Synopsis: Flunisolide1, a derivative of fluocinolone acetonide, is advocated for intranasal inhalation for the treatment of perennial and seasonal allergic rhinitis. It is rapidly absorbed by all routes of administration, but it quickly undergoes extensive first-pass metabolism to a 6β-hydroxylated metabolite, which possesses only weak corticosteroid effects. Intranasal flunisolide relieves nasal symptoms (but not eye symptoms) in both perennial and seasonal allergic rhinitis, being most effective in patients who have an allergic component to their rhinitis; and like other intranasal corticosteroids it may reduce the need for systemic antihistamines in such patients, especially during peak pollen periods. A few well designed comparative studies have shown flunisolide to be as effective as intranasal beclomethasone, and (in a single study) more effective than intranasal sodium cromoglycate solution.
Only transient side effects have occurred, including nasal stinging and throat irritation. No Candida infections have been clinically apparent in short or longer term trials. Resting morning plasma cortisol levels have not been suppressed by usual therapeutic doses of intranasal flunisolide, but the drug’s effects on hypothalamo-pituitary-adrenal (HPA) axis integrity during conditions of stress have not been evaluated.
Pharmacology: In animal studies flunisolide has several hundred times the anti-inflammatory, thymolytic and anti-adrenocorticotrophic hormone activities of hydrocortisone. It has been shown in animal models to reduce inflammation after topical application, and in man to cause cutaneous vasoconstriction with an activity similar to beclomethasone dipropio-nate and triamcinolone acetonide. Inhaled flunisolide has an eosinophil suppressive potency one-third that seen with the intravenous route. Unlike systemically administered corticosteroids, inhaled flunisolide does not impair neutrophil chemotaxis.
Administration of intranasal flunisolide for several months did not produce drug related abnormalities on nasal biopsy. A small nasal septal perforation waxted in a single patient receiving flunisolide, but whether this was related to flunisolide treatment was unclear.
Pharmacokinetic Studies: Flunisolide is rapidly absorbed following oral ingestion and bronchial or intranasal inhalation. Systemic bioavailability is 21 %, 39 % and 49 % when it is administered orally, by inhalation and intranasally, respectively. After intranasal inhalation, peak plasma concentrations are reached in 10 to 30 minutes. Flunisolide has a relatively large volume of distribution (about 1.8L/kg) in man and is widely distributed to body tissues in rats. In man, it undergoes rapid and extensive first-pass metabolism to a 6β-hydroxylated metabolite, which has less than 0.01 times the potency of flunisolide, and is less than 3 times as potent as hydrocortisone. The plasma elimination half-life of flunisolide is about 1.8 hours by all routes of administration. After intravenous or oral administration flunisolide is excreted in the urine (about 50% ) and faeces (about 40%), mainly as the 6β-hydroxylated metabolite and conjugates.
Therapeutic Trials: Flunisolide has been studied in a number of placebo controlled trials and in a few well designed comparative studies with other agents. Intranasal flunisolide (150 to 300µg daily) was usually clearly more effective than a placebo in relieving most nasal symptoms of rhinitis (e.g. sneezing, stuffy or runny nose, nose blowing, postnasal drip), but not eye symptoms, and was judged superior to a placebo by about 70% of patients in most studies. It was particularly effective in rhinitis with a clearly demonstrable allergic component (e.g. high immunoglobulin E levels, eosinophilia, positive skin tests); indeed, it was ineffective in a single study conducted entirely in patients with nonallergic perennial rhinitis. As with other intranasal corticosteroids, the need for systemic antihistamines is often reduced in patients with allergic rhinitis receiving flunisolide. In a few well designed comparative studies, flunisolide was as effective as usual doses of intranasal beclomethasone dipropionate in seasonal allergic or perennial (usually allergic) rhinitis, and was more effective than in-tranasal sodium cromoglycate solution in a single study in seasonal allergic rhinitis.
Side Effects: Intranasal flunisolide is generally well tolerated, producing only transient nasal stinging and throat irritation. It has not altered haematological or biochemical laboratory parameters. No Candida infections were clinically apparent in rhinitis patients in the short or longer term (up to a year in a small number of patients) trials which have been reported, although Candida colonisation was present in 2 patients. However, such findings are not likely clinically important. Although resting morning plasma cortisol levels have not been suppressed by usual therapeutic doses of intranasal flunisolide, effects on hypothalamo-pituitary-adrenal axis integrity during conditions of stress in patients receiving flunisolide have not been evaluated.
Dosage: Flunisolide is available as a metered pump aerosol delivering 25µg per spray. In the treatment of rhinitis the recommended dosage is 2 sprays per nostril twice daily (200µg daily), increasing to 2 sprays 3 times daily if required. In children 1 spray 3 times daily is recommended.
