Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Aerosol Solution, Inhalation:
Aerospan: 80 mcg/actuation (5.1 g [DSC], 8.9 g [DSC])
Pharmacology
Mechanism of Action
Decreases airway inflammation by suppression of endogenous inflammatory mediators (kinins, histamine, liposomal enzymes, prostaglandins). Inhibits inflammatory cell migration and reverses increased capillary permeability to decrease access of inflammatory cells to the site of inflammation; does not depress hypothalamus.
Pharmacokinetics/Pharmacodynamics
Absorption
Rapid
Distribution
Extensive; Vd: 170-350 L
Metabolism
Rapid and extensive hepatic metabolism via CYP3A4 to a minimally active metabolite (6 beta-OH flunisolide); also undergoes conjugation
Excretion
Rapid; not detectable in plasma 12-hours post dose; urine (<1% as unchanged drug)
Time to Peak
Within 5-10 minutes
Half-Life Elimination
1.3-1.7 hours
Use: Labeled Indications
Asthma: Maintenance treatment of asthma as prophylactic therapy in patients ≥6 years.
Limitations of use: Not indicated for relief of acute bronchospasm.
Guideline recommendations:A low-dose inhaled corticosteroid (in addition to an as-needed short acting beta2-agonist) is the initial preferred long term control medication for children, adolescents, and adult patients with persistent asthma who are candidates for treatment according to a step-wise treatment approach (GINA 2018; NAEPP 2007).
Contraindications
Primary treatment of status asthmaticus or other acute asthma episodes of asthma requiring intensive measures
Dosage and Administration
Dosing: Adult
Note: Aerospan has been discontinued in the US for more than 1 year.
Note: The recommended starting dose is based upon previous asthma therapy and disease severity; may increase dose after 2 weeks of therapy in patients who are not adequately controlled. Titrate to the lowest effective dose once asthma is controlled.
Asthma: Oral inhalation: Metered-dose inhaler: Note: To decrease the severity or duration of an asthma exacerbation, may consider temporarily quadrupling the dose (early in the course of illness) in patients with mild to moderate asthma with a mild flare in symptoms. Reserve this approach for patients with no prior history of life-threatening asthma exacerbations, and in those with good self-management skills; return to baseline dose after normalization of symptoms or at a maximum of 14 days of the quadrupled dose (Fanta 2019; GINA 2018; McKeever 2018).
Patients not currently on inhaled corticosteroids: Initial: 160 mcg twice daily; maximum dose: 320 mcg twice daily.
Asthma Guidelines (NAEPP 2007): Metered-dose inhaler:
Low-dose therapy: 320 mcg/day in 2 divided doses
Medium-dose therapy: >320 to 640 mcg/day in 2 divided doses
High-dose therapy: >640 mcg/day in 2 divided doses
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Aerospan has been discontinued in the US for more than 1 year.
Asthma:
Maintenance therapy: Oral inhalation (80 mcg/inhalation): If adequate response is not seen after 3 to 4 weeks of initial dosage, increase dosage; doses should be titrated to the lowest effective dose once asthma is controlled.
Manufacturer's recommendations:
Children 6 to 11 years: Initial: One inhalation (80 mcg) twice daily; maximum daily dose: Two inhalations (160 mcg) twice daily (320 mcg/day).
Children ≥12 years and Adolescents: Initial: Two inhalations (160 mcg) twice daily; maximum daily dose: Four inhalations (320 mcg) twice daily (640 mcg/day).
Asthma Guidelines: National Asthma Education and Prevention Program (NAEPP 2007) (administer in divided doses twice daily):
Children 5 to 11 years:
"Low" dose: 160 mcg daily.
"Medium" dose: 320 mcg daily.
"High" dose: ≥640 mcg daily.
Children ≥12 years and Adolescents:
"Low" dose: 320 mcg daily.
"Medium" dose: >320 to 640 mcg daily.
"High" dose: >640 mcg daily.
Mild flare, exacerbation: Limited data available:
Children ≥12 years and Adolescents with mild to moderate asthma, no prior history of life-threatening asthma exacerbations, and with good self-management skills:
It is recommended to temporarily quadruple the inhaled corticosteroid dose early in the course of a mild flare to decrease the severity of an asthma exacerbation. After symptoms stabilize or after a maximum of 14 days of quadrupled dose, whichever occurs first, patients should be returned to their baseline dose (GINA 2019). Quadrupling the inhaled corticosteroid dose has been shown to decrease the severity of an asthma exacerbation in select patients. In a randomized trial of adolescents ≥16 years and adults (n=1,871), temporarily quadrupling the inhaled corticosteroid dose when asthma control began to deteriorate resulted in fewer severe asthma exacerbations (ie, less treatment with systemic glucocorticoids or unscheduled appointments for asthma) compared to patients who maintained their inhaled corticosteroid dose (McKeever 2018). No data for quadrupling the dose in patients <16 years of age has been published. Quintupling the dose of inhaled corticosteroids (fluticasone) in children 5 to 11 years of age was not shown to reduce the rate of severe exacerbations and may have been associated with adverse effects (decreased linear growth, particularly in patients <8 years of age) (GINA 2019; Jackson 2018).
