Generic Name: Flunisolide
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

Introduction

Synthetic fluorinated glucocorticoid.105

Uses for AeroBid

Asthma

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

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

Not indicated for relief of acute bronchospasm.105

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  • Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.105 (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)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

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

Interactions for AeroBid

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

AeroBid 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.

Flunisolide Hemihydrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Aerosol

80 mcg (of flunisolide) per metered spray

Aerospan Inhalation Aerosol (with hydrofluoroalkane propellant)

Acton

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 22, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

100. National Asthma Education and Prevention Program. Expert panel report II: guidelines for the diagnosis and management of asthma. Bethesda, MD: National Institutes of Health; 1997 Feb.

101. National Asthma Education Program. Executive summary: guidelines for the diagnosis and management of asthma. NIH Publication No. 94-3042A. Washington, DC: US Government Printing Office; 1994 Jul.

102. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention NHLBI/WHO Workshop Report. Bethesda, MD: National Institutes of Health. 2002 Feb. NIH/NHLBI Publication No. 02-3659. Available at http://www.ginasthma.com. Accessed Sep. 26, 2002.

103. British Thoracic Society. Guidelines on the management of asthma. Thorax. 1993; 48(Suppl 2):S1-24.

104. National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma. Update on selected topics-2002. Bethesda, MD: National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Coordinating Committee; 2003 Jun. Available from National Heart, Lung, and Blood Institute Information Center, NIH Publication No. 02-5074. Also available at . Accessed 2006 Jan. 5.

105. Acton Pharmaceuticals, Inc. Aerospan (flunisolide) inhalation aerosol prescribing information. Marlborough, MA; 2013 Aug.

106. Acton Pharmaceuticals, Inc, Marlborough, MA: Personal communication.

107. National Asthma Education and Prevention Program. Expert panel report III: guidelines for the diagnosis and management of asthma. 2007 Aug. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute. Available from website. Accessed 2013 Sep 19.

109. National Institutes of Health, National Heart, Lung, and Blood Institute. Global initiative for asthma: global strategy for asthma management and prevention. Bethesda, MD: National Institutes of Health. 2012 Dec. Available from website. Accessed 2013 Sep 19.

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