma as prophylactic therapy in patients of 5 years or more than 5 years (Arnuity Ellipta) or ≥12 years (ArmonAir RespiClick).
  • 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 beta -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.

• Off Label Use of Fluticasone in Adults:

  • Used in chronic obstructive pulmonary disease (stable)
  • Used in eosinophilic esophagitis.

Fluticasone Inhaler Dose in adults

Note:

• Fluticasone furoate has a higher binding affinity for the lung glucocorticoid receptor compared to fluticasone propionate.
• The resulting enhanced affinity is reflected in the lower dose of fluticasone furoate compared to fluticasone propionate. Further studies are needed to elucidate a clinical effect.

Fluticasone Inhaler Dose in the treatment of Asthma: Oral inhalation:

Note:

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

• ArmonAir RespiClick (fluticasone propionate): Dry powder inhaler:

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

• No prior treatment with inhaled corticosteroids:
  • Initial:
    • 55 mcg twice in a day;
  • maximum:
    • 232 mcg two times in a day.
• Prior treatment with inhaled corticosteroid:
  • 55 mcg to 232 mcg two times in a day (base starting dosage on strength of previous inhaled corticosteroid and disease severity);
  • maximum:
    • 232 mcg two times in a day.

• Arnuity Ellipta (fluticasone furoate): Dry powder inhaler: Dosing based on previous asthma therapy:

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

• No prior treatment with inhaled corticosteroids:
  • Initial: 100 mcg once in a day;
  • maximum: 200 mcg per day.
• Prior treatment with inhaled corticosteroids:
  • Initial: 100 to 200 mcg once in a day;
  • maximum: 200 mcg per day
• Asthma guidelines: Global Initiative for Asthma guidelines (GINA 2018): Fluticasone furoate: Dry powder inhaler:
  • Low-dose therapy: 100 mcg per day
  • High-dose therapy: 200 mcg per day

• Flovent HFA (fluticasone propionate):

  • US labeling:

Note:

• Dosing based on previous asthma therapy and asthma severity.
• May increase dose after 2 weeks of therapy in patients who are not adequately controlled
  • Metered-dose inhaler:
    • Initial (patients with no prior inhaled corticosteroids): 88 mcg two times in a day;
    • maximum: 880 mcg two times a day.

  • Canadian labeling:

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

• • Metered-dose inhaler:
    • Mild asthma: 100 to 250 mcg two times in a day.
    • Moderate asthma: 250 to 500 mcg two times in  a day
    • Severe asthma: 500 mcg twice daily; may increase up to 1,000 mcg two times a day in very severe patients (eg, patients using oral corticosteroids [OCS]).
• Asthma guidelines:
  • National Asthma Education and Prevention Program guidelines: Fluticasone propionate (HFA): Metered-dose inhaler:
    • Low-dose therapy: 88 to 264 mcg per day in divided doses two times in  a day
    • Medium-dose therapy: >264 to 440 mcg per day in divided doses two times in  a day
    • High-dose therapy: >440 mcg per day in divided doses two times in  a day
  • Global Initiative for Asthma guidelines (GINA 2018): Fluticasone propionate (HFA): Metered-dose inhaler:
    • Low-dose therapy: 100 to 250 mcg per day
    • Medium-dose therapy: >250 to 500 mcg per day
    • High-dose therapy: >500 mcg per day

• Flovent Diskus (fluticasone propionate):

  • US labeling:

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

 

• Dry powder inhaler:
  • Initial (patients with no prior inhaled corticosteroids): 100 mcg two times in a day;
  • maximum: 1,000 mcg two times in a day.

  • Canadian labeling:

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

• Dry powder inhaler:
  • Mild asthma: 100 to 250 mcg two times in  a day.
  • Moderate asthma: 250 to 500 two times in  a day.
  • Severe asthma: 500 mcg two times in  a day; may increase up to 1,000 mcg two times in  a day in very severe patients (eg, patients using OCS).

