AHFS Class:

• Corticosteroids 52:08.08

Generic Name(s):

• Fluticasone Propionate

Fluticasone propionate is a synthetic trifluorinated corticosteroid.1,2,3,6,7,8,26,48,65,66

Fluticasone propionate nasal spray is used for symptomatic treatment of seasonal or perennial allergic rhinitis and also for perennial nonallergic rhinitis.1

Allergic Rhinitis

Fluticasone propionate nasal spray is used for the symptomatic treatment of seasonal or perennial allergic rhinitis.1,2,7,16,19,27,33,34,46,51,54,55,71,73,74,76,78,110,113,122,123

In patients with seasonal or perennial allergic rhinitis, intranasal administration of fluticasone propionate generally provides symptomatic relief of watery rhinorrhea, nasal congestion, sneezing, postnasal drip, and nasal itching.1,2,7,16,19,27,33,34,46,51,55,59,122,123,124 Although intranasal fluticasone propionate generally does not relieve manifestations of conjunctivitis, improvement in ophthalmic manifestations has occurred in some patients receiving the drug intranasally.19,62,110,113 Since fluticasone propionate is thought to exert a local effect on the nasal mucosa,1,2,13,22,56,67 the mechanism for these ophthalmic effects is not fully understood.19,70,94 Improvement in ophthalmic manifestations may be caused partly by a decrease in the nasolacrimal reflex, which occurs as symptoms of rhinitis improve.2,19,70,94 It also has been suggested that decreased edema of the nasal mucosa may promote better drainage of tears through the lacrimal ducts.19,118

Evidence from a limited number of studies in children 4-11 years of age suggests that intranasal fluticasone propionate 100-200 mcg daily is more effective than placebo in relieving symptoms of seasonal allergic rhinitis and is not associated with unusual adverse effects compared with those observed in adults receiving the drug;1,7,52,53,59,124 however, in one study in children, improvement in nasal symptoms with intranasal fluticasone propionate therapy was less pronounced than that generally reported in adults.52

Intranasal fluticasone propionate (200 mcg daily given in 1 or 2 divided doses in adults and adolescents) appears to be at least as effective as intranasal beclomethasone dipropionate (168 mcg twice daily) in the treatment of seasonal or perennial allergic rhinitis;16,17,22,54,69 preliminary data also suggest efficacy comparable to that of usual dosages of intranasal flunisolide acetonide.2,93 In children 6-11 years of age with perennial allergic rhinitis, intranasal fluticasone propionate (100 mcg once or twice daily) was as effective as intranasal beclomethasone dipropionate (168 mcg twice daily).124 In a limited number of studies, fluticasone propionate generally was more effective in relieving nasal symptoms in adults and adolescents than the oral antihistamines terfenadine (no longer commercially available in the US),27,33,63 astemizole (no longer commercially available in the US),2,34,58 cetirizine,2,95,112 or loratadine69,92,122 or the mast-cell inhibitor cromolyn sodium.2,21 However, in a randomized, controlled study in patients with seasonal allergic rhinitis, addition of oral cetirizine (10 mg once daily) to the usual dosage of fluticasone propionate (200 mcg once daily) did not improve control of nasal and ocular symptoms compared with fluticasone propionate therapy alone.112 Whether the very low oral bioavailability of intranasal fluticasone propionate (see Pharmacokinetics) will be associated with a reduced risk of systemic adverse effects compared with other currently available intranasal corticosteroids remains to be established.2,8,11,12,110,113,114 Current evidence suggests that 200 mcg of fluticasone propionate given once daily is as effective as 100 mcg of the drug given twice daily.2,17,46,51,54,55

In several dose-response studies in pediatric patients, once-daily administration of 100 mcg of fluticasone propionate appeared to be as effective as 200 mcg once daily; however, pediatric patients with more severe symptoms of allergic rhinitis benefited from the higher recommended dosage (200 mcg daily).1,53,59,124

In 2 double-blind, placebo (vehicle)-controlled, short-term (28-day) trials in patients 12 years of age and older with seasonal allergic rhinitis, patients using fluticasone (up to 200 mcg [2 sprays in each nostril] once daily) on an as-needed basis experienced a greater reduction in symptoms (nasal congestion, rhinorrhea, sneezing, and nasal pruritus) than patients receiving placebo.1 Study medication was used an average of 57-70% of study days for all treatment groups; the relative difference in efficacy with as-needed use compared with regularly scheduled use of fluticasone was not studied.1 Efficacy of as-needed fluticasone has not been studied in patients younger than 12 years of age with seasonal allergic rhinitis or in patients with perennial allergic or nonallergic rhinitis.1

In patients with seasonal or perennial allergic rhinitis, symptomatic relief usually is evident within 12-48 hours of continuous intranasal fluticasone propionate therapy; however, up to 2-4 days may be required for optimum effectiveness in some patients.1,13,16,27,46,48,51,52 Supplemental therapy with oral antihistamines and/or topical nasal decongestants may be necessary until an acceptable clinical response is achieved.2,52,67,75,76,77,79,80,81,96,115,120 In some patients, ophthalmic preparations may be necessary to relieve manifestations of conjunctivitis not controlled by intranasal corticosteroids.2,19,72,73,74,78,96,120 Although ophthalmic preparations containing vasoconstrictors and antihistamines or corticosteroids may be effective in relieving ophthalmic inflammatory symptoms in patients with rhinitis, concurrent use of ophthalmic and intranasal corticosteroids generally is not recommended since the risk of adverse ophthalmic effects associated with corticosteroid therapy (e.g., glaucoma, cataract formation, exacerbation of ophthalmic infections) may be increased.76,82,83,84,120 In some patients with seasonal or perennial rhinitis, especially those with concurrent asthmatic conditions, continuous concomitant therapies (e.g., oral or orally inhaled corticosteroids, bronchodilators, antihistamines, decongestants) may be required for optimum symptomatic relief;85,96,97,114,120 concomitant therapy with intranasal and other systemic corticosteroids may increase the risk of hypercorticism and/or HPA-axis suppression.79,84,110,113 (See Cautions: Precautions and Contraindications.)

