Brand name: Aerospan
Drug class: Adrenals

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Synthetic fluorinated glucocorticoid.¹⁰⁵

Uses for Flunisolide (Oral Inhalation)

Asthma

Long-term prevention of bronchospasm in patients with asthma.^{105 107}

In corticosteroid-dependent patients, may permit reduction in dosage or discontinuance of systemic corticosteroids.^{105 107}

Not indicated for relief of acute bronchospasm.¹⁰⁵

Flunisolide (Oral Inhalation) Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.¹⁰⁵

• After a satisfactory response is obtained, decrease dosage gradually to the lowest possible dosage that maintains an adequate clinical response.¹⁰⁵ Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth.¹⁰⁵ (See Pediatric Use under Cautions.)

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

• When switching from systemic corticosteroids to orally inhaled flunisolide, initially administer oral inhalation concurrently with maintenance dosage of systemic corticosteroid.¹⁰⁵ After at least 1 week, gradually withdraw the systemic corticosteroid.¹⁰⁵

• Decrements not to exceed 2.5 mg of prednisone (or its equivalent) every week in patients receiving the oral inhalation.¹⁰⁵

• During withdrawal of oral therapy, symptoms of systemic corticosteroid withdrawal may occur despite maintenance or even improvement in pulmonary function; continue oral inhalation therapy but monitor for objective signs of adrenal insufficiency.¹⁰⁵

• Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.¹⁰⁵ (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)

• If exacerbations of asthma occur after transfer to oral inhalation therapy, administer short courses of systemic corticosteroids, then taper dosage as symptoms subside.¹⁰⁵ Supplemental systemic corticosteroid therapy may also be required during periods of stress.¹⁰⁵

Administration

Oral Inhalation

Administer by oral inhalation using a metered-dose oral aerosol inhaler with internal spacer.¹⁰⁵ Do not use this oral inhaler with external spacers or holding chambers.¹⁰⁵

Administer twice daily.¹⁰⁵

To prepare inhaler, pull purple actuator out from gray spacer; snap into place forming an “L” shape.¹⁰⁵ Ensure that lines on the spacer match up with lines on the actuator.¹⁰⁵

Before first use, and any time inhaler not used for >2 weeks, prime the inhaler with 2 test sprays by pressing down on the metal canister 2 times, holding for 1 second each time, with mouthpiece pointed away from face.¹⁰⁵ Hold inhaler between thumb and index finger; shake immediately prior to use.¹⁰⁵

Inhale and exhale normally through the mouth and place mouthpiece of inhaler into the mouth with lips closed firmly around it.¹⁰⁵ Begin to inhale slowly through the mouth, then press canister down with index finger for at least 1 second.¹⁰⁵ Continue to inhale through the mouth for 3 more seconds, then remove inhaler from the mouth, close the lips, and hold the breath for at least 10 seconds or as long as comfortable; then exhale and breathe normally.¹⁰⁵

If additional inhalations are required, wait 20 seconds between inhalations, shake inhaler again, and repeat procedure.¹⁰⁵

Following each treatment, rinse mouth thoroughly with water and expectorate to remove drug deposited in the oropharyngeal area.¹⁰⁵ Brush teeth if desired.¹⁰⁵

Appearance of white residue at mouthpiece opening and inside spacer is normal with use and does not affect inhaler performance.¹⁰⁵ Cleaning inhaler is not necessary.¹⁰⁵

Dosage

Available as flunisolide hemihydrate; dosage expressed in terms of flunisolide.¹⁰⁵

Oral inhalation aerosol delivers 80 mcg of flunisolide from the actuator (mouthpiece) per metered spray.¹⁰⁵ Commercially available aerosol inhaler delivers 60 metered sprays per 5.1-g canister or 120 metered sprays per 8.9-g canister.¹⁰⁵

Carefully adjust dosage according to individual requirements and response; titrate to lowest effective dosage to minimize potential for adverse systemic effects.¹⁰⁵

Pediatric Patients

Asthma

Oral Inhalation

Children 6–11 years of age: Initially, 80 mcg (1 spray) twice daily.¹⁰⁵ If required, dosage may be increased to 160 mcg (2 sprays) twice daily.¹⁰⁵

Adolescents ≥12 years of age: Initially, 160 mcg (2 sprays) twice daily.¹⁰⁵ If required, dosage may be increased to 320 mcg (4 sprays) twice daily.¹⁰⁵

Adults

Asthma

Oral Inhalation

Initially, 160 mcg (2 sprays) twice daily.¹⁰⁵ If required, dosage may be increased to 320 mcg (4 sprays) twice daily.¹⁰⁵

Prescribing Limits

Pediatric Patients

Oral Inhalation

Children 6–11 years of age: Maximum 160 mcg twice daily.¹⁰⁵ Dosages >160 mcg (2 sprays) twice daily (320 mcg total daily dosage) not evaluated.¹⁰⁵