  • Asthma guidelines:

    • National Asthma Education and Prevention Program guidelines: Fluticasone propionate: Dry powder inhaler:
      • Low-dose therapy: 100 to 300 mcg/day in divided doses two times in  a day
      • Medium-dose therapy: >300 to 500 mcg/day in divided doses two times in a day.
      • High-dose therapy: >500 mcg/day in divided doses two times in a day.
    • Global Initiative for Asthma guidelines (GINA 2018): Fluticasone propionate: Dry powder inhaler:
      • Low-dose therapy: 100 to 250 mcg per day
      • Medium-dose therapy: >250 to 500 mcg per day
      • High-dose therapy: >500 mcg per day

Fluticasone (Flovent HFA, Flixotide) Dose in the treatment of Chronic obstructive pulmonary disease (stable) (off-label):

• Fluticasone propionate:

  • Oral inhalation: 50 to 500 mcg per day in combination with a long-acting bronchodilator.

Fluticasone (Flovent HFA, Flixotide) Dose in the treatment of Eosinophilic esophagitis (off-label):

• Oral (off-label route): 440 to 880 mcg of aerosolized fluticasone swallowed (not inhaled) twice daily (880 to 1,760 mcg per day).

Fluticasone Inhaler Dose in Children

Fluticasone (Flovent HFA, Flixotide) Dose in the treatment of Asthma:

Note:

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

• Flovent HFA (Fluticasone propionate):

  • US labeling: Metered-dose inhaler: Oral inhalation:

    • Children 4 to 11 years:
      • 88 mcg two times in  a day
    • Children ≥12 years and Adolescents:
      • Initial: 88 mcg two times in  a day;
      • may start doses above 88 mcg twice daily in poorly controlled patients or in those who previously required higher doses of inhaled corticosteroids;
      • maximum dose: 880 mcg two times in  a day

  • Canadian labeling: Metered-dose inhaler: Oral Inhalation:

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

    • Adolescents ≥16 years:

      • Mild asthma:
        • 100 to 250 mcg two times in  a day
      • Moderate asthma:
        • 250 to 500 mcg two times in  a day
      • Severe asthma:
        • 500 mcg twice daily;
        • may increase up to 1,000 mcg twice daily in very severe patients

  • Asthma Guidelines:

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

Note: Administer in divided doses twice daily:

• "Low" dose:

  • Infants and Children ≤4 years: 176 mcg per day
  • Children 5 to 11 years: 88 to 176 mcg per day
  • Children ≥12 years and Adolescents: 88 to 264 mcg per day

• "Medium" dose:

  • Infants and Children ≤11 years: >176 to 352 mcg per day
  • Children ≥12 years and Adolescents: >264 to 440 mcg per day

• "High" dose:

  • Infants and Children ≤11 years: >352 mcg per day
  • Children ≥12 years and Adolescents: >440 mcg per day

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

    • Children 4 to 5 years:
      • "Low" dose: 100 mcg per day
    • Children 6 to 11 years:
      • "Low" dose: 100 to 200 mcg per day
      • "Medium" dose: >200 to 500 mcg per day
      • "High" dose: >500 mcg per day
    • Children ≥12 years and Adolescents:
      • "Low" dose: 100 to 250 mcg per day
      • "Medium" dose: >250 to 500 mcg per day
      • "High" dose: >500 mcg per day

• Flovent Diskus (Fluticasone propionate):

  • US labeling: Dry powder inhaler: Oral inhalation:

    • Children 4 to 11 years:
      • Initial: 50 mcg two times in a day;
      • doses above 50 mcg two times in a day may be considered in patients poorly controlled or in those who previously required higher doses of inhaled corticosteroids;
      • maximum dose: 100 mcg two times in a day
    • Children ≥12 years and Adolescents:
      • Initial: 100 mcg two times in a day;
      • doses above 100 mcg two times in a day may be considered in poorly controlled patients or in those who previously required higher doses of inhaled corticosteroids;
      • maximum dose: 1,000 mcg two times in a day.