Nonallergic Rhinitis

Fluticasone propionate nasal spray is used for the symptomatic treatment of perennial nonallergic rhinitis.1,2,57,113 Evidence from the majority of placebo (vehicle)-controlled studies in patients with nonallergic rhinitis indicates that intranasal administration of fluticasone propionate is associated with lower total nasal symptom scores (nasal obstruction, postnasal drip, rhinorrhea) than administration of vehicle.1,57

Fluticasone propionate has been used successfully prior to the onset of the pollen season for the prophylaxis of symptoms of seasonal allergic rhinitis†.21 In a comparative study, fluticasone propionate (200 mcg once daily) appeared to be more effective than cromolyn sodium (5.2 mg 4 times daily) in preventing nasal symptoms (e.g., sneezing, rhinorrhea, nasal congestion or itching) when the drugs were initiated at least 1 week prior to the anticipated start of the grass pollen season in patients with seasonal allergic rhinitis; both treatments were well tolerated.21 Fluticasone propionate has been used successfully by oral inhalation in the management of asthma in patients whose symptoms were not controlled by occasional use of bronchodilators.24,25,26,36,37,41

Administration

Fluticasone propionate is administered by nasal inhalation using a metered-dose nasal spray pump.1,6 Patients should be instructed carefully in the use of the nasal spray pump, including the need to prime the pump prior to first use or after a period of nonuse (i.e., 1 week or more).1,6 To obtain optimum results, patients also should be given a copy of the patient instructions provided by the manufacturer.1,6

Prior to administration of fluticasone propionate nasal spray, patients should clear their nasal passages;6 administration of a topical nasal decongestant about 5-15 minutes before intranasal corticosteroid administration may be useful during the first 2 or 3 days of therapy in patients with blocked nasal passages to ensure adequate penetration of the drug.2,67,75,79,113 Prior to initial use, the nasal inhaler must be primed.6 Patients should tilt the head slightly forward, insert the nasal adapter into one nostril,6 and point the tip of the adapter toward the inflamed nasal turbinates and away from the nasal septum.67,79 For maximum therapeutic effect and to ensure adequate penetration of the drug, patients should pump the drug into one nostril6 while holding the other nostril closed and should concurrently inspire through the nose.6 This procedure is then repeated for the other nostril.6 If sneezing occurs during drug administration, patients should wait until sneezing has stopped, then clear the nasal passages and repeat administration of the dose.120

The manufacturer recommends cleaning of the nasal spray adapter and/or pump at least once weekly.6,110 After removing the nasal adapter and dust cap, these pieces should be rinsed in warm water and dried thoroughly.6 If the nasal adapter becomes clogged, the piece should be soaked in warm water; cleaning by inserting a sharp object into the piece is not recommended.6

Dosage

The nasal inhaler delivers about 50 mcg of fluticasone propionate per metered spray.1 The commercially available preparation delivers about 120 metered sprays per 16-g bottle; the container should be discarded after the labeled number of actuations have been used since the correct dose per inhalation cannot be assured if used for additional doses.1 Dosage of intranasal fluticasone propionate should be adjusted according to individual requirements and response;1,110 the lowest effective dosage should be used in order to minimize potential systemic effects of the drug.1 (See Cautions: Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression.) The maximum daily dosage of intranasal fluticasone propionate should not exceed 100 mcg in each nostril (total of 200 mcg daily).1

Rhinitis

For the symptomatic treatment of seasonal or perennial allergic rhinitis or perennial nonallergic rhinitis, the usual initial adult dosage of fluticasone propionate nasal spray is 100 mcg (2 sprays) in each nostril once daily (200 mcg total daily dosage).1 This dosage of fluticasone propionate also may be administered as 50 mcg (1 spray) in each nostril twice daily (e.g., at 8 am and 8 pm).1,16,17,18,19,27,46,51,55

Some patients 12 years of age and older with seasonal allergic rhinitis may find as-needed use of fluticasone propionate to be effective in controlling symptoms at a dosage of 100 mcg (2 sprays) in each nostril once daily (200 mcg total daily dosage).1 However, the manufacturer states that optimal symptom control may be achieved with regularly scheduled use of fluticasone.1 If the once-daily regimen is used, some clinicians recommend administration of fluticasone propionate in the morning.18,46,110,113

In adolescents and children 4 years of age or older, the usual initial dosage of fluticasone propionate is 50 mcg (1 spray) in each nostril daily (100 mcg total daily dosage).1 Patients not responding adequately to the 100-mcg daily dosage or those with more severe symptoms may use 100 mcg (2 sprays) in each nostril daily (200 mcg total daily dosage).1

In patients with seasonal or perennial allergic rhinitis or nonallergic rhinitis, the onset of symptomatic relief may occur within 12-48 hours of initiation of intranasal fluticasone propionate therapy in adults and within 36 hours in children; however, up to 2-4 days generally is required for optimum effectiveness in most patients.1,13,16,27,46,48,51,52 There is no evidence that higher than recommended dosages or increased frequency of administration of intranasal fluticasone propionate is beneficial;13,15,110,113 exceeding the maximum recommended daily dosage may increase the risk of adverse systemic effects (e.g., HPA-axis suppression, Cushing's syndrome).1 (See Cautions: Precautions and Contraindications.) Patients should be instructed to contact their clinician during intranasal fluticasone propionate therapy if manifestations of the condition do not improve or if the condition worsens.1

Once the manifestations of seasonal or perennial allergic rhinitis or nonallergic rhinitis have been controlled, dosage of fluticasone propionate should be reduced gradually to the lowest effective level.1,96 Adults who have responded to an initial fluticasone propionate dosage of 200 mcg (2 sprays in each nostril) daily after a few days may be able to reduce their dosage to 100 mcg (1 spray in each nostril) daily for maintenance therapy.1 In pediatric patients with more severe symptoms of perennial or seasonal allergic rhinitis requiring the maximum dosage for control of symptoms (200 mcg daily), dosage should be reduced to 100 mcg (1 spray in each nostril) daily once adequate control of symptoms is achieved.1

Intranasal fluticasone propionate generally is well tolerated.1,16,18,27,34 Adverse effects with intranasal fluticasone propionate therapy usually are mild and local and resolve without specific treatment.1,16,17,46,51,55 The manufacturer states that systemic corticosteroid effects were not reported with fluticasone nasal spray in controlled trials of up to 6 months' duration, but systemic effects (e.g., growth suppression) have been reported with intranasal corticosteroids, including fluticasone propionate, during postmarketing experience.1 (See Cautions: Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression.) In clinical studies with fluticasone propionate, adverse effects required discontinuance of the drug in less than 2% of patients; this discontinuance rate was similar in patients receiving active drug or placebo (e.g., vehicle).1,19,21,27 Because some adverse effects of intranasal fluticasone propionate therapy may mimic symptoms of rhinitis (e.g., nasal congestion, nasal discharge, sinusitis, rhinorrhea), it may be difficult to distinguish drug-induced adverse effects from the underlying disease process.13,15,16,17,18,27,46,110 In some placebo-controlled and/or comparative studies, the incidence of adverse effects in patients receiving intranasal fluticasone propionate therapy was similar to that in patients receiving placebo or other active drug (e.g., oral terfenadine [no longer commercially available in the US], intranasal beclomethasone dipropionate).1,13,15,16,22,27,46,51,52,55 In adults and children with seasonal allergic rhinitis who received 50-1600 mcg of intranasal fluticasone propionate daily in 1 or 2 divided doses for 14-28 days, the incidence of adverse effects did not appear to be dose related.13,15,46,59

