Intranasal corticosteroids for allergic rhinitis

May 2002

Intranasal corticosteroids are effective for controlling symptoms of seasonal and perennial allergic rhinitis. They adequately control the symptoms of itch and sneeze, nasal discharge and nasal blockage. Six intranasal steroids are available in numerous products and strengths.

Pharmacology and efficacy

Intranasal steroids have been described as the most effective medication class for controlling allergic rhinitis symptoms by the Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology (Diagnosis and Management of Rhinitis: Parameter Documents). Six agents are available: beclomethasone dipropionate, flunisolide (Nasalide, Elan), triamcinolone acetonide, budesonide (Rhinocort, AstraZeneca), fluticasone propionate (Flonase, GlaxoSmithKline) and mometasone furoate (Nasonex, Schering). Numerous studies have evaluated the intranasal steroids. These studies generally have been short and have included subjects with moderately severe symptoms. Most studies have not found differences among the agents, and the available intranasal steroids are generally considered to be equally effective. Intranasal steroids are most effective if used prior to allergen exposure.

Pharmacological effect and potency of the intranasal steroids can be assessed by several means. Cutaneous vasoconstriction is a common method of rating corticosteroid potency. Lipophilicity, receptor-binding affinity and cytokine inhibition have also been used to assess relative pharmacologic potencies of the intranasal steroids.

Differences in potency from these methods have been detected among the intranasal steroids, and rankings have been published. In general, mometasone furoate, fluticasone propionate and budesonide have been rated as most potent. However, it is important to consider that the relationship between these rankings of potency and their clinical anti-inflammatory effects or clinical efficacy has not been determined, and may not be clinically relevant.

The pharmacokinetic profiles of the intranasal steroids are also important to consider. Systemic absorption of the intranasal steroids may occur orally (for a large proportion of a nasally administered dose is swallowed) or through the nasal mucosa. The intranasal steroids listed above undergo significant first-pass hepatic metabolism — when swallowed, the drug is absorbed through the gastrointestinal tract. Nasal absorption probably accounts for most of the drug reaching the systemic circulation. Systemic bioavailabilities have not been well characterized for all of the intranasal steroids.

The limited data available from product labeling indicate that flunisolide and budesonide achieve greater systemic bioavailability than fluticasone propionate or mometasone furoate. How this information relates to the pediatric population and its clinical significance has not been determined.

Adverse effects

The intranasal steroids are generally well tolerated when used appropriately. Proper technique of use is important to follow to minimize adverse effects. Patients complaining of adverse effects or lack of efficacy should be evaluated for administration technique. The most common adverse effects include epistaxis, nasal dryness, stinging, irritation, or burning. Some patients may prefer one agent over another because of these effects, as well as other various reasons (see Patient Acceptance below).

The adverse effect probably most concerning to prescribers and patients is the potential for growth inhibitory effects. Product labeling for the intranasal steroids includes information that these agents may cause a reduction in growth velocity.

The long-term effects of this on final adult height are unknown. Numerous studies have been published which have evaluated the potential growth inhibitory effects of the intranasal steroids. When assessing these studies it is important to consider that growth is a complex and dynamic process, occurring in various phases. Relatively short-term studies completed in one age group may not be comparable to other age groups. Correlations between data from short-term (six months or less) or intermediate-term studies (greater than six months, without assessment on final adult height) and long-term growth velocities are not strong. Growth velocity over a three- to four-year period in childhood affects 34%-38% of final height variation. For normal prepubertal children, only weak correlations between two consecutive annual growth velocity measurements exist.

Several intermediate-length studies have been published and these studies are the basis for the product labeling describing the potential for growth inhibition of intranasal steroids. Beclomethasone dipropionate (168 µg BID) was compared with placebo in a double-blind, randomized manner in 100 children (6-9 years of age) with perennial allergic rhinitis for one year (Skoner). The beclomethasone dipropionate dose used is the highest recommended dose in the product’s labeling. The rate of change of standing height was the primary safety parameter, and height was measured with a stadiometer seven times throughout the study.

Ninety subjects completed the study. Treatment groups differed at baseline in age and height (greater in treatment group). Statistical analysis was used to normalize baseline differences in height. The results indicated that growth rates were less with beclomethasone diproprionate than with placebo - 5.0 cm change in height over one year vs. 5.9 cm, respectively (p values not given). The hypothalamic-pituitary-adrenocortical (HPA) axis was also evaluated by measuring morning basal cortisol concentrations and responses to cosyntropin stimulation. No differences were found with this measurement between the 2 groups. The authors concluded that the data suggest that nasally administered beclomethasone dipropionate may slow growth rate in children, although effects upon adult height are unknown.

In a similar study, mometasone furoate (100 µg/day) was compared with placebo in a double-blind, randomized trial for one year (Schenkel). Eighty-two children (3-9 years of age) with perennial allergic rhinitis completed the study and were comparable at baseline. Height was measured six times by stadiometry throughout the study and change in height was the primary safety parameter. HPA axis function was assessed by cosyntropin stimulation testing. It was found that the rate of growth was similar for both groups throughout the study. No adverse effects upon the HPA axis were found.

