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By Sis Ueng, PharmD Candidate
College of Pharmacy University of Texas
Barry Browne, PharmD
Coordinator of Drug Information
Scott and White Hospital and Health Plan
Intranasal corticosteroids are used to treat and prevent the symptoms of allergic rhinitis. Although typically not a life-threatening disease, the symptoms of allergic rhinitis clearly interrupt daily life activities. Approximately 8% of the population exhibits symptoms of allergic rhinitis.1
Intranasal corticosteroids modulate allergic rhinitis symptoms in both the early and late stages of inflammatory response to an allergen; the agents block the synthesis and release of inflammatory mediators (e.g., histamine, kinin, leukotriene, prostaglandin) involved in the early response phase. During the late response phase, intranasal corticosteroids decrease epithelial permeability, decrease inflammatory mediator production, decrease the secretory response to the allergen, and decrease the number of inflammatory cells (e.g., basophils, neutrophils, eosinophils) that migrate into the nasal mucosa.2,3
The intranasal corticosteroids approved by the U.S. Food and Drug Administration for the treatment and prevention of allergic rhinitis are flunisolide (Nasalide, Nasarel; Dura), beclomethasone dipropionate (Beconase, Beconase AQ; GlaxoSmithKline; Vancenase, Vancenase Pockethaler, Vancenase AQ 84 mg; Schering-Plough), triamcinolone acetonide (Nasacort, Nasacort AQ; Aventis; Tri-Nasal; Muro), budesonide (Rhinocort, Rhinocort Aqua; AstraZeneca), fluticasone propionate (Flonase; GlaxoSmithKline), and mometasone furoate monohydrate (Nasonex, Schering-Plough).4,5,6
Absorption: Lipid solubility determines the rapidity of absorption of an agent by the nasal mucosa. As lipophilicity increases, the rate of absorption increases. In addition to changes in absorption, increased lipophilicity for intranasal corticosteroids appears to increase retention in the nasal mucosa, produces greater ability to reach glucocorticoid receptors, and allows increased length of binding to glucocorticoid receptors. From highest to lowest, the ranked order of lipid solubility for intranasal corticosteroids is mometasone furoate, fluticasone propionate, beclomethasone diproprionate, budesonide, triamcinolone acetonide, and flunisolide. Intranasal corticosteroids can be absorbed and enter the systemic circulation via the nasal and gastrointestinal system.7
Approximately 80% of the intranasal corticosteroid dose is swallowed after administration. The corticosteroid passes through the gastrointestinal system and is subsequently absorbed. No information is available on nasal absorption of intranasal corticosteroids from the nasal mucosa.3 The systemic bioavailabilities of each intranasal corticosteroid via the gastrointestinal system is as follows:8
One factor that may potentially interfere with the absorption of the intranasal corticosteroid in the nasal mucosa is nasal congestion. Two suggestions to clear the nasal blockage are to blow the nose or administer a topical nasal decongestant five to ten minutes prior to administering the intranasal corticosteroid, although use of topical nasal decongestants is controversial.4
Distribution: Distribution of intranasal corticosteroids within areas of the body has not been described.9,10
Metabolism: Intranasal corticosteroids are metabolized in the liver. In addition to liver metabolism, beclomethasone dipropionate is metabolized in the lungs and triamcinolone acetonide is metabolized in the kidneys.4,5,10
Elimination: Beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide are renally excreted. In addition to urinary excretion, beclomethasone dipropionate and fluticasone also exhibit fecal elimination. Mometasone furoate is eliminated primarily via the bile and, to some extent, in the urine.4,10
Potency: Intranasal corticosteroids with greater lipophilicity are more potent. From highest to lowest, the ranked order of potency is mometasone furoate, fluticasone propionate, budesonide, and triamcinolone acetonide. The potency ranked order corresponds with the ranked order for lipophilicity.8 However, potency is not directly related to clinical efficacy or effectiveness.
Onset of action: Each intranasal corticosteroid has a different onset of action. The onsets of action range from 12 hours to days. Patients can receive some symptom relief within a matter of hours with certain intranasal corticosteroids, but to attain maximum relief, patients should use the intranasal corticosteroids for several days.4,8 The onset of action of each intranasal corticosteroid is as follows:8
Efficacy: Lumry8 found no clinically significant difference in efficacy between the different intranasal corticosteroids. All of the available agents were shown to be effective in reducing nasal blockage or congestion, nasal itching, sneezing, and rhinorrhea. Even though the intranasal corticosteroids appear to be equal in efficacy, some of the agents require more per-nasal administrations than others because of differences in lipophilicity and potency profiles.
