Medications for Allergy

Drug Approvals

(BANM, US Adopted Name, rINNM)

Pharmacopoeias. In Europe and US.

European Pharmacopoeia, 6th ed. (Mometasone Furoate). A white or almost white powder. Practically insoluble in water slightly soluble in alcohol soluble in acetone and in dichloromethane.

The United States Pharmacopeia 31, 2008 (Mometasone Furoate). A white to off-white powder. Soluble in acetone and in dichloromethane.

Profile

Mometasone furoate is a corticosteroid used topically for its glucocorticoid activity in the treatment of various skin disorders. It is usually used as a cream, ointment, or lotion containing 0.1%.

When applied topically, particularly to large areas, when the skin is broken, or under occlusive dressings, or when given intranasally, corticosteroids may be absorbed in sufficient amounts to cause systemic effects. The effects of topical corticosteroids on the skin are described. For recommendations concerning the correct use of corticosteroids on the skin, and a rough guide to the clinical potencies of topical corticosteroids.

A nasal suspension of mometasone furoate 0.05%, as the monohydrate, is given in the treatment and prophylaxis of the symptoms of allergic rhinitis. The usual adult dose is the equivalent of 100 micrograms of mometasone furoate in each nostril once daily, increased if necessary to 200 micrograms in each nostril daily. Once symptoms are controlled a dose of 50 micrograms in each nostril daily may be effective for maintenance. In the UK, the dose for children aged between 6 and 11 years is the equivalent of 50 micrograms in each nostril once daily. In the USA, similar doses may be given to treat allergic rhinitis in children from 2 years of age.

The nasal suspension is also given for the treatment of nasal polyps in patients 18 years and older the recommended initial dose in the UK is 100 micrograms into each nostril once daily, increased after 5 to 6 weeks to twice daily if needed. In the USA the recommended initial dose is 100 micrograms in each nostril twice daily, although once daily administration may be sufficient in some patients.

Mometasone furoate is used by dry powder inhaler for the prophylaxis of asthma. Doses may differ between countries and dosage units may be expressed differently, as either the amount of drug released per actuation or the amount delivered from the mouthpiece. UK licensed product information includes an initial dose of 400 micrograms inhaled once daily in the evening for mild to moderate asthma in adults and adolescents aged 12 years and older. This may be adjusted to a maintenance dose of 200 micrograms once or twice daily. In severe asthma, an initial dose of 400 micrograms twice daily is used, then titrated to the lowest effective dose once symptoms are controlled. US doses are provided in terms of the amount of drug released per actuation (an actuation that releases 110 micrograms delivers 100 micrograms from the mouthpiece). An initial dose of 220 micrograms once daily in the evening is used in adults and adolescents, aged 12 years and older, who have been treated with inhaled therapy only (bronchodilators or corticosteroids) this may be increased to a maximum of 440 micrograms daily as a single dose or 2 divided doses. Patients receiving oral corticosteroids may be started on 440 micrograms twice daily. Children aged 4 to 11 years may be given 110 micrograms once daily in the evening, regardless of prior therapy this is the maximum recommended daily dose.

Preparations

British Pharmacopoeia 2008: Mometasone Aqueous Nasal Spray Mometasone Cream Mometasone Ointment Mometasone Scalp Application

The United States Pharmacopeia 31, 2008: Mometasone Furoate Cream Mometasone Furoate Ointment Mometasone Furoate Topical Solution.

Proprietary Preparations

Argentina: Elocon Fenisona Metason Momeplus Nasonex Novasone Uniclar

Australia:: AllerMax † Elocon Nasonex Novasone

Austria: Asmanex Elocon Elovent Nasonex

Belgium: Elocom Nasonex

Brazil: Asmanexf Elocom Nasonex Topison

Canada: Elocom Nasonex

Chile: Dermenet Dermosona Elocom Flogocort Lisoder Momelab Nasonex Rinoval Uniclar