Nasopharyngeal or Respiratory Effects

The most frequent adverse effects of fluticasone propionate nasal spray involve the nasal mucous membranes.2,13,15,16,21,46,51 Epistaxis13,16,17,19,21,22,46,51,54,55,112,124 or sensations of nasal burning/irritation1,3,16,17,21,27,46,51,54,55 have been reported in 6-6.9 or 2.4-3.2%, respectively, of patients receiving fluticasone propionate (100-200 mcg once daily) in controlled studies.1,16,19,46 These adverse effects usually are of short duration and rarely require changes in or discontinuance of therapy.16,17,21,46,51,55,110 Sensations of nasal burning may result from excipients in the commercially available preparation since the frequency and severity of these effects are similar in patients receiving an intranasal placebo vehicle with identical inactive ingredients.1,16,17,51,110 In addition, the similar occurrence of adverse nasal effects in fluticasone propionate- or placebo-treated patients with seasonal or perennial rhinitis may result from physical contact and irritation of the characteristically sensitive nasal passages of these patients.77,79,96,110,113 Pharyngitis1,16,17,27,112 or cough1,124 has been reported in 6-7.8 or 3.6-3.8%, respectively, of patients receiving the drug.1 Symptoms of asthma1,124 have occurred in 7.2 or 3.3% of those receiving 100 or 200 mcg, respectively, of fluticasone propionate once daily.1

Other adverse nasopharyngeal or respiratory effects occurring in 1-3% of patients receiving fluticasone propionate nasal spray include nasal secretions containing blood,1,16,17,27,46,51 nasal discharge,1,21 and bronchitis.1 Sneezing,19,20 rhinorrhea,16,17,27,46,51 sinusitis,51 sore throat,1 throat irritation and dryness,1 hoarseness,1 voice changes,1 alteration or loss of sense of taste and/or smell,1 nasal congestion or blockage,1,21 or nasal dryness1,13,17,46,51 has been reported in patients receiving fluticasone propionate nasal spray in controlled studies or during postmarketing surveillance.1 Nasal septum excoriation,1,51 ulceration,1,57 or nasal septum crusting22 also has been reported in patients receiving fluticasone propionate nasal spray. It has been suggested that nasal septum crusting, nasal dryness accompanied by nasal manipulation (“picking”),105 or nasal bleeding may predispose to the development of nasal perforation,67,105 which has been reported rarely with intranasal administration of corticosteroids, including fluticasone propionate.1,67,86,110 In 2 patients who experienced nasal perforation with fluticasone propionate, both had previous septal surgery that may have increased the risk of nasal perforation.110

Localized candidal infections of the nose and/or pharynx have occurred rarely during fluticasone propionate therapy.1,17 If a candidal infection is suspected, appropriate local anti-infective therapy and/or discontinuance of intranasal corticosteroid therapy should be considered.1,115 Upper respiratory infection also has been reported with intranasal fluticasone propionate therapy, but a causal relationship to the drug has not been established.18,22,110,112

Although not reported to date in patients receiving fluticasone propionate or other intranasal corticosteroids, some clinicians caution that atrophic rhinitis potentially could develop during chronic therapy with an intranasal corticosteroid, since atrophic dermatitis has occurred in patients treated with topical corticosteroids to the skin for prolonged periods.67,75,82,105,120 However, the theoretical potential for nasal atrophy is thought to be less than that for atrophic dermatitis because of the smaller residence time of the intranasal corticosteroid on the nasal mucosa compared with that of topical corticosteroids on the skin.105,110 Rhinoscopic assessment or nasal examination of patients with rhinitis treated continuously with intranasal fluticasone propionate for 6-12 months has shown no evidence of serious mucosal damage.2,17,22

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression

Adrenal suppression, based on mean plasma cortisol, morning plasma cortisol, or urinary 17-ketogenic steroid (17-KS) determinations, has not been observed to date when fluticasone propionate was administered intranasally in adults receiving 200 mcg daily for up to 12 months or in children (aged 4-11 years) receiving intranasal fluticasone spray 100-200 mcg daily for 2-4 weeks.1,2,17,22,51,52,53,110,123 In addition, no evidence of growth suppression was noted in a 1-year, placebo-controlled study in children 3-9 years of age receiving fluticasone propionate 200 mcg once daily.1 (See Cautions: Pediatric Precautions.)However, growth suppression has been reported during other controlled clinical trials in children receiving intranasal corticosteroids,1,126,127 in the absence of laboratory evidence of HPA-axis suppression.1 This finding suggests that growth velocity may be a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA-axis function.1 While no clinically important alterations in plasma cortisol were observed in patients with asthma receiving orally inhaled fluticasone propionate dosages of 200-1500 mcg daily for up to 1 year,24,25,26,36,37,39,110 a relationship between plasma fluticasone propionate concentrations and inhibitory effects on stimulated cortisol production has been demonstrated after 4 weeks of treatment with fluticasone propionate inhalation aerosol.125 When administered orally (formulation currently not commercially available in the US) in single doses of up to 16 mg in healthy adults, fluticasone propionate did not appreciably affect plasma cortisol concentrations.8,111 However, evidence of HPA-axis suppression has been observed with oral fluticasone propionate therapy (20 mg daily) in several patients with distal ulcerative colitis or celiac disease; some of these patients had abnormal baseline ACTH-stimulated cortisol responses.30,47 In healthy males receiving oral fluticasone propionate (formulation currently not commercially available in the US) 10-20 mg 4 times daily for 10 days, mean plasma and urinary cortisol concentrations were reduced; approximately 11% of the individuals discontinued the drug because of HPA-axis suppression.111 The manufacturer states that although systemic effects have been minimal with recommended doses of fluticasone propionate nasal spray, the potential risk of such effects increases with larger doses; therefore, larger-than-recommended doses of fluticasone propionate nasal spray should be avoided.1 The effect of intranasal fluticasone propionate on the HPA-axis response to stress (e.g., surgery) is not known.110,113 Intranasal administration of usual dosages of fluticasone propionate apparently produces less HPA-axis suppression than intranasal administration of usual dosages of dexamethasone phosphate; however, comparative studies have not been conducted to date.8

Other Adverse Effects

Headache1,112,124 has been reported in 6.6-16.1% of patients receiving intranasal fluticasone propionate therapy (100-200 mcg once daily).1 Menstrual cramps18,110 also have been reported in patients receiving the drug, although a causal relationship has not been established. Nausea and vomiting1,21 have been reported in 2.6-4.8% of adults and children receiving fluticasone (100-200 mcg once daily) in controlled clinical trials.1 Dizziness,1 abdominal pain,1 diarrhea,1 fever,1 flu-like symptoms,1,124 or aches and pains1 have been reported in 1-3% of adults and children receiving fluticasone in controlled clinical trials.1 Drowsiness/lethargy/fatigue or arthralgia has occurred infrequently in patients receiving intranasal fluticasone propionate.112 Immediate hypersensitivity reactions (e.g., wheezing, contact dermatitis, rash, dyspnea, anaphylaxis/anaphylactoid reactions, pruritus, urticaria, angioedema, edema of the face and tongue, bronchospasm) have been reported during postmarketing surveillance or in controlled clinical trials with intranasal administration of fluticasone propionate.1,112