Adolescents ≥12 years of age: Maximum 320 mcg twice daily.¹⁰⁵ Dosages >320 mcg (4 sprays) twice daily (640 mcg total daily dosage) not evaluated.¹⁰⁵

Adults

Oral Inhalation

Maximum 320 mcg twice daily.¹⁰⁵ Dosages >320 mcg (4 sprays) twice daily (640 mcg total daily dosage) not evaluated.¹⁰⁵

Special Populations

No special population dosage recommendations at this time.¹⁰⁵

Cautions for Flunisolide (Oral Inhalation)

Contraindications

• Primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures (e.g., oxygen, parenteral bronchodilators, IV corticosteroids) are required.^{105 107 109}

Warnings/Precautions

Infections

Localized fungal infections (Candida albicans or Aspergillus niger) of the mouth, pharynx, and occasionally the larynx reported.¹⁰⁵ If infection occurs, appropriate local or systemic antifungal treatment and/or temporary interruption of therapy may be required.¹⁰⁵

Use with caution, if at all, in patients with untreated active or quiescent Mycobacterium tuberculosis infections of the respiratory tract; untreated systemic fungal, bacterial, parasitic, or viral infections; or ocular herpes simplex.¹⁰⁵

Acute Exacerbations of Asthma

Treat acute asthma symptoms with a short-acting β₂-agonist bronchodilator.¹⁰⁵ If symptoms persist, promptly reevaluate asthma therapy and consider initiating systemic corticosteroids.¹⁰⁵

Immunosuppressed Patients

Increased susceptibility to infections in patients receiving immunosuppressant drugs compared with healthy individuals.¹⁰⁵ Certain infections (e.g., varicella [chickenpox], measles) can have a more serious (even fatal) outcome in such patients.¹⁰⁵

Avoid exposure to varicella and measles in previously unexposed patients who are not properly immunized.¹⁰⁵ If exposure to varicella (chickenpox) or measles occurs in susceptible patients, consider administering varicella zoster immune globulin (VZIG) or pooled immune globulin (IG), respectively.¹⁰⁵ Consider treatment with an antiviral agent if varicella develops.¹⁰⁵

Withdrawal of Systemic Corticosteroid Therapy

Possible corticosteroid withdrawal symptoms (e.g., joint or muscular pain, lassitude, depression);¹⁰⁵ acute adrenal insufficiency;¹⁰⁵ or symptomatic exacerbation of allergic conditions if prolonged systemic corticosteroid therapy is replaced with oral inhalation corticosteroid therapy.¹⁰⁵

Taper dosage of the systemic corticosteroid; carefully monitor patients during dosage reduction for objective signs of adrenal insufficiency (e.g., hypotension, fatigue, lassitude, weakness, nausea, vomiting).¹⁰⁵

Systemic Corticosteroid Effects

Administration of orally inhaled flunisolide, particularly at higher than recommended dosages, may result in manifestations of hypercorticism and suppression of HPA function.¹⁰⁵ Periodically monitor patients receiving such therapy for effects on the HPA axis.¹⁰⁵ If such effects occur, slowly reduce dosage of oral inhalation therapy.¹⁰⁵

Carefully monitor patients during periods of stress (e.g., infections, trauma, surgery) for manifestations of hypoadrenalism.¹⁰⁵

Reduction in Bone Mineral Density

Decreased bone mineral density (BMD) reported following long-term administration of inhaled corticosteroids, including flunisolide.¹⁰⁵

Monitor patients with risk factors for decreased BMD (e.g., prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, prolonged use of drugs [e.g., anticonvulsants, corticosteroids] that may reduce bone mass).¹⁰⁵

Ocular Effects

Glaucoma, increased IOP, and cataracts reported following long-term administration of inhaled corticosteroids, including flunisolide.¹⁰⁵

Closely monitor patients, especially those with vision changes or with history of increased IOP, glaucoma, or cataracts.¹⁰⁵

Acute Paradoxical Bronchospasm

Possible acute paradoxical bronchospasm.¹⁰⁵ If such a reaction occurs, discontinue orally inhaled flunisolide and initiate therapy with a short-acting inhaled bronchodilator immediately; institute alternative therapy.¹⁰⁵

Specific Populations

Pregnancy

Category C.¹⁰⁵

Monitor infants born to women who receive corticosteroids during pregnancy for possible hypoadrenalism.¹⁰⁵

Lactation

Not known whether distributed into milk.¹⁰⁵ Since other corticosteroids are distributed into milk, use caution in nursing women.¹⁰⁵

Pediatric Use

Safety and efficacy not established in children <6 years of age.¹⁰⁵

Periodically monitor (e.g., via stadiometry) the growth and development of children receiving orally inhaled flunisolide.¹⁰⁵ Weigh potential benefits of corticosteroid therapy against possibility of growth suppression and risks/benefits of treatment alternatives.¹⁰⁵ Use the lowest possible dosage that effectively controls asthma.¹⁰⁵

