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
Synthetic fluorinated glucocorticoid.105
Uses for Flunisolide
Not indicated for relief of acute bronchospasm.105
Flunisolide Dosage and Administration
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Death has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.105 (See Withdrawal of Systemic Corticosteroid Therapy under Cautions.)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
Administer twice daily.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
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
No special population dosage recommendations at this time.105
Cautions for Flunisolide
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
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
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
Monitor infants born to women who receive corticosteroids during pregnancy for possible hypoadrenalism.105
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
Interactions for Flunisolide
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
2–4 weeks of continuous therapy may be required for optimum effectiveness.105
Distribution into milk unknown, but other corticosteroids distributed into milk.105
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
Following oral inhalation, <1% of dose excreted in urine.105
Approximately 1.3–1.7 hours.105
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
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.)
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.
80 mcg (of flunisolide) per metered spray
Aerospan Inhalation Aerosol (with hydrofluoroalkane propellant)
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.
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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.