Czech Republic: Asmanex Elocom Nasonex

Denmark: Asmanex Elocon Nasonex

Finland: Asmanex Elocon Nasonex

France: Nasonex

Germany: Asmanex Ecural Nasonex

Greece: Asmanex Bioelementa Ecelecort Elocon Elovent Esine F-Din Fremomet Makiren Metason Mofur Molken Momecort Movesan Mozeton Nasamet Nasonex Pharmecort Yperod

Hong Kong: Elomet Nasonex Topcort

Hungary: Elocom Nasonex

India: Elocon Metaspray Momate Topcort

Indonesia: Dermovel Elocon Eloskin Elox Intercon Mefurosan Mesone Mofacort Mofulex Momet Motaderm Moteson Nasonex

Ireland: Asmanex Elocon Nasonex

Israel: Elocom Nasonex

Italy: Altosone Elocon Nasonex Rinelon Uniclar

Malaysia: Elomet Momate Nasonex

Mexico: Elica Elomet Elovent Rinelon Uniclar

The Netherlands: Asmanex Elocon Elovent Nasonex

Norway: Elocon Nasonex

New Zealand: Asmanex Bronconex Elocon

Philippines: Elica Elocon Momate Nasonex Rinelon

Poland: Elocom Elosone Nasonex

Portugal: Asmanex Elocom Elomet Elovent Nasomet Prospiril

Russia: Elocom Nasonex

South Africa: Elica Elocon Nasonex Rinelon

Singapore: Elomet Nasonex

Spain: Asmanexf Elica Elocom Nasonex Rinelon

Sweden: Asmanex Elocon Nasonex

Switzerland: Asmanex Elocom Nasonex

Thailand: Elomet Nasonex Rineloir †

Turkey: Elocon M-Furo Nasonex

UK: Asmanex Elocon Nasonex

USA: Asmanex Elocon Nasonex

Venezuela: Asmanex Cortynase Dergentil Elocon Eloconex † Elomet Nasonex Uniclar

Multi-ingredient

Argentina: Elosalic †

Austria: Elosalic

Chile: Velosalic

Czech Republic: Momesalic Monsalic †

Germany: Elosalic

Hong Kong: Elosalic

India: Momate-S

Indonesia: Elosalic

Poland: Elosalic

Portugal: Monsalic

Russia: Elocom-S

South Africa: Elosalic

Sweden: Elosalic

Thailand: Elosalic †

Turkey: Elosalic

Venezuela: Elosalic

The use of intranasal corticosteroids is increasingly becoming first-line therapy for many patients with allergic rhinitis, especially those with moderate to severe symptoms or those with perennial allergic rhinitis in which nasal symptoms predominate. Intranasal corticosteroids specifically inhibit the allergic inflammatory processes that contribute to the late-phase response of nasal congestion. When used prophylactically, they can also inhibit the early-phase response to allergens. Overall, they are effective in relieving sneezing, nasal itching, rhinorrhea, and congestion.

Table 3 lists available intranasal corticosteroids, along with dosing information and comparative costs. In general, these agents are considered more cost-effective for use as monotherapy than 2nd-generation antihistamines. A recent meta-analysis found intranasal corticosteroids to be more effective than oral antihistamines in reducing nasal blockage, nasal discharge, sneezing, nasal itch, postnasal drip, and total nasal symptoms. No significant difference was detected for nasal discomfort, nasal resistance, and eye symptoms. No particular product has demonstrated clinical superiority, selection of drug should be based on factors such as response, ease of administration, cost, and formulation.

Table 3 Intranasal corticosteroids

Application site irritation (e.g., nasal irritation, burning, or sneezing after administration) is the most commonly encountered side effect. Patients complaining of local irritation may be switched to various aqueous formulations. Although rare, mucosal erosion and septal perforations have been reported with long-term use. To minimize septal irritation, patients should be instructed to direct the spray upwards and toward the lateral portion of the nose. Periodic examination of the nasal septum should be performed.

Although systemic effects from intranasal corticosteroids at recommended doses are considered minimal, there are some concerns regarding long-term exposure. Reports of posterior subcapsular cataract formation have been linked with the use of intranasal or inhaled corticosteroids; however, more recent prospective trials did not reveal evidence of posterior subcapsular cataract formation or elevation in intraocular pressure.