Cataracts, ocular dryness and irritation, conjunctivitis, blurred vision, glaucoma, and increased intraocular pressure have been reported with intranasal administration of corticosteroids, including fluticasone.1,17,84 In a controlled, comparative study, ophthalmologic abnormalities (e.g., retinal changes, lenticular opacities) were noted after 12 and 24 weeks of therapy in a similar percentage of patients receiving intranasal fluticasone propionate, beclomethasone, or placebo; however, none of the ocular changes were of the type attributed to systemic effects of corticosteroid therapy (e.g., posterior subcapsular cataracts, increased intraocular pressure).17

Precautions and Contraindications

Although systemic effects have been minimal with recommended dosages of fluticasone propionate nasal spray, potential risk increases with higher dosages.1 Therefore, higher than recommended dosages of fluticasone propionate nasal spray should be avoided since hypercorticism and suppression of HPA function may occur.1 If such systemic effects occur, the dosage of fluticasone propionate nasal spray should be reduced slowly and the drug discontinued in accordance with accepted procedures for discontinuing oral corticosteroid therapy.1 (See Discontinuance of Therapy under Dosage and Administration: Dosage, in the Corticosteroids General Statement 68:04.)

Fluticasone propionate nasal spray should be used with caution in patients receiving systemic corticosteroids in an alternate-day or daily dosing regimen for any disease,1 since concomitant use of the drugs could increase the likelihood of HPA-axis suppression compared with therapeutic dosages of either drug alone.1,115 In addition, concomitant use of fluticasone propionate nasal spray with other inhaled corticosteroids could increase the risk of manifestations of hypercorticism and/or suppression of HPA function.1

Patients who have received systemic corticosteroids for prolonged periods and are being switched to treatment with topical corticosteroids (e.g., fluticasone propionate nasal spray) should be monitored carefully since corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression), acute adrenal insufficiency, or severe symptomatic exacerbation of asthma or other clinical conditions may occur.1,115 (See Discontinuance of Therapy under Dosage and Administration: Dosage, in the Corticosteroids General Statement 68:04.)

Although manifestations of Cushing's syndrome (e.g., hypertension, glucose intolerance, cushingoid features) have not been associated with intranasal fluticasone propionate therapy to date, the possibility of their occurrence should be considered in patients who are particularly sensitive to corticosteroid effects or when usual dosages of the drug are exceeded.1,110,113

Patients should be advised that intranasal fluticasone propionate should be used at regular intervals to be therapeutically effective.1,110 In addition, patients generally should be advised that the full benefits of the drug may not be achieved for several days1,6,13,16,27,46,48,51,52,115 and that use of topical nasal decongestants or oral antihistamines may be necessary until the effects of intranasal fluticasone propionate therapy are fully manifested.2,52,67,75,76,77,79,80,81,113 Patients also should be advised not to exceed the prescribed dosage.1 (See Dosage and Administration: Dosage.) Patients with severe allergies should be instructed to avoid exposure to allergens during intranasal fluticasone propionate therapy to prevent the occurrence of severe allergic symptoms in the eyes and/or lower respiratory tract.18,46,51,71,73,74,75,76,78,80 Patients should be instructed to contact their physician during intranasal fluticasone propionate therapy if signs or symptoms of the condition do not improve, if the condition worsens, or if sneezing or nasal irritation occurs.1

Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.1,32,86,87 Because of the inhibitory effect of these drugs on wound healing,1,32,86,87 patients with recent nasal septal ulcers, nasal surgery, or nasal trauma should not use intranasal corticosteroids until healing has occurred.1,110,113,115 Intranasal fluticasone propionate therapy should be used with extreme caution, if at all, in patients with clinical tuberculosis or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract; untreated fungal or bacterial infections; or ocular herpes simplex or untreated, systemic viral infections.1 During long-term therapy with fluticasone propionate (several months or longer),1 the nasal passages should be examined periodically for mucosal changes and for signs of candidiasis.1,104,105,119 If such infections occur, appropriate local treatment of the infection may be necessary115 and/or discontinuance of intranasal fluticasone propionate therapy may be required.1,17

Patients who are taking immunosuppressant drugs while receiving corticosteroids have increased susceptibility to infections compared with healthy individuals, and certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients, particularly in children.1,32,86,87 In patients who have not had these diseases, particular care should be taken to avoid exposure.1 The relationship of dose, route of administration, and duration of corticosteroid therapy to the risk of developing a disseminated infection is not known, nor is the contribution of the underlying disease and/or prior corticosteroid therapy.1,86,89 Patients receiving corticosteroids who are potentially immunosuppressed should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs.1,89,98,99,100 If exposure to varicella or measles occurs in such individuals, administration of varicella zoster immune globulin (VZIG) or immune globulin, respectively, may be indicated.1,89 If varicella develops, treatment with an antiviral agent (e.g., acyclovir) may be considered.1,86,88,89 For additional information, see Cautions: Increased Susceptibility to Infection and also see Precautions and Contraindications, in the Corticosteroids General Statement 68:04.

Fluticasone propionate nasal spray is contraindicated in patients with known hypersensitivity to the drug or other ingredients in the formulation (the formulation does not contain fluorocarbons).1,110

Pediatric Precautions

The manufacturer states that safety and efficacy of fluticasone propionate nasal spray in children younger than 4 years of age have not been established.1

Use of excessive dosages of corticosteroids may lead to manifestations of hypercorticism, suppression of HPA function, and/or suppression of growth in children or adolescents.1,32,38,82,87 Inhibitory effects on short-term growth rate (as determined by knemometry studies of lower leg growth) have been observed in asthmatic children and adolescents receiving orally inhaled corticosteroids (e.g., beclomethasone dipropionate, fluticasone propionate).38 However, the relationship between short-term changes in lower leg growth and long-term effects on growth currently are unclear.38,106,107 In a placebo-controlled, 1-year study in children 3-9 years of age, normal growth velocity was not adversely affected by intranasal fluticasone propionate 200 mcg once daily.1 No evidence of clinically relevant changes in HPA axis function (as assessed by 12-hour urinary cortisol excretion) or bone mineral density (as assessed by dual x-ray absorptiometry) was observed in such children.1 However, therapy with intranasal corticosteroids has caused a reduction in growth velocity in pediatric patients in other controlled clinical trials,1,126 even in the absence of laboratory evidence of suppression of HPA function.1 The potential for fluticasone propionate nasal spray to cause growth suppression in susceptible patients or at dosages exceeding 200 mcg daily cannot be ruled out.1 The long-term effects of reduction in growth velocity with intranasal corticosteroids, including the impact on final adult height, are unknown.1,126 The potential for catch-up growth following discontinuance of treatment with intranasal corticosteroids has not been adequately studied.1 Clinicians should monitor closely (e.g., via stadiometry) the growth of children and adolescents taking corticosteroids by any route of administration;1 if growth rate is affected, the clinician should weigh the potential benefits of corticosteroid therapy against the possibility of growth suppression.1