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Backhouse, C.I.: Intra-nasal flunisolide in the treatment of allergic rhinitis in general practice. Current Medical Research and Opinion 6: 14–19(1979).
Bloom, F.L.; Cohan, R.H.; Leifer, K.N.; Spangler, D.L.; Rhoades, R.B. and Wittig, HJ.: Flunisolide aerosol in the treatment of perennial allergic rhinitis. Annals of Allergy 38: 408–412 (1977).
Brown, H.M.: Flunisolide compared with sodium cromoglycate in patients with seasonal allergic rhinitis. Unpublished data, on file Syntex (1980).
Brydøy, B. and Gronas, H.E.: Flunisolide nasal solution compared with beclomethasone in the treatment of seasonal rhinitis. Syntex, unpublished data (1980).
Butler, J. and Gray, C.H.: The metabolism of betamethasone. Journal of Endocrinology 46: 379–390 (1970).
Chaplin, M.D.; Cooper, W.C.; Segre, E.J.; Oren, J.; Jones, R.E. and Nerenberg, C.: Correlation of flunisolide nasal levels to eosinopenic response in man. Journal of Allergy and Clinical Immunology. In press (1980b).
Chaplin, M.; Matin, S.; Tokes, L.; Rooks, W. II; Swenson, E.; Maddox, M.; Chu, N.; Amos, B. and Bell, J.: Species variation in the first-pass metabolism of orally administered flunisolide (abstract No. 2073). Presented at the 7th International Congress of Pharmacology (Paris, 1978).
Chaplin, M.D.; Oren, J.; Cooper, W.C.; Segre, E.J. and Jones, R.E.: Correlation of plasma levels and eosinopenic response to flunisolide in normal volunteers (abstract No. 288). Journal of Allergy and Clinical Immunology 63: 219 (1979).
Chaplin, M.D.; Rooks, W. II; Swenson, E.W. and Chu, N.I.: Flunisolide metabolism and dynamics of a metabolite. Clinical Pharmacology and Therapeutics 27: 402–413 (1980).
Chu, N.I.; Amos, B.A.; Tokes, L.; Maddox, M.L.; Matin, S.B.; Hama, K.M.; Patterson, J.W.; Wagner, P.J.; Bell, J.P. and Chaplin, M.D.: Disposition of flunisolide in the rat, mouse, dog, rhesus monkey and cynomolgus monkey. Drug Metabolism and Disposition 7: 81–89 (1979).
Gale, A.E. and Harding, P.: Flunisolide intranasal solution combined with intrabronchial steroids in adults with both bronchial asthma and perennial rhinitis. Journal of Clinical Allergy, in press (1980).
Hansen, I. and Mygind, N.: Local effect of intranasal beclomethasone dipropionate aerosol in perennial rhinitis. Acta Allergol 29: 281–287 (1974).
Horan, J.D. and Johnson, J.D.: Flunisolide nasal spray in the treatment of perennial rhinitis. Canadian Medical Association Journal 119: 334–338 (1978).
Incaudo, G.; Schatz, M.; Yamamoto, F.; Mellon, M.; Crepea, S. and Johnson, J.D.: Intranasal flunisolide in the treatment of perennial rhinitis. Journal of Allergy and Clinical Immunology 65: 41–49 (1980).
Jones, L.M.; Spector, S.L.; English, G.M. and Taylor-Dawson, K.: Treatment of perennial rhinitis with flunisolide corticosteroid spray. Annals of Allergy 42: 139–144 (1979).
Kammermeyer, J.K.; Rajtora, D.W.; Anuras, J. and Richerson, H.B.: Clinical evaluation of intranasal topical flunisolide therapy in allergic rhinitis. Journal of Allergy and Clinical Immunology 59: 287–293(1977).
Kupfer, D. and Partridge, R.: 6-Beta-hydroxylation of triamcinolone acetonide by a hepatic enzyme system. The effect of phenobarbital and l-benzyl-2-thio-5,6-dihydromacil. Archives of Biochemistry and Biophysics 140: 23–28 (1970).
Livanou, T.; Ferrimar, D. and James, V.H.T.: The response to stress after corticosteroid therapy. Proceedings of the Royal Society of Medicine 43: 1013–1018 (1965).
McAllen, M.K.; Portillo, P.R.; Parr, E.J.; Seaton, A. and Engler, C.: Intranasal flunisolide, placebo and beclomethasone dipropionate in perennial rhinitis. British Journal of Diseases of the Chest 74: 32–36 (1980).
Mygind, N.; Hansen, I.; Pedersen, C.B.; Prytz, S. and Sorensen, H.: Intranasal beclomethasone dipropionate aerosol in allergic nasal diseases. Postgraduate Medical Journal 51(Suppl. 4): 107–110 (1975).