In 1998, the FDA’s advisory committees on pulmonary and allergy drugs and on metabolic endocrine drugs convened to assess data suggesting that intranasal corticosteroids may have an effect on growth velocity in children. Consequently, a new class labeling for pediatric use of inhaled and intranasal corticosteroids was mandated. At this time, the long-term significance of growth velocity reduction on final adult height is unknown. The FDA recommends routine monitoring of growth in pediatric patients using intranasal corticosteroids and titration to the lowest effective dose to minimize systemic risks.

Patient education is essential in ensuring proper use and compliance to intranasal corticosteroid therapy. Patients should be instructed on instillation techniques and informed about the possible delay in symptomatic response. Assessment of maximal response may require a therapeutic trial of several weeks. The drug should be administered regularly on a daily basis, rather than as needed for rescue relief.

For patients with severe disease, the combined use of intranasal corticosteroids and antihistamines may be necessary to control symptoms. The use of oral corticosteroids should be reserved for patients with severe exacerbations or intractable disease due to high risk of systemic adverse effects.

Most intranasal corticosteroids (CS) take a few days to work with the exception of the newer, more potent agents fluticasone and mometasone. Regardless, the maximum effect requires 1-2 weeks and possibly up to 3 weeks. Patients should be encouraged to contact their healthcare provider if no benefit is seen in this time. Often anti-allergy therapy is prescribed on a presumptive basis. Patients may be on intranasal CS therapy and not be aware of which allergens they are sensitive to. Skin prick allergy testing can easily assess allergy status. Once specific allergens are identified, appropriate environmental controls can be instituted.

When a patient exhibits intolerance to a specific intranasal corticosteroids product, an excipient in the formulation may be the cause. A suggested intervention would be to switch to an alternative product. For example, an alcohol-free product could be recommended over a product containing alcohol. Additional reinforcement should target instructions on proper nasal CS administration, and nasal conditioning (moisturizing). Often overlooked are patient-specific nasal behaviors. For example, a patient may be reporting nosebleeds, and through further inquiry reveals he is a frequent nose-picker; another patient may irrigate the nose with hydrogen peroxide. If nosebleeds remain problematic for the patient, referral to an Ear, Nose and Throat Specialist may be warranted. To facilitate tailoring patient therapy, Table 8 compares various intranasal corticosteroids available in the U.S.

Conclusion

Allergic rhinitis is characterized by acute and late phase reactions. Inflammation plays a dominant role in maintaining the late phase and contributes to the increased risk of complications. Intranasal steroids have been proven effective treatment for allergic rhinitis and are superior to oral antihistamines. Therefore, first-line treatment of allergic rhinitis should be intranasal steroids in patients with allergic rhinitis of perennial or seasonal pattern with persistent or moderate symptoms. Environmental control measures should target allergens relevant to the individual. Pharmacists are in a unique position to provide balanced information and take patient-specific factors into consideration when evaluating an individual patient for specific therapy for allergic rhinitis.

Intranasal corticosteroid sprays are most effective when used consistently. Some patients may not be prepared to use nasal sprays and this unfamiliarity coupled with negative preconceptions can hamper successful therapy. Both pharmacists and physicians need to educate the patient that intranasal corticosteroids work best when taken on a regular basis. Proper administration technique is very important to minimize adverse effects (bleeding and nasal septal perforation) and to optimize outcomes. The spray should target the nasal turbinates. Table 7 outlines the most important information to convey to the patient administering aqueous nasal sprays. Patient adherence is enhanced with fewer daily doses and a convenient dosing schedule. Providing written material along with verbal instruction further improves adherence. There is a growing body of published literature describing a circadian rhythm to airway biology and pathophysiology as it relates to asthma. The circadian pattern in allergic rhinitis is less clear. For now, patients should be instructed to administer the intranasal corticosteroids (CS) spray at a convenient time. However, nighttime admin-istration can worsen the dripping of the spray liquid down the back of the throat. Patients who cannot tolerate this sensation should administer the dose during the day.