The most valuable data relating to the potential for growth suppression with use of intranasal steroids are long-term studies where final adult height is determined. Unfortunately, these studies do not exist. However, studies evaluating long-term treatment with orally inhaled corticosteroids have been published. Two hundred and eleven children with asthma were followed (mean treatment duration of 9.2 years) until final height was attained (Agertoft). Of these, 142 children were treated with a mean daily budesonide dose of 412 µg, and were compared with controls and healthy siblings. While some reduction in growth velocity occurred early on in the first year in patients receiving budesonide, targeted adult heights were obtained. Another study evaluated the effects of budesonide (400 µg/day) as compared with nedocromil or placebo in more than 1,000 children (5-12 years of age) for four to six years (Childhood Asthma Management Program Research Group). Final adult heights were estimated, and it was found that children treated with budesonide grew 1.1 cm less than the placebo group (p < 0.05). This reduction, however, mostly occurred in the first year of treatment. Growth rates by the end of treatment did not differ, and projected final adult heights were similar among all treatment groups.

Product patient acceptance

Because there does not appear to be clear differences among the intranasal steroids in efficacy or safety, patient acceptance may be important to consider. Factors that may contribute to acceptance and use of a product include odor, taste, aftertaste, run off into the nose or throat, delivery device and common adverse effects. Some published data exist from studies that have evaluated tolerability and patient preferences for specific intranasal steroids. These data are hampered by lack of a standardized patient acceptance tool; as well, questionable statistical analysis techniques have been used for some studies. Much of these data were derived from adults, and may not be applicable to children.

It may be possible that patients prefer an intranasal steroid with no odor or aftertaste, as one study indicated. Most patients would probably prefer a product which does not “run down” the throat. One double-blinded study compared triamcinolone acetonide, fluticasone propionate and beclomethasone diproprionate for acceptability and sensory perceptions in 95 adults using a 13-point questionnaire. Triamcinolone acetonide was rated better for comfort as compared with mometasone furoate, although more patients also rated triamcinolone acetonide as having more run-off than mometasone furoate and fluticasone propionate.

The numerous intranasal steroid products are available in differing strengths and aerosol or aqueous dosage forms (see Table). It is believed that intranasal distribution of the corticosteroid is improved with aqueous dosage forms as compared with aerosols. A clinical benefit of this, however, has not been shown. Most products are available in both dosage forms.

The six different intranasal steroids are generally considered to be equally efficacious in the treatment of allergic rhinitis. Recently published practice guidelines indicate the intranasal steroids are the most effective pharmacotherapy for controlling symptoms of allergic rhinitis. Although the available intranasal steroids differ in pharmacologic potency and pharmacokinetic variables, such as systemic absorption, how these differences may translate to clinically important effects is not known. The intranasal steroids products may also differ in patient acceptance factors, although these differences have not been well studied, and their applicability to the pediatric population has not been defined. The potential adverse effects of the intranasal steroids upon growth in children are not well defined, and require additional study. Although some controlled studies suggest that treatment with intranasal steroids for one year may adversely affect growth, how this growth suppression may affect final adult height, if at all, has not been determined. As well, it is believed that growth determination studies of one year do not strongly correlate with long-term growth potential. Data from long-term controlled trials using orally inhaled corticosteroids in children with asthma have shown that while inhaled corticosteroids may suppress growth transiently early in therapy, final adult height does not appear to be altered. Taken together, this information should be encouraging to clinicians and patients.

It is still wise, however, to monitor growth of patients using intranasal steroids, and to use the lowest possible dose to control symptoms. When prescribed, it is also important to adequately instruct patients on intranasal steroids about the proper administration technique, to minimize local adverse effects and to improve compliance.

For more information:

• Dykewics MS, Fineman S, ed. Diagnosis and management of rhinitis: parameter documents of the joint task force on practice parameters in allergy, asthma and immunology. Ann Allergy Asthma Immunol. 1998;81(Part II):506.
• Corren J. Intranasal corticosteroids for allergic rhinitis: how do different agents compare? J Allergy Clin Immunol. 1999;104:S144-9.
• Pedersen S. Assessing the effect of INS on growth. J Allergy Clin Immunol. 2001;108:S40-4.
• Szefler SJ. Pharmacokinetics of intranasal corticosteroids. J Allergy Clin Immunol. 2001;108:S26-31.
• Schenkel EJ. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics. 2000;105:e22.
• Skoner DP. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics. 2000;105:e23.
• Bachert C. Patient preference and sensory comparisons of three nasal steroids: triamcinolone acetonide aqueous nasal spray, fluticasone proprionate and mometasone furoate. Allergy. 2000;55(suppl 63):197.
• Agertoft L. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000;343:1064-1069.
• The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedcromil in children with asthma. N Engl J Med. 2000;343:1054-1063.