Several clinical studies have compared different intranasal corticosteroids, but no single trial is available comparing all the intranasal corticosteroids as a group. Results of several clinical studies comparing clinical efficacy between a variety of the agents are shown here.8
Efficacy in seasonal allergic rhinitis:
Fluticasone propionate (200 mg/day) =
Efficacy in prophylaxis for seasonal allergic rhinitis (administered for eight weeks):
Mometasone furoate (200 mg/day) =
Efficacy in perennial rhinitis:
Fluticasone propionate (200 mg/day)³ > beclomethasone dipropionate (200 mg BID);
Mometasone furoate (200 mg/day) =
Dosing is variable for the agents; refer to specific product monographs for dosing guidelines.
Some of the intranasal corticosteroids are available in different formulations: aqueous or aerosolized (dry). The intranasal corticosteroids available in an aqueous formulation are Beconase AQ, Vancenase AQ 84 mg, Nasalide, Nasarel, Nasacort AQ, Tri-Nasal, Nasonex, Rhinocort Aqua, and Flonase. Intranasal corticosteroids available in the aerosolized formulation are Beconase, Vancenase Pockethaler, Nasacort, and Rhinocort.4,6,11 Nasal irritation is more often associated with aerosolized formulations, possibly due to spray volume or force or propellant.12 All of the aqueous formulations contain benzalkonium chloride as a propellant, except for Nasonex, Rhinocort Aqua, and Rhinocort.8,11
Drug interactions have not been reported with intranasal corticosteroids. Caution should still be exerted when administrating intranasal corticosteroids with other medications because intranasal corticosteroids can be systemically absorbed.4,13
Pregnancy and lactation:
All the intranasal corticosteroids are pregnancy category C. No data are available to indicate whether intranasal corticosteroids are excreted in breast milk with the exception of budesonide. Budesonide is considered safe for breast-feeding mothers.5,10,14
Common adverse effects of intranasal corticosteroids are nasal irritation, nasal dryness, nasal burning, sneezing, and epistaxis.4 A potential concern with chronic use of intranasal corticosteroids is the effect of the agents on mucosal histology. However, studies with budesonide, fluticasone propionate, beclomethasone dipropionate, triamcinolone acetonide, and mometasone furoate did not indicate histologic changes in the nasal mucosa after long-term use.7,8,15 One long-term study of mometasone furoate suggested that mometasone furoate could potentially reverse some allergy-related histologic changes in the nasal mucosa because of reduction in the extent of inflammatory cell migration into the nasal mucosa.8 Even though clinical studies indicate no nasal mucosal changes with long-term administration of intranasal corticosteroids, patients on long-term therapy should still have periodic examinations of the nasal mucosa.15
Another possible concern with administration of intranasal corticosteroids is hypothalamic- pituitary adrenal (HPA) axis suppression. Several studies in adults evaluating the potential of intranasal corticosteroids to produce HPA axis suppression indicated no overall clinically significant effect. A 5.5 year-long study evaluating the long-term safety of budesonide found no HPA axis suppression. Doses of 200 mg/day and 400 mg/day were evaluated in the study.16 A four-week study with fluticasone propionate at 200 mg/day and 400 mg/day twice a day found no HPA axis suppression when compared to placebo, but the 400 mg twice a day dose did result in reduced morning plasma cortisol concentrations.17 Other clinical studies have evaluated intranasal corticosteroid effect on the HPA axis; results were conflicting. Some evaluations reported reduced cortisol concentrations and others did not. The two main factors that appear to contribute to development of HPA axis suppression are dose and duration of treatment.18
Conflicting data are also present regarding possible effects of intranasal corticosteroids on growth velocity and the HPA axis in children. Skoner et al19 evaluated the effect of beclomethasone dipropionate (BDP) on growth velocity in children ages six to nine years old for one year. The dose evaluated was 168 mg twice a day. Results of the study indicated that children who used BDP had a decrease in growth rate when compared to the placebo group, but no difference in cortisol levels were observed for the subjects in either group. Meltzer et al20 performed a dosing range study with mometasone furoate in children ranging from five to eleven years old over a four-week period. Doses of 25 mg, 100 mg, and 200 mg were evaluated, as well as 168 mg/day of BDP. No significant changes in HPA axis function were found after four weeks of treatment in 130 patients.20 No information is available to determine the possible effect of intranasal corticosteroids on final growth height in children.19
Less common adverse effects of intranasal corticosteroids are Candida infections and septal perforations. Septal perforations can occur when patients direct the spray towards the septum rather than the inferior turbinate.7
Cataract development has been associated with both inhaled and oral corticosteroids. The Blue Mountain Eyes Study, reported in the New England Journal of Medicine in 1997, did not find a definite cause and effect relationship between inhaled corticosteroids and cataract development, but the investigators indicated that an association does appear to exist.21 Chylac,22 in an accompanying editorial, commented that the risk of posterior subcapsular cataract development associated with intranasal corticosteroid use may actually have been underestimated by the design of the Blue Mountain study. Additionally, the potential development of ocular adverse events has not been established for each corticosteroid; therefore, no data exist regarding risks with each individual agent.23
Oral antihistamines comparison:
Weiner et al24 reviewed available clinical trials comparing intranasal corticosteroids to oral antihistamines in allergic rhinitis. Included in the evaluation were beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. The results of the meta-analysis of 16 randomized, controlled trials indicated that intranasal corticosteroids were more effective than oral antihistamines in relieving nasal blockage, nasal discharge, nasal itch, and postnasal drip.