Researchers are trying to identify variables that can impact patient adherence. Study models take into consideration prior experience with the class of agents, adverse effects, patient perceptions of risk and benefit, and interference with usual routines. Patients may not tolerate an individual product’s odor, taste, or sensation upon administration. There appear to be differences among the various products in this regard. In one study, several of the sensory attributes of Nasacort AQ (odorless and tasteless) were preferred over those of Flonase and Nasonex (both of which contain phenylethyl alcohol).

Patients with allergic rhinitis are at significantly greater risk for acute and chronic sinusitis. Chronic inflammation is recognized as playing a larger role in the pathophysiology of chronic sinusitis. Currently, there is no intranasal CS approved by FDA for acute therapy of sinusitis. Nevertheless, patients should be instructed to continue using their intranasal steroids while undergoing treatment for their sinusitis. Symptoms may improve more rapidly and to a greater degree with no increase in adverse events.

Patients with allergic rhinitis should be cou nseled to modify their environment to minimize exposure to relevant allergen triggers.Implementing targeted environmental control measures makes sense when the clinical signs and symptoms match allergy skin testing results. Some environmental control measures are more effective than others (baits are more effective than sprays for cockroach control). A greater challenge is the feasibility of implementing these effective measures. For example, a patient allergic to tree pollen (or any other seasonal allergen) would be best served by avoiding the outdoors and keeping outdoor air from infiltrating the indoor space. Performing such extreme measures is not likely nor necessary given available treatments. Protective facemasks may be effective when the grass/tree allergic patient needs to be outside for long periods (doing yard work). Keeping windows closed and using air conditioning in the spring/summer can substantially reduce indoor allergen exposure and provide symptom relief. Perennial allergies to indoor allergens pose greater challenges to avoidance than outdoor allergens. Common allergens inside the home include dust mites, cockroaches, pet dander (cats/dogs/hamsters), and mold.

Practical and likely to be beneficial environmental control measures are detailed in Table 6. Website addresses are provided to guide the reader to additional resources. Some strategies may have a beneficial impact on more than one allergen. For example, controlling indoor moisture can help reduce dust mite, cockroach, and mold allergen burden. Cockroach antigen remains present after extermination and cleaning with warm bleach-water solution removes this residue. Combined strategies (pharmacologic, environmental, and behavioral) are more likely to be successful against any specific allergen than single interventions.

Rhinitis can be caused by nonallergic stimuli. Differentiating allergic rhinitis from these often more serious causes is important. Allergic rhinitis is often misdiagnosed as a viral rhinitis, perhaps due to the similar clinical presentation.Other etiologies of rhinitis exist that can be differentiated from one another (Table 5). A successful treatment plan must include patient/provider education, relevant nonpharmacologic modalities and drug therapy.

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Overall, intranasal CSs are well tolerated, even by children. All intranasal corticosteroids are currently pregnancy category C. Although budesonide oral inhaler (Pulmicort) is pregnancy category B, budesonide nasal spray remains category C. The side effect profile of these agents derives from clinical studies as reported adverse events, and published case reports. Table 3 lists the most common reactions. The most serious effects that would impact continuing therapy are nose bleeding and nasal septal perforation.

Topical administration of intranasal corticosteroids (CS) does not necessarily translate into a lack of systemic availability or risk of systemic effects. Table 4 lists pharmacokinetic parameters of select intranasal corticosteroids. The newer agents, fluticasone propionate and mometasone furoate, have lower bioavailabilities. Mometasone has the lowest systemic availability with fluticasone following closely. However, differences in bioavailability have not translated well into differing systemic effects. In general, all intranasal corticosteroids have been demonstrated to be safe at FDA recommended dosages.