Geriatric Precautions

Fluticasone propionate nasal spray has not been evaluated extensively in geriatric patients to date.1 However, data from US and non-US clinical trials in geriatric patients receiving intranasal fluticasone propionate have not revealed evidence of unusual age-related differences in adverse effects.1

Mutagenicity and Carcinogenicity

No evidence of mutagenicity was observed in vitro in prokaryotic or eukaryotic cells when fluticasone propionate was tested in in vitro studies including the Ames microbial ( Salmonella typhimurium ) mutagen test, Escherichia coli fluctuation test, and Saccharomyces cerevisiae gene conversion test.65,66,110 When tested in in vitro mammalian cell cytogenetic studies, including Chinese hamster ovary and cultured human peripheral lymphocytes, fluticasone propionate did not appear to cause chromosomal damage.1,65,66,110 No evidence of adverse chromosomal effects was observed in an in vivo micronucleus test in mice receiving high doses of fluticasone propionate by the oral or subcutaneous routes.1 Furthermore, the drug did not delay erythroblast division in bone marrow.1

No evidence of carcinogenicity was seen in mice receiving oral fluticasone propionate dosages up to 1 mg/kg (approximately 20 times the maximum recommended daily intranasal dosage in adults and approximately 10 times the maximum recommended daily intranasal dosage in children on a mcg/m² basis) for 78 weeks or in rats receiving inhaled fluticasone propionate dosages up to 57 mcg/kg (approximately 2 times the maximum recommended daily intranasal dosage in adults and approximately equivalent to the maximum recommended daily intranasal dosage in children on a mcg/m² basis) for 104 weeks.1

Pregnancy, Fertility, and Lactation

Pregnancy

Fluticasone propionate nasal spray should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.1 Since adrenal insufficiency may occur in neonates born to women who received corticosteroids during pregnancy, these neonates should be monitored carefully for manifestations of this condition.110 Although there are no adequate and well-controlled studies to date using fluticasone propionate in pregnant women, fluticasone propionate has been shown to be teratogenic and embryotoxic in mice or rats when administered subcutaneously at daily dosages of 45 or 100 mcg/kg, respectively (approximately equivalent to 4 times the maximum recommended daily intranasal dosage in adults based on surface area).1,110 Observed fetal toxicity was characteristic of potent glucocorticoid compounds and included embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification.1,48 Fetal weight reduction and cleft palate were observed in offspring of rabbits given fluticasone propionate 4 mcg/kg subcutaneously (less than the maximum recommended daily intranasal dosage in adults).1 Following oral administration of up to 300 mcg/kg (approximately 25 times the maximum recommended daily intranasal dosage in adults on a mcg/m² basis) daily of fluticasone propionate in rabbits, the drug was not detected in plasma, and no maternal effects nor increased incidence of external, visceral, or skeletal fetal defects was detected.1,110 The low bioavailability and small distribution of fluticasone propionate across the placenta may account for the lack of teratogenicity; in rats and rabbits receiving oral fluticasone propionate dosages of 100 mcg/kg (590 mcg/m²) or 300 mcg/kg (3.6 mg/m²), respectively, less than 0.008% of the dose crossed the placenta.1,48 Long-term experience with the use of oral glucocorticoids suggests that rodents are more prone to teratogenic effects of glucocorticoids than humans.1 In addition, because there is a natural increase in glucocorticoid production during pregnancy, most women will require a lower exogenous glucocorticoid dose and many will not need glucocorticoid treatment during pregnancy.1,48

Fertility

Reproduction studies in rats using subcutaneous fluticasone propionate at daily dosages of 50 mcg/kg (approximately 2 times the maximum recommended daily intranasal dosage in adults on a mcg/m² basis) have shown no evidence of impaired fertility.1 However, prostate weight was substantially reduced in rats at a subcutaneous dose of 50 mcg/kg.1,110

Lactation

Fluticasone propionate should be used with caution in nursing women, since it is not known whether the drug is distributed into milk in humans.1 Subcutaneous administration of tritiated fluticasone propionate to lactating rats (10 mcg/kg, less than the maximum recommended daily intranasal dosage in adults on a mcg/m² basis) resulted in measurable radioactivity in both plasma and milk.1,48 Other corticosteroids are distributed into milk and in systemic amounts may cause adverse effects, such as growth suppression, in nursing infants.1,86,87,90,91,110,115

Drugs Affecting Hepatic Microsomal Enzymes

Since fluticasone propionate is metabolized in the liver by the cytochrome P-450 (CYP) 3A4 isoenzyme, concomitant use of drugs that affect CYP hepatic microsomal enzymes could alter the metabolism of fluticasone.1 In a multiple-dose, crossover study, concomitant use of intranasal fluticasone propionate (200 mcg once daily) and ritonavir (100 mg twice daily), a highly potent CYP3A4 inhibitor, increased peak plasma concentrations and area under the plasma concentration-time curve (AUC) of fluticasone, resulting in an 86% decrease in the plasma cortisol AUC.1 Cushing syndrome and adrenal suppression have been reported during postmarketing experience in patients receiving concomitant therapy with fluticasone propionate and ritonavir.1 Concomitant use of fluticasone propionate and ritonavir is not recommended unless the potential benefit is considered to outweigh the risk of systemic corticosteroid adverse effects.1

Concomitant use of ketoconazole reportedly may inhibit the metabolism of fluticasone through the inhibition of the CYP3A4 system.1 Administration of a single dose of orally inhaled fluticasone propionate (1 mg or 5 times the maximum daily intranasal dose) in healthy individuals receiving ketoconazole (200 mg once daily until steady-state reached) increased mean plasma fluticasone concentrations, resulting in a depression of certain indices of HPA-axis function (as determined by a reduction in plasma cortisol area under the plasma concentration-time curve).1 Concomitant administration of multiple doses of erythromycin (333 mg 3 times daily) with orally inhaled fluticasone propionate (500 mcg twice daily) did not affect the pharmacokinetics of fluticasone.1 Care should be exercised when fluticasone is administered concomitantly with other potent CYP3A4 inhibitors.1

Corticosteroids

Concomitant use of fluticasone propionate nasal spray with other inhaled and/or systemically absorbed corticosteroids could increase the risk of hypercorticism and/or suppression of the HPA axis.1,79,84 (See Cautions: Precautions and Contraindications.)