Common Adverse Effects

Pharyngitis,¹⁰⁵ rhinitis,¹⁰⁵ headache,¹⁰⁵ increased cough,¹⁰⁵ sinusitis.¹⁰⁵

Drug Interactions

No formal drug interaction studies performed to date.¹⁰⁶

Metabolism thought to occur mainly via CYP3A4.¹⁰⁵

Drugs Affecting Hepatic Microsomal Enzymes

Concomitant use of flunisolide and drugs that affect CYP3A4 could alter flunisolide metabolism, but orally inhaled flunisolide has limited potential to cause interactions with CYP3A4 at plasma concentrations achieved clinically.¹⁰⁶

Flunisolide (Oral Inhalation) Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral inhalation.¹⁰⁵ Oral bioavailability <7%.¹⁰⁵

Onset

2–4 weeks of continuous therapy may be required for optimum effectiveness.¹⁰⁵

Distribution

Extent

Distribution into milk unknown, but other corticosteroids distributed into milk.¹⁰⁵

Elimination

Metabolism

Rapidly and extensively metabolized in the liver to 6β-hydroxyflunisolide.¹⁰⁵ Metabolite has >200 times less corticosteroid potency than flunisolide.¹⁰⁵ Metabolism thought to occur via CYP isoenzymes (primarily CYP3A4).¹⁰⁵

Elimination Route

Following oral inhalation, <1% of dose excreted in urine.¹⁰⁵

Half-life

Approximately 1.3–1.7 hours.¹⁰⁵

Stability

Storage

Oral Inhalation

Aerosol

25°C (may be exposed to 15–30°C);¹⁰⁵ protect from excessive heat and freezing temperatures.¹⁰⁵ Avoid prolonged sunlight exposure.¹⁰⁵

Inhaler contents are under pressure.¹⁰⁵ Do not puncture, use, or store near heat or open flame; expose to temperatures >49°C; or place into a fire or incinerator for disposal.¹⁰⁵

Actions

• Potent glucocorticoid and minimal mineralocorticoid activity.¹⁰⁵

• Demonstrates marked anti-inflammatory activity.¹⁰⁵

• Improves lung function (e.g., FEV₁, morning peak expiratory flow).¹⁰⁵

• Minimal systemic activity at recommended dosages.¹⁰⁵

Advice to Patients

• Provide a copy of the manufacturer's patient information each time the drug is dispensed.¹⁰⁵ Importance of instructing patients to read the patient information prior to initiation of therapy and each time the prescription is refilled.¹⁰⁵

• Importance of adequate understanding of proper storage, preparation, and administration techniques, including use of the oral aerosol inhaler.¹⁰⁵

• Importance of pediatric patients receiving therapy under adult supervision.¹⁰⁵

• Risk of localized fungal infections of the mouth and pharynx.¹⁰⁵ Importance of rinsing the mouth after oral inhalation.¹⁰⁵ Importance of informing clinician if mouth becomes sore or develops a rash.¹⁰⁵

• Importance of advising patients that flunisolide oral inhalation must be used at regular intervals to be therapeutically effective.¹⁰⁵

• Importance of advising patients that 2–4 weeks of continuous therapy may be required for optimum effects to be achieved.¹⁰⁵

• Importance of not exceeding the recommended dosage and of contacting clinician immediately if asthma symptoms worsen or fail to improve.¹⁰⁵

• Importance of not discontinuing therapy or changing dosage without consulting clinician.¹⁰⁵

• Importance of advising patients not to use orally inhaled flunisolide as a bronchodilator and that the drug is not indicated for relief of acute bronchospasm.¹⁰⁵

• Importance of gradual withdrawal from systemic corticosteroids during transfer to orally inhaled flunisolide and of monitoring by clinician during such transfer of therapy.¹⁰⁵

• Advise patients being transferred from systemic to orally inhaled corticosteroids to carry special identification (e.g., card) indicating the need for supplementary systemic corticosteroids during stressful periods.¹⁰⁵

• Advise patients receiving orally inhaled flunisolide therapy who are currently being withdrawn from systemic corticosteroids to immediately resume therapy with systemic corticosteroids and to contact clinician for further instructions during stressful periods.¹⁰⁵

• Risk of systemic corticosteroid effects (e.g., hypercorticism, potentially life-threatening adrenal suppression).¹⁰⁵

• Importance of informing patients of potential for decreased BMD.¹⁰⁵

• Risk of reduction in growth velocity in children.¹⁰⁵

• Increased risk for development of cataracts or glaucoma with long-term use of inhaled corticosteroids.¹⁰⁵ Advise patients to consider the need for regular eye examinations.¹⁰⁵

• Importance of immunosuppressed patients avoiding exposure to chickenpox or measles, and if exposed, of immediately consulting clinician.¹⁰⁵

• Importance of advising immunosuppressed patients of potential worsening of existing tuberculosis; fungal, bacterial, parasitic, or viral infections; or ocular herpes simplex.¹⁰⁵

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹⁰⁵

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰⁵

• Importance of informing patients of other precautionary information.¹⁰⁵ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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