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Any exogenous glucocorticoid in the body will cause less endogenous glucocorticoid production. In turn, measurements of basal hypothalamic-pituitary-adrenal (HPA) activity provide the most sensitive indication of systemic exposure to intranasal CS. However, presence of exogenous glucocorticoid does not absolutely translate into an increased risk of altered physiologic systems. Such overly sensitive markers include urinary-free cortisol excretion and area-under-the-curve cortisol concentration. To determine whether the bioavailability of intranasal corticosteroids is having an adverse clinical impact, other testing procedures are warranted. The adrenocorticotropic hormone (ACTH) stimulation test has better predictive value than previously mentioned tests of HPA-axis function. Studies that examined various intranasal CS (beclomethasone, budesonide, fluticasone, mometasone, and triamcinolone) showed no significant effect on basal HPA-axis function.

In children, intranasal corticosteroids maintain their efficacy but are associated with concerns of possible effects on growth velocity. As with inhaled corticosteroids, study design was directed on the younger prepubertal child. In a placebo-controlled trial (n=100, age 6 to 9.5 years), beclomethasone was shown to impair growth velocity to a statistically significant degree (0.9 cm over 1 year of treatment). However, as with inhaled corticosteroids, this may appear to be a drug-specific phenomenon. Mometasone furoate (highly potent and extensively cleared compound) has been studied in young children and did not have any adverse impact on their growth rate. These findings are in keeping with studies in asthma using the newer agents that show no sustained effects and ultimate attainment of expected adult height. The FDA is currently in the midst of drafting a document to provide guidance in the design, conduct, and evaluation of clinical studies to assess the effects of intranasal corticosteroids on linear growth. Until more studies are published and study design issues resolved,when using intranasal corticosteroids in children it may be prudent to use the lowest effective dose and monitor growth (especially in high-risk children). Children with concurrent asthma and treated with orally inhaled corticosteroids may be at highest risk.

All aqueous intranasal CS preparations contain preservatives. Benzalkonium chloride is the preservative of choice for beclomethasone, flunisolide, fluticasone, mometasone and triamcinolone. Budesonide contains potassium sorbate as the preservative. In vitro, benzalkonium chloride has cytotoxic effects on epithelium and damages ciliary motility. Klossek et al.evaluated the 6-month treatment effect of Nasacort AQ (aqueous triamcinolone with benzalkonium as preservative) 220 mcg/day in subjects with perennial allergic rhinitis. Nasal biopsies were performed before and after treatment. The study determined that sustained treatment with intranasal triamcinolone did not lead to atrophy of the nasal mucosa or impairment of mucociliary function. In another report, the alcohol component was implicated in slowing ciliary motility. These authors recommend alcohol-free formulations, especially for chronic use. The clinical relevance of this potential adverse effect is likely to be insignificant. Overall, except for the possibility of intranasal beclomethasone, the intranasal corticosteroids have a good safety profile and are well-tolerated.

Intranasal corticosteroids (CS) can prevent symptoms of seasonal allergic rhinitis when initiated prior to the start of the allergy season. In patients with mild intermittent symptoms, oral or intranasal antihistamines provide adequate relief and would remain recommended as first line in this population. Once symptoms become more persistent and bother the patient moderately or greater, intranasal steroids should be prescribed. More recent data suggest the ability of newer potent intranasal CS to achieve onset of clinical benefit comparable to oral antihistamines. Clinical evidence supporting this is provided by a study conducted by Kaszuba et al.In this open-label study, 88 patients with documented clinical ragweed allergy (skin prick positive and symptoms during ragweed season for the previous 2 seasons) were evaluated. Patients were randomized to receive either 2 sprays fluticasone in each nostril once daily or 10 mg loratadine once daily when bothersome symptoms occurred.

Of the 28 potential days patients could take their assigned medication, both groups used their medication for similar durations (17 days in the fluticasone group and 18 days in the loratadine group, p-value not significant). By week 2 (differences detected by day 5) and week 4, patients who took intranasal fluticasone had significantly fewer symptoms and improved quality of life, respectively. In addition, eosinophil counts and eosinophilic cationic protein levels were both significantly decreased compared to loratadine. The rationale for periodic fluticasone use is through fluticasone’s ability to suppress early the inflammatory cells and subsequent activation of the late phase when the patient is exposed to further antigen. However, until more studies are published in support of intermittent use of intranasal corticosteroids, patients should be instructed to use intranasal CS continuously during their allergy season.