  • Canadian labeling: Dry powder inhaler: Oral inhalation:

    • Children ≥4 years and Adolescents <16 years:
      • Initial: 100 mcg two times in a day;
      • may increase up to 200 mcg two times in a day if required.
    • Adolescents ≥16 years:
      • Mild asthma: 100 to 250 mcg two times in a day
      • Moderate asthma: 250 to 500 mcg two times in a day
      • Severe asthma: 500 mcg two times in a day; may increase up to 1,000 mcg two times in a day in very severe patients

  • Asthma Guidelines:

    • National Asthma Education and Prevention Program Guidelines (NAEPP 2007): Dry powder inhaler:

Note: Administer in divided doses two times in a day:

• Children 5 to 11 years:

  • "Low" dose: 100 to 200 mcg per day
  • "Medium" dose: >200 to 400 mcg per day
  • "High" dose: >400 mcg per day

• Children ≥12 years and Adolescents:

  • "Low" dose: 100 to 300 mcg per day
  • "Medium" dose: >300 to 500 mcg per day
  • "High" dose: >500 mcg per day

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

    • Children 6 to 11 years:

      • "Low" dose: 100 to 200 mcg per day
      • "Medium" dose: >200 to 400 mcg per day
      • “High" dose: >400 mcg per day

    • Children ≥12 years and Adolescents:

      • "Low" dose: 100 to 250 mcg per day
      • "Medium" dose: >250 to 500 mcg per day
      • "High" dose: >500 mcg per day

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

  • Children 5 to 11 years:
    • 50 mcg once in a day
  • Children ≥12 years and Adolescents:
    • Initial: 100 mcg once in a day;
    • doses above 100 mcg once in a day may be considered in poorly-controlled patients or in those who previously required higher doses of inhaled corticosteroids.
    • Maximum dose: 200 mcg once in a day.

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

    • Children ≥12 years and Adolescents:

      • "Low" dose: 100 mcg per day
      • "High" dose: 200 mcg per day

• ArmonAir RespiClick (fluticasone propionate): Dry powder inhaler:

  • Children ≥12 years and Adolescents: Oral inhalation: Dosing based on previous asthma therapy:

    • No prior treatment with inhaled corticosteroids:
      • Initial: 55 mcg two times in a day.;
      • maximum: 232 mcg two times in a day.
    • Prior treatment with inhaled corticosteroid:
      • 55 mcg to 232 mcg two times in a day. (base starting dosage on strength of previous inhaled corticosteroid and disease severity);
      • maximum: 232 mcg twice daily

Fluticasone (Flovent HFA, Flixotide) Dose in the treatment of Bronchopulmonary dysplasia (BPD): Limited data available:

• Infants:

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

  • Bodyweight:

    • 5 to 1.2 kg:
      • 125 mcg every 12 hours for 3 weeks, followed by 125 mcg once in a day for the 4th week
    • ≥1.2 kg:
      • 250 mcg every 12 hours for 3 weeks, followed by 250 mcg once in a day for the 4th week

Fluticasone (Flovent HFA, Flixotide) Dose in the treatment of Eosinophilic esophagitis: Limited data available: Oral (swallowed):

Note:

• Patients use an oral inhaler without a spacer and swallow the medication.
• Optimal dose and dosing regimen are not established:

• General dosing range:

  • Children and Adolescents:
    • 88 to 440 mcg twice to four times daily;
    • maximum daily dose: 1,760 mcg/day.
    • Doses as high as 880 mcg twice daily have been reported.

• Age-based dosing:

  • Twice daily dosing:

    • Children 2 to 4 years: 88 mcg two times in a day.
    • Children 5 to 10 years: 220 mcg two times in a day.
    • Children ≥11 years and Adolescents: 440 mcg two times in a day.