Acute Toxicity

Limited information is available on the acute toxicity of fluticasone propionate.1,28,48 No evidence of toxicity was noted in healthy adults receiving intranasal fluticasone propionate 2 mg twice daily for 7 days (10 times the recommended dosage).1,48 In addition, oral administration of up to 16 mg of fluticasone propionate in single doses has not been reported to cause toxicity in healthy individuals.1,8 However, HPA-axis suppression reportedly has occurred in healthy individuals receiving fluticasone propionate orally in dosages of 40-80 mg daily (10-20 mg 4 times daily) for 10 days.111

In animals receiving high-dose fluticasone propionate subcutaneously, orally, and by inhalation, reversible thymus gland depletion and gastric ulcer were noted.111 The LD₅₀ of fluticasone propionate has not been determined but is greater than 1000 mg/kg in rats after oral or subcutaneous administration, greater than 2 mg/kg after IV administration in rats, greater than 1.66 mg/kg after inhalation in rats, and greater than 0.82 mg/kg after inhalation in dogs; these dosages represent approximately 300,000, 700, 550, and 275 times, respectively, the usual intranasal dosage of fluticasone propionate in humans on a mcg/kg basis, not accounting for systemic bioavailability.111 The usual dosage of intranasal fluticasone propionate in a 70-kg adult is 3 mcg/kg daily; the actual systemic exposure is far less because systemic bioavailability following intranasal administration is less than 2%.111

Pharmacology

Fluticasone propionate is a highly selective agonist at the human glucocorticoid receptor with negligible activity at androgen, estrogen, or mineralocorticoid receptors.48,110,113,117 In preclinical studies, fluticasone propionate reportedly exhibited weak progesterone-like activity.1,103,110 However, as plasma concentrations of fluticasone propionate are very low following intranasal administration of the drug in recommended doses, the clinical importance of this finding is not known.1 The therapeutic effects of fluticasone propionate are thought to result from local actions of the deposited inhaled dose on the nasal mucosa rather than from the systemic actions of the swallowed portion of the dose.1,13,22,56,67

Following topical application to the nasal mucosa, fluticasone propionate produces anti-inflammatory and vasoconstrictor effects.17,22,55,58,63 In vitro receptor binding studies demonstrate that fluticasone propionate is 3-14 times as potent as dexamethasone in binding to the glucocorticoid receptor and in initiating gene expression.1,110,117 The half-life for the fluticasone propionate-glucocorticoid receptor complex was 10 hours.117 The anti-inflammatory potency of topically applied fluticasone propionate, as measured by a vasoconstrictor assay, is about 13 times greater than that of triamcinolone acetonide, 9 times greater than that of fluocinolone acetonide, 3 times greater than that of betamethasone valerate, and 2 times greater than that of beclomethasone dipropionate.2,3,103 The exact mechanism(s) of anti-inflammatory action of corticosteroids in allergic rhinitis remains unknown, but may involve reductions in the following: number of mediator cells (basophils,2,5,7,13,17,27,35,46,51,55,57,58 eosinophils,2,4,5,7,9,13,17,27,35,46,50,51,55,57,58,60,61,63,116 helper-inducer [CD4⁺, T4⁺] T-cells,4,60,116 mast cells,7,50,60,61,116 and neutrophils)2,7,13,35 in the nasal mucosa, nasal reactivity to allergens, and release of inflammatory mediators63 and proteolytic enzymes.63 Following exposure of patients with a history of allergic rhinitis to allergen, eosinophils, basophils, mast cells, T cells, and neutrophils appear to infiltrate nasal secretions and mucosa, releasing inflammatory mediators that generate allergic responses such as pruritus, sneezing, rhinorrhea, and nasal edema.2,4,5,9,10,13,14,35 Fluticasone propionate therapy has reduced nasal eosinophils,1,116 basophils, and neutrophils more often than placebo in adults with seasonal or perennial allergic rhinitis;1,2,13,17,46,51 however, the relationship of these findings, if any, to long-term symptomatic relief in patients with allergic rhinitis is not known.1,110,113,116 In a comparative study in patients with allergic rhinitis receiving intranasal fluticasone propionate or oral astemizole (no longer commercially available in the US), fluticasone propionate was more effective than astemizole in decreasing symptoms of allergic rhinitis and in decreasing nasal basophils and eosinophils; astemizole did not affect nasal basophils or eosinophils.53 Data from another comparative study with beclomethasone dipropionate (168 mcg twice daily) and fluticasone propionate (200 mcg daily) showed that both agents were equivalent in reducing eosinophil and basophil levels and in decreasing nasal symptoms of allergic rhinitis.17 Intranasal fluticasone propionate also was more effective than oral terfenadine (no longer commercially available in the US) in decreasing the release of histamine and tryptase in the nasal mucosa and in decreasing nasal symptoms of allergic rhinitis; both drugs reduced eosinophils, while neither agent had an effect on basophil levels.63 Reductions in nasal histamine and tryptase content appeared to correlate with greater symptom control in patients receiving fluticasone propionate versus those receiving terfenadine.63

Other mechanisms by which corticosteroids may improve symptoms of allergic rhinitis may involve inhibition of postcapillary venule dilation and permeability and facilitation of nasomucociliary clearance of nasal secretions.22,55,62 Patients receiving short- and long-term treatment with intranasal fluticasone propionate have demonstrated decreases in nasal turbinate swelling and mucosal inflammation.22,55 As inflammatory changes occur during periods of increased nasal hyperresponsiveness, the degree of response to nasal secretory stimuli has been used as an indirect measure of inflammation.2,22,27,34,40,41,48 In patients with asymptomatic seasonal allergic rhinitis, pretreatment with intranasal fluticasone propionate for 2-6 weeks prior to challenge with allergens4,5,10,14,49 or inflammatory mediators5 generally reduced the release of tryptase,2,5,10 histamine,49 eosinophilic cationic protein,5,14 and prostaglandin D₂49 in nasal biopsies or nasal lavage fluid; concentrations of eosinophils2,4,5 or activated eosinophils,9,14 CD4⁺ T-cells,4 and basophils also were reduced.5 In several placebo-controlled studies, fluticasone propionate decreased the degree of nasal hyperreactivity (as measured by amounts of nasal secretions and sneezing) to increasing concentration of secretory stimuli (e.g., allergen, histamine).2,4,5,9,10,49 Pretreatment with fluticasone propionate at the recommended dosage (200 mcg daily) for 2 weeks did not affect the increase in nasal airway resistance noted after nasal allergen challen however, pretreatment with higher dosages (400 mcg daily) increased nasal inspiratory peak flow following allergen challenge.9,14,49

Adrenal suppression, based on mean plasma cortisol or urinary 17-ketogenic steroid (17-KS) determinations, has not been observed to date when intranasal fluticasone propionate was administered in dosages of 200-4000 mcg daily for up to 12 months.1,2,8,13,15,16,17,20,22,55,110 (See Cautions: Hypothalamic-Pituitary-Adrenal [HPA] Axis Suppression.)