The superiority of intranasal steroids over oral antihistamines is reported in a meta-analysis of 16 randomized controlled trials involving 2,267 subjects (mean age 32 years, range 12-75 years) with allergic rhinitis. Studies were excluded if they evaluated nonclinical outcomes such as in vitro results of inflammatory mediators. The intranasal CS used in these studies included beclomethasone, budesonide, fluticasone, and triamcinolone. Oral antihistamines were astemizole, cetirizine, dexchlorpheniramine, loratadine, and terfenadine. Using a fixed effects model, intranasal steroids were significantly better in providing relief in the domains of nasal blockage, postnasal drip, sneezing, and nasal itch. With respect to ocular symptoms, there were no differences between the intranasal steroid and oral antihistamines. The study reported more heterogeneity in the data for the ocular symptoms, highlighting the variability in allergic rhinitis disease expression and the requirement to tailor therapy to individual patients.

More recently, Rinne and colleagues revisited this issue, comparing a newer potent intranasal steroid (budesonide 280 mcg/day) to cetirizine 10 mg qd – a second-generation oral antihistamine considered the most potent and effective of the oral antihistamines. This study is important because it was published after the meta-analysis and contains methodology similar to published asthma studies. Newly diagnosed patients (n=143, 60% diagnosed <2 years) were randomized in a blinded fashion to either budesonide or cetirizine for one year of continuous treatment. A protocol was established to treat patients with intolerable breakthrough symptoms in a step-wise fashion. A unique aspect of this trial was an additional 12-month open-label extension; this phase sought to determine when patients experienced their first relapse after discontinuing therapy. Table 2 summarizes the clinical outcomes of this comparison. There were no significant differences in the occurrence of adverse effects between the two groups. This study concluded that intranasal budesonide is more effective than cetirizine for the long-term treatment of allergic rhinitis.

Allergic rhinitis deserves attention due to its high prevalence in adults and children along with significant associated morbidity. Allergic rhinitis is classified in two main categories: seasonal and perennial. Patients with the seasonal form exhibit acute symptoms during the times of year when pollens are released from trees (early spring), grasses (late spring/early summer), and other plants such as ragweed (late summer and fall). The perennial form includes allergens that are present all year round (animal dander, dust mites, and cockroaches).

The combined (direct and indirect) costs of managing allergic rhinitis have been estimated to range from $3.25 to $8 billion every year. The direct costs include visits to the physician, laboratory testing, medications, and the costs of treating the complications. The indirect costs include loss of income due to absenteeism and costs to businesses from reduced productivity at work.

Allergic rhinitis has been regarded as an annoying disease and the associated complications underappreciated. The untreated inflammatory process in the nose can result in socially embarrassing features, such as the “allergic salute” (running the palm of the hand upward across the nose, leading to a crease across the bridge of the nose), as well as medically significant complications such as asthma, sinusitis, otitis media with effusion, or the development of nasal polyps. Other potential consequences of undertreated allergic rhinitis can include irritability, fatigue, lethargy, poor concentration, and poor self-image.

Patients entering a pharmacy are confronted with a plethora of over-the-counter agents to treat their symptoms. Direct-to-consumer advertising may add to this overwhelming milieu. In 1999, the pharmaceutical industry spent $226 million advertising antihistamines and $114 million advertising intranasal corticosteroids (CS) directly to patients. This accounts for nearly 6% of antihistamine sales and 12% of nasal CS sales. Healthcare providers are equally overwhelmed with the choices of legend drugs available and the pressures they bear from pharmaceutical industry sales representatives. This article will discuss the use of aqueous nasal corticosteroids for the management of allergic rhinitis and emphasize practical issues in their use.

Linking Nasal Inflammation with Clinical Presentation

Patients with allergic rhinitis are believed to have a genetic predisposition for the development of Immunoglobulin E (IgE) antibodies against specific molecules (allergens). The process begins with repeated exposure to the allergen causing a sensitization or priming of the immune system. The immune system is now poised to respond using a complex array of cells and cytokines to initiate the allergic response. Allergic rhinitis is the clinical disease expression of this sensitivity characterized by an acute-phase response and late-phase response.