  • Four times daily dosing:

    • Children ≤10 years:
      • 220 mcg 4 times daily for 4 weeks, 220 mcg 3 times daily for 3 weeks, 220 mcg two times in a day for 3 weeks, 220 mcg daily for 2 weeks
    • Children ≥11 years and Adolescents:
      • 440 mcg 4 times daily for 4 weeks, 440 mcg 3 times daily for 3 weeks, 440 mcg two times in a day. for 3 weeks, 440 mcg daily for 2 weeks

Fluticasone (Flovent HFA, Flixotide) Pregnancy Risk Category: B3

• Poorly managed asthma or exacerbations of asthma may pose a greater risk to the fetus/maternal health than medications that are properly used.
• For the treatment of asthma in pregnancy, it is recommended to take inhaled corticosteroids.
• After maternal oral inhalation, fluticasone can be detected within cord blood.
• Unfavorable pregnancy outcomes might result from uncontrolled asthma (increased chance of perinatal death, preeclampsia and preterm births, low birth weight infants).
• Fluticasone can be continued by pregnant women who are asthma-controlled.
• However, if the mother is not able to control her asthma symptoms with fluticasone, it may be possible to start treatment.

Fluticasone use during breastfeeding:

• It is unknown if enough fluticasone is absorbed by inhalation to make breast milk detectable. Human milk contains systemic corticosteroids.
• Breastfeeding is safe and healthy.
• Breastfeeding should be encouraged for women with asthma.
• According to the manufacturer of the product, when deciding whether to continue or stop breastfeeding during therapy, it should consider the risks to infant exposure, the benefits to the infant and the benefits to the mother.

Fluticasone (Flovent HFA, Flixotide) Dose in Kidney Disease:

• Arnuity Ellipta:
  • No dosage adjustment required.
• ArmonAir RespiClick, Flovent Diskus, and Flovent HFA:
  • The manufacturer's labeling doesn't provide any dosage adjustments (has not been studied).

Fluticasone (Flovent HFA, Flixotide) Dose in Liver disease:

• The manufacturer's labeling doesn't provide any dosage adjustments (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's product labeling indicates that systemic exposure is increased up to 3-fold. Use with caution and closely monitor.

Common Side Effects of Fluticasone (Flovent HFA, Flixotide):

• Central Nervous System:

  • Fatigue
  • Malaise
  • Headache

• Gastrointestinal:

  • Oral Candidiasis

• Neuromuscular & Skeletal:

  • Arthralgia
  • Musculoskeletal Pain

• Respiratory:

  • Sinus Infection
  • Throat Irritation
  • Nasal Congestion
  • Rhinitis
  • Sinusitis
  • Upper Respiratory Tract Infection

Less Common Side Effects Of Fluticasone (Flovent HFA, Flixotide):

• Cardiovascular:

  • Hypertension
  • Subarachnoid Hemorrhage

• Central Nervous System:

  • Pain
  • Voice Disorder
  • Dizziness

• Dermatologic:

  • Skin Rash
  • Pruritus

• Gastrointestinal:

  • Nausea And Vomiting
  • Viral Gastrointestinal Infection
  • Viral Gastroenteritis
  • Gastrointestinal Distress
  • Gastrointestinal Pain
  • Oropharyngeal Candidiasis
  • Toothache

• Hematologic & Oncologic:

  • Malignant Neoplasm Of Breast

• Infection:

  • Viral Infection
  • Influenza
  • Abscess

• Neuromuscular & Skeletal:

  • Muscle Injury
  • Muscle Spasm
  • Sprain
  • Limb Pain

• Respiratory:

  • Hoarseness
  • Cough
  • Upper Respiratory Tract Inflammation
  • Oropharyngeal Pain
  • Epistaxis
  • Viral Respiratory Tract Infection
  • Nasopharyngitis
  • Bronchitis
  • Pharyngitis
  • Respiratory Tract Infection

• Miscellaneous:

  • Fever
  • Accidental Injury

Side effects of Fluticasone (Frequency Not Defined):

• Cardiovascular:

  • Edema
  • Palpitations

• Central Nervous System:

  • Migraine
  • Mood Disorder
  • Mouth Pain

• Dermatologic:

  • Acne Vulgaris
  • Dermatitis
  • Photodermatitis
  • Viral Skin Infection
  • Dermatologic Disorders
  • Eczema
  • Folliculitis

• Endocrine & Metabolic:

  • Cushingoid Appearance
  • Fluid Volume Disorder
  • Weight Gain

• Gastrointestinal:

  • Change In Appetite
  • Diarrhea
  • Tongue Disease
  • Dyspepsia
  • Gastrointestinal Signs And Symptoms
  • Oral Mucosal Erythema
  • Oral Mucosa Ulcer
  • Oral Rash

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Polyp

• Infection:

  • Bacterial Infection
  • Bacterial Reproductive Infection
  • Fungal Infection

• Ophthalmic:

  • Blepharoconjunctivitis
  • Conjunctivitis
  • Keratitis

• Respiratory:

  • Allergic Rhinitis
  • Constriction Of The Pharynx
  • ENT Signs And Symptoms
  • Laryngitis
  • Rhinorrhea

• Miscellaneous:

  • Soft Tissue Injury
  • Swelling

Contraindications to Fluticasone (Flovent HFA, Flixotide):

• Hypersensitivity to fluticasone and any component of the formulation
• Hypersensitivity to milk proteins and lactose (Flovent, DiskusArmonAir RespiClick; Arnuity Ellipta);
• Primary treatment for status asthmaticus and other acute episodes of asthma requires intensive measures.

Canadian labeling: Additional contraindications not in US labeling

• Flovent HFA, Flovent Diskus
  • Untreated tubercular, fungal, or bacterial infections of the respiratory system.

Warnings and precautions

• Suppression of the adrenals:

  • May cause hypercortisolism or suppression of the hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods.
  • Patients who are being transferred from systemic to inhaled corticosteroids must be careful.
  • This is brought on by potential adrenal insufficiency, steroid withdrawal, and a rise in allergic reactions.
  • An adrenal crisis may result from HPA axis suppression.
  • It is important to withdraw and stop using a corticosteroid slowly and carefully.
  • Prednisone may make adult patients more susceptible if they are taking >=20mg of prednisone daily (or an equivalent).
  • Stress doses of hydrocortisone should be given intravenously to ICS patients who are taking long-term, high-dose inhaled corticosteroids. Within 24 hours, the dose should be lowered.
  • Asthmatic patients who have been treated with systemic corticosteroids and aerosol steroids have experienced fatalities.
  • Aerosol steroids can't deliver the systemic steroid needed to treat individuals with severe electrolyte loss due to trauma, surgery, infections (particularly gastroenteritis), or other illnesses.

• Bronchospasm

  • Inhaled bronchodilators can cause paradoxical bronchospasm, which could be potentially life-threatening.
  • The inadequate response should be distinguished from the inappropriate reaction.
  • Fluticasone should be stopped if paradoxical bronchospasm is experienced.

• Hypersensitivity

  • Anaphylaxis may be possible due to immediate hypersensitivity reactions, such as hypotension, rash or urticariaangioedema.

• Immunosuppression:

  • Patients with active or quiescent tuberculosis infections or respiratory tract infections, or viral, fungal or bacterial systemic infections should be avoided.
  • Corticosteroids can increase the risk of secondary infections, mask acute infections (including fungal infections), prolong and exacerbate viral infections, and limit vaccine response.
  • Avoid exposure to the measles and chickenpox. Prophylaxis may be advised if the patient has received either pooled intranamuscular immunoglobulin or varicella-zoster immunoglobulin. If chickenpox appears, treatment with antiviral medications might also be taken into account.

• Oral candidiasis:

  • There have been reports of localised Candida infections in the oropharynx. If this occurs, keep up your therapy.
  • Patients should be instructed to rinse their mouths with water and not swallow after each use.

• Vasculitis:

  • Eosinophilic polyangiitis, formerly known as Churg Strauss, and other systemic, eosinophilic diseases can occasionally lead to vasculitis.
  • Following inhaled corticosteroid therapy, it is common to experience a decrease or withdrawal of oral corticosteroid treatment.

• Asthma

  • During severe asthma attacks or stress, you may need to take oral or parenteral steroids.
  • It is not recommended to use during asthmatic status or other acute episodes that require intensive care.
  • Short-acting beta-agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments.