Conversion from oral systemic corticosteroid to orally-inhaled corticosteroid: Initiation of oral inhalation therapy should begin in patients whose asthma is reasonably stabilized on oral corticosteroids (OCS). A gradual dose reduction of OCS should begin ~7 days after starting inhaled therapy. US labeling recommends reducing prednisone dose no more rapidly than ≤2.5 mg/day (or equivalent of other OCS) every 1 to 2 weeks in children ≥6 years and adolescents. If adrenal insufficiency occurs, temporarily increase the OCS dose and follow with a more gradual withdrawal. Note: When transitioning from systemic to inhaled corticosteroids, supplemental systemic corticosteroid therapy may be necessary during periods of stress or during severe asthma attacks.
Administration
Metered-dose inhaler: Shake well before using. Prime inhaler prior to first use and when the inhaler has not been used for >2 weeks by releasing 2 test sprays away from the face. Rinse mouth with water without swallowing after each use. Do not immerse the canister into water to determine remaining amount in the canister (ie, “float test”). Inhaler comes with a built-in spacer; do not use with any external spacer or holding chamber device; no cleaning is required. Discard inhaler after 60 or 120 sprays have been used even if canister is not empty (refer to product for number of actuations).
Storage
Store at 25°C (77°F); excursions are permitted to 15° to 30°C (59° to 86°F). For best results, the canister should be at room temperature before use. Discard inhaler when the labeled number of actuations have been used.
Contents under pressure; do not puncture. Do not use or store near heat or open flame. Protect from freezing temperatures and prolonged exposure to sunlight. Exposure to temperatures above 49°C (120°F) may cause bursting. Never throw into fire or incinerator.
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
Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy
Cosyntropin: Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. 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
Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. 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
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
Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy
Thiazide and Thiazide-Like Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tobacco (Smoked): May diminish the therapeutic effect of Corticosteroids (Orally Inhaled). Monitor therapy
Adverse Reactions
Frequency not always defined.
>10%:
Central nervous system: Headache (9% to 14%)
Respiratory: Pharyngitis (17% to 18%), rhinitis (4% to 16%)
1% to 10%:
Cardiovascular: Chest pain (1% to 3%), edema (1% to 3%), capillary fragility (≥1%), chest tightness (≥1%), hypertension (≥1%), palpitations (≥1%), peripheral edema (≥1%), tachycardia (≥1%)
Central nervous system: Pain (2% to 5%), dizziness (1% to 3%), insomnia (1% to 3%), migraine (1% to 3%), voice disorder (1% to 3%), anosmia (≥1%), anxiety (≥1%), depression (≥1%), fatigue (≥1%), hyperactivity (≥1%), hypoactivity (≥1%), irritability (≥1%), malaise (≥1%), mood changes (≥1%), numbness (≥1%), shakiness (≥1%), vertigo (≥1%)
Dermatologic: Skin rash (2% to 4%), erythema multiforme (1% to 3%), acne vulgaris (≥1%), diaphoresis (≥1%), eczema (≥1%), pruritus (≥1%), urticaria (≥1%)
Endocrine & metabolic: Weight gain (≥1%), adrenal suppression, adrenocortical insufficiency, growth suppression (children and adolescents), hypercorticoidism
Gastrointestinal: Vomiting (≤5%), dyspepsia (2% to 4%), abdominal pain (1% to 3%), diarrhea (1% to 3%), dysgeusia (1% to 3%), gastroenteritis (1% to 3%), nausea (1% to 3%), oral candidiasis (1% to 3%), ageusia (≥1%), constipation (≥1%), decreased appetite (≥1%), epigastric fullness (≥1%), flatulence (≥1%), glossitis (≥1%), heartburn (≥1%), mouth irritation (≥1%), sore throat (≥1%), stomach discomfort (≥1%), oropharyngeal candidiasis
Genitourinary: Urinary tract infection (1% to 4%), dysmenorrhea (1% to 3%), vaginitis (1% to 3%)
Hematologic & oncologic: Lymphadenopathy (≥1%)
Hypersensitivity: Hypersensitivity reaction (4% to 5%)
Infection: Bacterial infection (4%), infection (1% to 3%), cold symptoms (≥1%), influenza (≥1%)
Neuromuscular & skeletal: Back pain (1% to 3%), myalgia (1% to 3%), neck pain (1% to 3%), weakness (≥1%), decreased bone mineral density
Ophthalmic: Conjunctivitis (1% to 3%), blurred vision (≥1%), eye discomfort (≥1%), eye infection (≥1%), cataract, glaucoma, increased intraocular pressure
Otic: Otalgia (1% to 3%), otitis (≥1%)