The acute-phase response is triggered when the allergen interacts with IgE molecules bound to mast cells. There are more mast cells in the noses of allergic individuals than in nonallergic individuals. Mast cells become activated and release preformed mediators of which histamine is the most well known. Accompanying histamine are mediators that are newly synthesized as a result of the allergen-antibody interaction. These synthesized mediators are the products of arachidonic acid metabolism (involving the cyclooxygenase and 5-lipoxygenase enzyme systems) and include potent proinflammatory molecules such as prostaglandins (PG), leukotrienes, and various interleukins. Both groups of preformed and newly synthesized mediators are responsible for the clinical manifestations of allergic rhinitis.

The clinical manifestation of the acute-phase relies on the faster acting of the mediators. Histamine is the primary mediator involved. Approximately half of the symptoms of allergic rhinitis can be attributed to histamine. Clinical manifestations of histamine depend on the binding location within the nose. The nasal turbinates are the target tissue for the allergic cascade. The turbinates are soft tissue appendages inside the nose that help filter and humidify inspired air. When histamine occupies endothelial cells of postcapillary venules, the result is increased vascular permeability leading to mucosal edema (of the turbinates), feelings of congestion, and watery rhinorrhea. Histamine causes itching and sneezing when it binds to nociceptive neurons. These symptoms can often be controlled by H1-antihistamines. Older generations of antihistamines (diphenhydramine and chlorpheniramine) have been notorious for their sedative and drying effects, making patient acceptance low in an era of newer, less sedating antihistamines (fexofenadine and loratadine). The chronic inflammatory process sustains persistent patient symptoms including nasal blockage. In this phase, only a partial response is achieved with antihistamines.The newly formed mediators (PG and leukotrienes) contribute to nasal congestion, rhinorrhea, and edema.

The late-phase reaction is responsible for the ongoing clinical symptoms suffered by the patient. It involves the recruitment of a new host of chemo-attractants, proinflammatory cells (eosinophils) and their highly cytotoxic mediators (major basic protein, eosinophil cationic protein, IL-5, etc). Symptoms in the late phase tend to be similar to those experienced in the acute phase, predominately nasal congestion. The complications of allergic rhinitis are often the result of undertreated chronic mucosal inflammation. To improve symptoms and reduce long-term complications, treatments should target the underlying inflammation.

Topical nasal corticosteroids (CS) gain entry into the cell cytoplasm and interact with the glucocorticoid receptor (GR). The CS/GR complex undergoes a conformational change, becoming active, prior to entering the cell nucleus. Gene expression is hypothesized to be a principal mechanism of altering the inflammatory state. The direct effects may be a reduction in the cytokine-induced production of pro-inflammatory mediators. Whether the interaction has activating or repressive effects may be dependent on the gene being modified. The clinical benefits observed with CS can be attributed to the wide-ranging suppressive effects on the immune system, and anti-inflammatory mediator production. This article will further discuss these clinical benefits by summarizing representative clinical studies evaluating nasal corticosteroids in allergic rhinitis.

The cellular and biochemical effects of glucocorticoids are immediate, but varying times are required to produce a clinical response from corticosteroids. After exposure to the allergic trigger, rhinitis symptoms have a rapid onset, often within minutes. Treatment needs to take effect as quickly, or better still, prevent symptoms from occurring. The traditionally held view was that the onset of clinical effect from intranasal CS was delayed by several days. More recent evidence contradicts this and suggests a quicker onset in benefit. Consequently, most patients’ symptoms will improve within the first 1-2 days of therapy and reach maximum improvement in 1-2 weeks. This is explained by the ability of corticosteroids to attenuate both the acute phase and late phase of the allergic reaction. Nasal challenge studies show a marked decrease in symptoms and inflammatory cells and their products. The clinical presentation of allergic rhinitis is patient-specific and there is variability in how patients present. Table 1 lists the various signs and symptoms of allergic rhinitis, although not all patients will express all symptoms.