• Bone mineral density:

  • Patients who have major risk factors, such as extended immobility, family history, osteoporosis, a postmenopausal condition, smoking, poor nutrition, or long-term use of oral corticosteroids and anticonvulsants (e.g., anticonvulsants), should be closely monitored.
  • Long-term inhaled corticosteroids use has been linked to a decrease in bone mineral density.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.
  • Fluticasone may build up in the plasma if there is an impairment of liver function.

• Ocular disease:

  • Patients with cataracts or glaucoma should be cautious; patients who have experienced increased intraocular pressure, cataracts, and glaucoma with long-term use of the device should be aware.
  • Routine eye exams are recommended for chronic users.

• Pneumonia:

  • Inhaled corticosteroids, including fluticasone, have been linked to an increased risk of developing pneumonia in some long-term studies of COPD patients.
  • A study that looked at fluticasone and inhaled corticosteroid results in a decrease in the risk of this happening was also done.

Fluticasone (oral inhalation): Drug Interaction

Risk Factor C (Monitor therapy)
Amphotericin B	Amphotericin B's hypokalemic impact may be increased by corticosteroids (oral inhalation).
Aprepitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Clofazimine	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
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.
Cosyntropin	Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin.
CYP3A4 Inhibitors (Moderate)	May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).
Deferasirox	Corticosteroids may intensify Deferasirox's negative/toxic effects. Particularly, there may be a higher risk of GI bleeding or ulcers.
Denosumab	Immunosuppressants' harmful or toxic effects might be amplified. Particularly, there may be a higher risk for life-threatening infections.
Duvelisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Loop Diuretics	Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Loop Diuretics.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ocrelizumab	Could make immunosuppressive drugs work more effectively.
Palbociclib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Pidotimod	Pidotimod's therapeutic impact may be reduced by immunosuppressants.
Ritodrine	Corticosteroids may intensify Ritodrine's harmful or hazardous effects.
Simeprevir	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Thiazide and Thiazide-Like Diuretics	Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics.
Tobacco (Smoked)	May diminish the therapeutic effect of Corticosteroids (Orally Inhaled).
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Baricitinib's immunosuppressive impact may be enhanced by immunosuppressants. Treatment: It is not advised to combine baricitinib with strong immunosuppressants like azathioprine or cyclosporine. Methotrexate or nonbiologic disease-modifying antirheumatic medicines (DMARDs) may be used along with antirheumatic dosages.
CYP3A4 Inhibitors (Strong)	Fluticasone serum concentration might rise (Oral Inhalation). Treatment: It is not advised to use oral fluticasone propionate in combination with potent CYP3A4 inhibitors. Fluticasone furoate should be used cautiously when combined with potent CYP3A4 inhibitors. When utilising such a combination, keep a closer eye on the patients.
Echinacea	May lessen immunosuppressants' therapeutic impact.
Fingolimod	The immunosuppressive effect of Fingolimod may be strengthened by immunosuppressants. Management: When at all possible, refrain from using fingolimod and other immunosuppressants together. In case of combination, closely watch patients for cumulative immunosuppressive effects (eg, infections).
Hyaluronidase	The therapeutic benefit of hyaluronidase may be reduced by corticosteroids. Treatment: Standard doses of hyaluronidase may not produce the desired clinical response in patients using corticosteroids (especially at higher doses). Hyaluronidase may be needed at higher doses.
Leflunomide	Immunosuppressants may intensify Leflunomide's negative/toxic effects. In particular, there may be an elevated risk for hematologic toxicity, including pancytopenia, agranulocytosis, and/or thrombocytopenia. Management: When treating patients who are also taking immunosuppressants, you might choose to skip the leflunomide loading dosage. Patients who take leflunomide and another immunosuppressant should have their bone marrow function checked at least once a month.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Sipuleucel-T	Immunosuppressants may reduce Sipuleucel-therapeutic T's impact. Prior to starting sipuleucel-T therapy, evaluate patients to determine whether it is medically suitable to reduce or stop immunosuppressant therapy.
Stiripentol	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation.
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.
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.
Risk Factor X (Avoid combination)
Aldesleukin	Corticosteroids may diminish the antineoplastic effect of Aldesleukin.
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cobicistat	May increase the serum concentration of Fluticasone (Oral Inhalation).
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Desmopressin	Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin.
Fusidic Acid (Systemic)	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Idelalisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Loxapine	The negative or hazardous effects of loxapine may be increased by medications for airway disease. More precisely, the usage of Agents to Treat Airway Disease is probably a symptom of someone who is more likely to be susceptible to substantial bronchospasm from inhaling loxapine. Management: This only applies to the inhaled version of loxapine sold under the brand name Adasuve. The non-inhaled loxapine formulations are exempt from this rule.
Natalizumab	Immunosuppressants may intensify Natalizumab's harmful or hazardous effects. In particular, there may be an elevated risk of concomitant infection.
Pimecrolimus	Immunosuppressants' harmful or toxic effects might be amplified.
Tacrolimus (Topical)	Immunosuppressants' harmful or toxic effects might be amplified.
Tipranavir	Fluticasone serum concentration might rise (Oral Inhalation).

