Brand name: Aerospan
Drug class: Adrenals
ATC class: R03BA03
VA class: NT200
Chemical name: (6α,11β,16α)-6-fluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis(oxy)]-pregna-1,4-diene-3,20-dione hemihydrate
Molecular formula: C₂₄H₃₁FO₆•½H₂O
CAS number: 77326-96-6

Medically reviewed by Drugs.com on Jan 12, 2024. Written by ASHP.

Introduction

Synthetic fluorinated glucocorticoid.

Uses for Flunisolide

Asthma

Long-term prevention of bronchospasm in patients with asthma.

In corticosteroid-dependent patients, may permit reduction in dosage or discontinuance of systemic corticosteroids.

Not indicated for relief of acute bronchospasm.

Flunisolide Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.

• After a satisfactory response is obtained, decrease dosage gradually to the lowest possible dosage that maintains an adequate clinical response. Achieve the lowest effective dosage, particularly in children, since inhaled corticosteroids have the potential to affect growth. (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. After at least 1 week, gradually withdraw the systemic corticosteroid.

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

• 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.

• Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly. (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. Supplemental systemic corticosteroid therapy may also be required during periods of stress.

Administration

Oral Inhalation

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

Administer twice daily.

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

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. Hold inhaler between thumb and index finger; shake immediately prior to use.

Inhale and exhale normally through the mouth and place mouthpiece of inhaler into the mouth with lips closed firmly around it. Begin to inhale slowly through the mouth, then press canister down with index finger for at least 1 second. 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.

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

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

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

Dosage

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

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

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

Pediatric Patients

Asthma

Oral Inhalation

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

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

Adults

Asthma

Oral Inhalation

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

Prescribing Limits

Pediatric Patients

Oral Inhalation

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

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

Adults

Oral Inhalation

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

Special Populations

No special population dosage recommendations at this time.

Related/similar drugs

prednisone, Breo Ellipta, Xopenex, Xolair, Dulera, Atrovent

Cautions for Flunisolide

Contraindications

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

Warnings/Precautions

Infections

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

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.

Acute Exacerbations of Asthma

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

Immunosuppressed Patients

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

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

Withdrawal of Systemic Corticosteroid Therapy

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

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).

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. Periodically monitor patients receiving such therapy for effects on the HPA axis. If such effects occur, slowly reduce dosage of oral inhalation therapy.

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

Reduction in Bone Mineral Density

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

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).

Ocular Effects

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

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

Acute Paradoxical Bronchospasm

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

Specific Populations

Pregnancy

Category C.

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

Lactation

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

Pediatric Use

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

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

Common Adverse Effects

Pharyngitis, rhinitis, headache, increased cough, sinusitis.

Drug Interactions

No formal drug interaction studies performed to date.

Metabolism thought to occur mainly via CYP3A4.

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.

Flunisolide Pharmacokinetics

Absorption

Bioavailability

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

Onset

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

Distribution

Extent

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

Elimination

Metabolism

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

Elimination Route

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

Half-life

Approximately 1.3–1.7 hours.

Stability

Storage

Oral Inhalation

Aerosol

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

Inhaler contents are under pressure. 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.

Actions

• Potent glucocorticoid and minimal mineralocorticoid activity.

• Demonstrates marked anti-inflammatory activity.

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

• Minimal systemic activity at recommended dosages.

Advice to Patients

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

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

• Importance of pediatric patients receiving therapy under adult supervision.

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

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

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

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

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

• 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.

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

• 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.

• 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.

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

• Importance of informing patients of potential for decreased BMD.

• Risk of reduction in growth velocity in children.

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

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

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

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

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

• Importance of informing patients of other precautionary information. (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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