Stempel and Thomas25 evaluated 13 randomized, double-blind clinical trials comparing intranasal corticosteroids and oral nonsedating antihistamines. The intranasal corticosteroids evaluated were beclomethasone dipropionate, budesonide, fluticasone propionate, flunisolide, mometasone acetonide, and triamcinolone acetonide. Results indicated that intranasal corticosteroids were statistically superior to oral nonsedating antihistamines for relieving stuffy nose and improving overall nasal symptoms.
Leukotriene receptor antagonist comparison;
Pullerits et al26 compared beclomethasone dipropionate to zafirlukast (Accolate), the leukotriene receptor antagonist. The purpose of the study was to determine if zafirlukast could attenuate the symptoms of allergic rhinitis by antagonizing leukotriene effects in the nasal mucosa. Zafirlukast was not shown to provide benefit with symptoms of sneezing, rhinorrhea, nasal itch, or nasal blockage, while beclomethasone showed statistically significant symptom improvement of nasal symptoms by day 20 of the 50-day trial (zafirlukast is not indicated in the treatment or prevention of allergic rhinitis).
Intranasal cromolyn sodium comparison:
Bousquet et al27 compared fluticasone propionate to disodium cromoglycate (i.e., cromolyn sodium) in the prevention of allergic rhinitis symptoms. Cromolyn sodium (Nasalcrom) is indicated in the treatment and prevention of symptoms of allergic rhinitis. Fluticasone propionate showed greater improvement in preventing nasal blockage, nasal discharge, sneezing, and nasal itch when compared to cromolyn sodium. Compliance was evaluated in the study, since cromolyn sodium requires four times a day administration, but the difference in compliance between the two treatments groups was not statistically significant.
Intranasal antihistamine comparison:
Berlin et al28 compared flunisolide (Nasarel) to azelastine (Astelin) to determine effectiveness in controlling allergic rhinitis symptoms. The results indicated that flunisolide was more effective in controlling symptoms of nasal congestion and sneezing, while azelastine was more effective in controlling symptoms of rhinorrhea.
In general, the intranasal corticosteroids range in cost from $30-$50/month, based on the average wholesale price (AWP). AWP for each of the intranasal corticosteroids available on the market is show below:29
Allergic rhinitis can cause a decrease in productivity and absenteeism from work or school because of the significant symptomatology associated with the disease.25 Intranasal corticosteroids have been shown to provide symptomatic control (e.g., nasal blockage, rhinorrhea, itching), as well as modifying the underlying disease process. No difference exists in effectiveness between the different intranasal corticosteroids. As a result, cost, convenience of administration, and age indication can help provide a basis for formulary decisions.
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16. Pipkorn U, et al. Long-term safety of budesonide nasal steroid: a 5.5-year follow-up study. Clinical Allergy 1988; 18:253-9.
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19. Skoner DP, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics. www.pediatrics.org. 2000 Feb; 105(2): e23.
20. Melter EO, et al. A dose-ranging study of mometasone furoate aqueous nasal spray in children with seasonal allergic rhinitis. J Allergy Clin Immunol 1999 Jul; 104(1):107-14.
21. Cumming RG, et al. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997; 337(1):8-14.
22. Chylack LT. Cataracts and inhaled corticosteroids. Editorial. N Engl J Med 1997; 337(1):46-8.
23. Cumming RG, Mitchell P. Inhaled corticosteroids and cataract. Drug Safety Jan 1999; 20(1):77-84.
24. Weiner JM, et al. Intranasal corticosteroids vs. oral H1 receptor antagonists in allergic rhinitis: systematic review of randomized controlled trials. BMJ 12 Dec 1998; 317:1624-9.
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27. Bosquet J, et al. Prevention of pollen rhinitis symptoms: comparison of fluticasone propionate aqueous nasal spray and disodium cromoglycate aqueous nasal spray. Allergy 1993; 48:327-33.
28. Berlin JM, et al. Efficacy of a steroid nasal spray compared with an antihistamine nasal spray in the treatment of perennial allergic rhinitis. JAOA 2000 Jul; 100(7):S8-S13.
29. First DataBank Price-Check PC. Vers. 3.07. Jan 2001. First DataBank Inc. 19 Jan 2001.