Pharmacokinetics

Limited data are available on the pharmacokinetics of fluticasone propionate following intranasal administration.2,7,8 Because of the drug's low systemic bioavailability when administered intranasally, most pharmacokinetic data for fluticasone propionate are based on studies in which the drug was administered IV or orally.2,7,8

Absorption

Fluticasone propionate is poorly absorbed from the respiratory and GI tracts following nasal inhalation of the drug as an aqueous spray.8,51,52 Based on indirect calculations, intranasal fluticasone propionate has an absolute systemic bioavailability of less than 2%.1,7 A major portion of an intranasal dose of corticosteroids is swallowed and undergoes extensive first-pass metabolism in the liver.2,8,51,52,67,103 (See Pharmacokinetics: Elimination.)In patients with allergic rhinitis receiving intranasal fluticasone propionate for 2-3 weeks, plasma concentrations were above the level of detection of the assay (50 pg/mL) only when recommended dosages were exceeded, and in those instances, only in occasional samples at low concentrations.1,48,56 Current evidence suggests that the therapeutic effects of intranasal fluticasone propionate can be attributed to the topical effects of the drug on the nasal mucosa.1,13,22,56

Limited data from studies in which radiolabeled fluticasone propionate has been administered orally indicate that the drug is poorly absorbed from the GI tract and undergoes rapid first-pass metabolism in the liver.2,8,11 Preliminary data from a dose-ranging study suggests that the amount of unchanged fluticasone propionate in plasma increases with dose following oral administration, but the bioavailability of the radiolabeled drug averaged about 1%2 or less after oral doses of 1-40 mg.8,11 Additional studies are needed to determine the oral bioavailability of fluticasone propionate.12

Following oral administration of 1 or 16 mg of radiolabeled propionylfluticasone in a few healthy individuals, peak plasma radioactivity levels (expressed as fluticasone propionate equivalents) averaging approximately 1.3 or 9.1 ng/mL, respectively, were achieved within 0.5-6 hours.2,8,110 Since no unchanged fluticasone propionate was detected in plasma for up to 6 hours after oral administration of unlabeled fluticasone propionate given on a separate occasion,2,7,8 the plasma radioactivity noted after administration of the radiolabeled drug was presumed to be fluticasone propionate metabolites.2,8 It has been suggested that the presence of small amounts (50-170 pg/mL) of fluticasone propionate in plasma from 6-24 hours after the dose in these individuals potentially may represent rectal reabsorption of unmetabolized drug.2,7,8,10,103

In patients with seasonal or perennial allergic or nonallergic rhinitis, the onset of symptomatic relief may occur within 12-48 hours of initiation of intranasal fluticasone propionate therapy in adults and within 36 hours in children; however, up to 2-4 days generally are required for optimum effectiveness in most patients.1,13,16,27,46,48,51,52 Following discontinuance of intranasal fluticasone propionate therapy, symptoms of rhinitis generally do not recur for 1-2 weeks.10,13,16,27,46,48,52,62

Distribution

Although fluticasone propionate is widely distributed into most tissues following IV administration, distribution of the drug following intranasal administration has not been described.1 Following IV administration, the volume of distribution for fluticasone propionate is 4.2 L/kg.1 Fluticasone propionate is approximately 91% bound to human plasma proteins; protein binding demonstrates no obvious relationship to drug concentration.1,48 Fluticasone propionate is weakly and reversibly bound to erythrocytes and equilibrates freely between erythrocytes and plasma.1,8,12,48 Fluticasone propionate is not appreciably bound to human transcortin (corticosteroid-binding globulin).1,48

Fluticasone propionate crosses the placenta in rats or rabbits following oral administration of fluticasone propionate 100 or 300 mcg/kg, respectively (approximately 4 or 25 times, respectively, the maximum daily intranasal dosage in adults on a mcg/m² basis).1 It is not known if fluticasone propionate is distributed into human milk following intranasal administration;1 however, other corticosteroids are distributed into human milk.1,115 In lactating rats, subcutaneous administration of tritiated fluticasone propionate (10 mcg/kg, approximately one-third the maximum recommended daily intranasal dosage in adults on a mcg/m² basis) resulted in measurable radioactivity in both plasma and milk.1

Elimination

The apparent elimination half-life of fluticasone propionate after IV administration is approximately 3 hours.1,7,8,48,103 Plasma clearance of the drug ranges from 623-998 mL/minute; total blood clearance (plasma clearance adjusted for packed cell volume) of IV fluticasone propionate averages 1093 mL/minute1 and approximates that of liver blood flow,2,103 with renal clearance accounting for less than 0.02% of total body clearance.1,7,8,48,110

Fluticasone propionate is rapidly metabolized in the liver by the cytochrome P-450 isoenzyme CYP3A4; the principal metabolite is the inactive 17β-carboxylic acid derivative.1,3,8,48,117 Following oral administration of radiolabeled drug, less than 5% of the dose was excreted in urine.2,7,8,48,103 Of the total radioactivity recovered in urine, 18% represented the inactive 17β-carboxylic acid derivative of fluticasone propionate, 12% represented a less polar metabolite, and the remainder represented more polar metabolites.2,7,8,103 Total fecal excretion of fluticasone propionate has been reported to range from 8714 -100% of the oral dose.2,7,8,48,103 In 2 healthy men receiving oral fluticasone propionate, fecal recovery of unchanged drug was 9 and 20% after a 1-mg dose and 54 and 75% after a 16-mg dose.2,103 The increase in fecal excretion of unchanged fluticasone propionate with increased dose has been attributed to insolubility of the drug rather than to biliary elimination.8 The 17β-carboxylic acid metabolite of fluticasone propionate accounted for 3-40% of fecal excretion.2,7,8 When a single oral 5-mg dose of fluticasone propionate was administered to patients with an ileostomy, 73% of the dose was recovered in the ileostomy effluent within 12 hours.30

Chemistry and Stability

Chemistry

Fluticasone propionate is a synthetic trifluorinated corticosteroid.1,2,3,6,7,8,26,48,65,66 Unlike currently available corticosteroids, the drug is synthesized from a 19-carbon androsterone nucleus rather than a 21-carbon pregnane nucleus.3,7 Halogenation at positions 6 and 9 and addition of a double bond at the 1,2 position of the androsterone molecule increases the anti-inflammatory activity of fluticasone propionate.3 Esterification of the oxygen at position 17 of androsterone nucleus enhances the topical anti-inflammatory activity87 of fluticasone propionate as compared with compounds such as betamethasone.3,110 Addition of a fluoromethyl carbothioate group at position 17 also increases the anti-inflammatory activity of fluticasone propionate as compared with compounds such as beclomethasone dipropionate.3 This 17β substitution may facilitate enzymatic hydrolysis to inactive metabolites.3,110

Fluticasone propionate occurs as a white to off-white powder.1 The drug has solubilities of 450 mg/mL in dimethylsulfoxide or dimethylformamide, less than 10 mg/mL in methanol or 95% ethanol, and less than 1 mg/mL in water.1,103,110

For intranasal use, fluticasone propionate is commercially available as a metered-dose pump spray containing a microcrystalline suspension of the drug in an aqueous vehicle.1 After initial priming, each actuation of the spray pump delivers from the nasal adapter a dose of 50 mcg of fluticasone propionate.1

Stability

Fluticasone propionate nasal pump spray should be stored at 4-30°C.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. GlaxoSmithKline. Flonase^® (fluticasone propionate) nasal spray 50 mcg prescribing information. Research Triangle Park, NC; 2004 Mar.