 

Monitoring parameters:

• Growth (adolescents and children via stadiometry);
• signs and symptoms of HPA axis suppression/adrenal insufficiency;
• signs/symptoms of oral candidiasis;
• possible eosinophilic conditions (including ChurgStrauss syndrome);
• FEV-1,
• peak flow, and/or other pulmonary function tests;
• asthma symptoms;
• bone mineral density;
• hepatic impairment;
• glaucoma and cataracts

How to administer Fluticasone?

Oral inhalation:

Dry powder inhaler:

ArmonAir RespiClick:

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

Arnuity Ellipta:

• Administer the dose at the same time every day.
• Do not shake the inhaler.
• When ready to use, open, and prepare the mouthpiece of the inhaler and slide the cover down to activate the first dose.
• Exhale fully (not into mouthpiece), take one deep breath through the mouth without blocking air vents and hold the 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 the 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" (the device is not reusable).

Flovent Diskus:

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

Metered-dose inhaler:

Flovent HFA:

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

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.

Mechanism of action of Fluticasone (Flovent HFA, Flixotide):

• Fluticasone is one of a number of corticosteroids which uses a fluorocarbothioate ester linkage at the 17-carbon position.
• It has extremely potent vasoconstrictive as well as anti-inflammatory properties. Fluticasone inhaled is effective because of its direct local effects.

The onset of action:

• The maximal benefit may take 1 to 2 weeks or longer

Absorption:

• Absorbed systemically primarily via lungs (Flovent Diskus: ~18 percent );
• minimal GI absorption ( less than 1 percent ) due to pre-systemic metabolism

Protein binding:

• more than 99 percent.

Metabolism:

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

Bioavailability:

• Oral inhalation: 13.9 percent ;
• Flovent Diskus: ~8 percent

Half-life elimination: IV: ~8 hours; Oral inhalation (plasma elimination phase following repeat dosing): 24 hours (ArmonAir RespiClick: ~11.2 hours) Time to peak, plasma:

• 0.5 to 1 hour

Excretion:

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

International Brand Names of Fluticasone:

• ArmonAir RespiClick 113
• ArmonAir RespiClick 232
• Flovent Diskus
• Allegro
• Allevisone
• Arnuity
• Arnuity Ellipta
• ArmonAir RespiClick 55
• Arnuity Ellipta
• Flovent Diskus
• Flovent HFA
• Arnuity Ellipta
• Atemur Mite
• Axotide
• Dalman AQ
• Flixotaide
• Flixotide
• Flixotide Inhaler
• Flixotide Nebules
• Flixovate
• Flohale
• Flomist
• Flutivate
• Futisone
• Lutisone
• Medicort
• Meseca
• Nasofan
• Rheoran F
• Flutaide
• Flutica
• Flutico
• Flutide
• Flutimar HFA
• Flutitrim
• Zoflut

Fluticasone Brand Names in Pakistan:

Fluticasone Propionate Inhaler 50 mcg/actu
Flixotide	Glaxosmithkline

 

Fluticasone Propionate Inhaler 125 mcg/actu
Flixotide	Glaxosmithkline

 

Fluticasone Propionate Inhaler 250 mcg/actu
Flixotide	Glaxosmithkline