Norman, P.S.; Winkenwerder, W.L.; Agbayani, B.F. and Migeon, C.J.: Adrenal function during the use of dexamethasone aerosols in the treatment of ragweed hayfever. Journal of Allergy 40: 57 (1967).
Sahay, J.N.; Chatterjee, S.S. and Engler, C.: Flunisolide — a new intranasal steroid for the treatment of allergic rhinitis. Clinical Allergy 9: 17–24 (1979).
Sahay, J.N.; Chatterjee, S.S. and Engler, C.: A comparative trial of flunisolide and beclomethasone dipropionate in the treatment of perennial allergic rhinitis. Clinical Allergy 10: 65–70 (1980a).
Sahay, J.N.; Ibrahim, N.B.N.; Chatterjee, S.S.; Nassar, W.Y.; Lodge, K.V. and Jones, C.W.: Long-ternvstudy of flunisolide treatment in perennial rhinitis with special reference to nasal mucosal histology and morphology. Unpublished data, Syntex (1980b).
Sarsfield, J.K. and Thomson, G.E.: Flunisolide nasal spray for perennial rhinitis in children. British Medical Journal 2: 95–97 (1979).
Schultz, J.I.; Johnson, J.D. and Freedman, S.O.: Double-blind trial comparing flunisolide and placebo for the treatment of perennial rhinitis. Clinical Allergy 8: 313–320 (1978).
Shore, S.C. and Weinberg, E.G.: Beclomethasone dipropionate in the treatment of nasal allergy in children. Postgraduate Medical Journal 51(Suppl. 4): 111 (1975).
Siegel, S.; Katz, R.; Rachelefsky, G. and Crepea, S.: Flunisolide aerosol treatment of perennial allergic rhinitis in children (abstract No. 78). Journal of Allergy and Clinical Immunology 61: 152 (1978).
Slankard, M.L.; Siskind, G.W. and Dwortezky, M.: Flunisolide nasal spray in perennial rhinitis: effectiveness and nasal fungal growth (abstract No. 130). Journal of Allergy and Clinical Immunology 57: 242 (1976).
Smith, J.M.; Clegg, R.T.; Cook, N. and Butler, A.G.: Intranasal beclomethasone dipropionate in allergic rhinitis. British Medical Journal 2: 255 (1975).
Spector, S.: Flunisolide versus placebo: a long term, high dose study. Syntex, unpublished data (1977).
Strem, E.L.; Austrian, S.; Geller, G.R.; Johnson, J.D. and Crepea, S.: Flunisolide nasal spray for the treatment of children with seasonal allergic rhinitis. Annals of Allergy 41: 145–149 (1978).
Swenson, E.W.; Chaplin, M.D. and Jones, R.E.: The fate of an inhaled corticosteroid (abstract). American Review of Respiratory Disease 115(Suppl.): 76 (1977).
Sy, R.K.: Flunisolide intranasal spray in the treatment of perennial rhinitis. Archives of Otolaryngology 105: 649–653 (1979).
Turkeltaub, P.C.; Norman, P.S. and Crepea, S.: Treatment of ragweed hay fever with an intranasal spray containing flunisolide, a new synthetic corticosteroid. Journal of Allergy and Clinical Immunology 58: 597–606 (1976).
Turkeltaub, P.C.; Norman, P.S. and Crepea, S.: Treatment of perennial rhinitis with an intranasal spray containing flunisolide — a potent fluorinated steroid (abstract No. 262). Journal of Allergy and Clinical Immunology 63: 210–211 (1979).
Various sections of the manuscript reviewed by: F.L. Bloom, Allergy Associates, Sarasota, Florida, USA; H.M. Brown, Midlands Asthma and Allergy Research Association, Derby, England; C. Collins-Williams, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada; J. Kammermeyer, Iowa City Allergy Clinic, Iowa City, Iowa, USA; J.B. Mackay, Senior Chest Physician, Wellington Hospital, Wellington, New Zealand; N. Mygind, Otopathological Laboratory, Rigshospitalet, Copenhagen, Denmark; P.S. Norman, The Johns Hopkins University, School of Medicine, The Good Samaritan Hospital, Baltimore, Maryland, USA; J.M. Parkin, Chairman, Division of Otolaryngology, University of Utah, Salt Lake City, Utah, USA.
‘Syntaris’, ‘Rhinalar’, ‘Nasalide’ (Syntex).
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Pakes, G.E., Brogden, R.N., Heel, R.C. et al. Flunisolide: A Review of its Pharmacological Properties and Therapeutic Efficacy in Rhinitis. Drugs 19, 397–411 (1980). https://doi.org/10.2165/00003495-198019060-00001
- Allergic Rhinitis
- Sodium Cromoglycate
- Triamcinolone Acetonide
- Seasonal Allergic Rhinitis