Respiratory: Cough (9%), sinusitis (7% to 9%), epistaxis (3%), bronchitis (1% to 3%), laryngitis (1% to 3%), bronchospasm (≥1%), chest congestion (≥1%), dry throat (≥1%), dyspnea (≥1%), hoarseness (≥1%), increased bronchial secretions (≥1%), nasal congestion (≥1%), nasal mucosa irritation (≥1%), pleurisy (≥1%), pneumonia (≥1%), rhinorrhea (≥1%), sinus congestion (≥1%), sinus discomfort (≥1%), sinus drainage (≥1%), sinus infection (≥1%), sneezing (≥1%), throat irritation (≥1%), upper respiratory tract infection (≥1%), wheezing (≥1%), exacerbation of asthma
Miscellaneous: Fever (1% to 7%)
Warnings/Precautions
Concerns related to adverse effects:
- Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections (particularly gastroenteritis), or other conditions with severe electrolyte loss. 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: Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; reaction should be distinguished from inadequate response. If paradoxical bronchospasm occurs, discontinue flunisolide and institute alternative therapy.
- Immunosuppression: Prolonged use of corticosteroids may also 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 respiratory tuberculosis, or untreated viral, fungal, parasitic or bacterial systemic infections. Exposure to chickenpox and measles should be avoided; if the patient is exposed, prophylaxis with varicella zoster immune globulin or pooled intramuscular immunoglobulin, respectively, may be indicated; if chickenpox develops, treatment with antiviral agents may be considered.
- Oral candidiasis: Local oropharyngeal Candida albicans infections have been reported; if this occurs, treat appropriately while continuing therapy. Patients should be instructed to rinse mouth with water without swallowing after each use.
Disease-related concerns:
- Asthma: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Short-acting beta2-agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments. Use is contraindicated in status asthmaticus or 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.
- Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, glaucoma, and cataracts have occurred with prolonged use. Consider routine eye exams in chronic users.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Pediatric: Orally-inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients (~1 centimeter per year [range: 0.3 to 1.8 cm per year] and related to dose and duration of exposure). To minimize the systemic effects of orally-inhaled corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.
Other warnings/precautions:
- Discontinuation of therapy: A gradual tapering of dose may be required prior to discontinuing therapy; there have been reports of systemic corticosteroid withdrawal symptoms (eg, joint/muscle pain, lassitude, depression) when withdrawing oral inhalation therapy.
- Transfer to oral inhaler: When transferring to oral inhalation therapy from systemic corticosteroid therapy, previously suppressed allergic conditions (rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions) may be unmasked. Withdraw systemic corticosteroid therapy by gradually tapering the dose. Monitor lung function, beta-agonist use, asthma symptoms and for signs and symptoms of adrenal insufficiency (eg, fatigue, lassitude, weakness, nausea/vomiting, hypotension) during withdrawal.
Monitoring Parameters
Growth (adolescents and children via stadiometry); signs/symptoms of HPA axis suppression/adrenal insufficiency; signs/symptoms of oral candidiasis; possible eosinophilic conditions (including eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]); FEV1, peak flow, and/or other pulmonary function tests; asthma symptoms; bone mineral density; glaucoma/cataracts
Pregnancy
Pregnancy Considerations
Uncontrolled asthma is associated with adverse events in pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low birth weight infants). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications (ACOG 2008; GINA 2018).
Inhaled corticosteroids are recommended for the treatment of asthma during pregnancy (ACOG 2008; GINA 2018; Namazy 2016). Pregnant females adequately controlled on flunisolide for asthma may continue therapy; if initiating treatment during pregnancy, use of an agent with more data in pregnant females may be preferred (Namazy 2016).
Patient Education
- 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 stuffy nose, headache, sore throat, nausea, or runny nose. Have patient report immediately to prescriber signs of infection, signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), severe loss of strength and energy, severe fatigue, irritability, tremors, fast heartbeat, confusion, sweating, dizziness, thrush, difficulty breathing, wheezing, cough, bone pain, joint pain, or vision changes (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 health care 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.