2. Bryson HM, Faulds D. Intranasal fluticasone propionate: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in allergic rhinitis. Drugs . 1992; 43:760-75. [PubMed 1379151]

3. Phillipps GH. Structure-activity relationships of topically active steroids: the selection of fluticasone propionate. Respir Med . 1990; 84(Suppl A):19-23. [PubMed 2287791]

4. Masuyama K, Jacobson MR, Rak S et al. Topical glucocorticosteroid (fluticasone propionate) inhibits cells expressing cytokine mRNA for interleukin-4 in the nasal mucosa in allergen-induced rhinitis. Immunology . 1994; 82:192-9. [PubMed 7927488][PubMedCentral]

5. Konno A, Yamakoshi T, Terada N et al. Mode of action of a topical steroid on immediate phase reaction after antigen challenge and nonspecific nasal hyperreactivity in nasal allergy. Int Arch Allergy Immunol . 1994; 103:79-87. [PubMed 8260854]

6. Allen and Hanburys. Flonase^® (fluticasone propionate) nasal spray 0.05% patient information. Research Triangle Park, NC. 1994 Sep.

7. Allen and Hanburys, Research Triangle Park, NC: Personal communication.

8. Harding SM. The human pharmacology of fluticasone propionate. Respir Med . 1990; 84(Suppl A):25-9. [PubMed 2287792]

9. Thomas KE, Greenwood L, Murrant N et al. The effects of topical fluticasone propionate on allergen-induced immediate nasal airways response and eosinophil activation: preliminary results. Respir Med . 1990; 84(Suppl A):33-5. [PubMed 2287795]

10. Juliusson S, Holmberg K, K et al. Mast cells and mediators in the nasal mucosa after allergen challenge. Effects of four weeks' treatment with topical glucocorticoid. Clin Exp Allergy . 1993; 23:591-9. [PubMed 7693314]

11. Bye A. The oral systemic availability of fluticasone propionate in man—preliminary data. Br J Clin Pharmacol . 1993; 36:12-3.

12. Andersson P, Brattsand R, Dahlstrom K et al. Oral availability of fluticasone propionate. Br J Clin Pharmacol . 1993; 36:135-6. [PubMed 8398584][PubMedCentral]

13. Meltzer EO, Orgel HA, Bronsky EA et al. A dose-ranging study of fluticasone propionate aqueous nasal spray for seasonal allergic rhinitis assessed by symptoms, rhinomanometry, and nasal cytology. J Allergy Clin Immunol . 1990; 86:221-30. [PubMed 2200821]

14. Lozewicz S, Wang J, Duddle J et al. Topical glucocorticoids inhibit activation by allergen in the upper respiratory tract. J Allergy Clin Immunol . 1992; 89:951-7. [PubMed 1583252]

15. van As A, Bronsky E, Grossman J et al. Dose tolerance study of fluticasone propionate aqueous nasal spray in patients with seasonal allergic rhinitis. Ann Allergy . 1991; 67:156-62. [PubMed 1867454]

16. Ratner PH, Paull BR, Findlay SR et al. Fluticasone propionate given once daily is as effective for seasonal allergic rhinitis as beclomethasone dipropionate given twice daily. J Allergy Clin Immunol . 1992; 90:285-91. [PubMed 1527313]

17. van As A, Bronsky EA, Dockhorn RJ et al. Once daily fluticasone propionate is as effective for perennial allergic rhinitis as twice daily beclomethasone diproprionate. J Allergy Clin Immunol . 1993; 91:1146-54. [PubMed 8509578]

18. Dolovich J, O'Connor M, Stepner N et al. Double-blind comparison of intranasal fluticasone propionate, 200mcg, once daily with 200mcg twice daily in the treatment of patients with severe seasonal allergic rhinitis to ragweed. Ann Allergy . 1994; 72:435-40. [PubMed 8179230]

19. Dolovich J, Wong AG, Chodirker WB et al. Multicenter trial of fluticasone propionate aqueous nasal spray in ragweed allergic rhinitis. Ann Allergy . 1994; 73:147-53. [PubMed 8067598]

20. Vargas R, McMahon FG, Dockhorn R et al. An assessment of HPA axis effects of fluticasone propionate aqueous nasal spray using 6-hr ACTH infusion. Clin Pharmacol Ther . 1994; 55:184.

21. Bousquet J, Chanal I, Alquié MC et al. Prevention of pollen rhinitis symptoms: comparison of fluticasone propionate aqueous nasal spray and disodium cromoglycate aqueous nasal spray: a multicenter, double-blind, double-dummy, parallel-group study. Allergy . 1993; 48:327-33. [PubMed 8368459]

22. Haye R, Gomez EG. A multicentre study to assess long-term use of fluticasone propionate aqueous nasal spray in comparison with beclomethasone dipropionate aqueous nasal spray in the treatment of perennial rhinitis. Rhinology . 1993; 31:169-74. [PubMed 8140383]

23. O'shaughnessy KM, Wellings R, Gillies B et al. Differential effects of fluticasone propionate on allergen-evoked bronchoconstriction and increased urinary leukotriene E₄ excretion. Am Rev Respir Dis . 1993; 147:1472-6. [PubMed 8389108]

24. Gustafsson P, Tsanakas J, Gold M et al. Comparison of the efficacy and safety of inhaled fluticasone propionate 200 mcg/day with inhaled beclomethasone dipropionate 400 mcg/day in mild and moderate asthma. Arch Dis Child . 1993; 69:206-11. [PubMed 8215522][PubMedCentral]

25. Leblanc P, Mink S, Keistinen T et al. A comparison of fluticasone propionate 200 mcg/day with beclomethasone dipropionate 400 mcg/day in adult asthma. Allergy . 1994; 49:380-5. [PubMed 8092438]

26. Fabbri L, Burge PS, Croonenborgh L et al. Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. Thorax . 1993; 48:817-23. [PubMed 8211872][PubMedCentral]

27. van Bavel J, Findlay SR, Hampel FC et al. Intranasal fluticasone propionate is more effective than terfenadine tablets for seasonal allergic rhinitis. Arch Intern Med . 1994; 154:2699-704. [PubMed 7993153]

28. Hawthorne AB, Record CO, Holdsworth CD et al. Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis. Gut . 1993; 34:125-8. [PubMed 8432442][PubMedCentral]

29. Zaitoun A, Record CO. Morphometric studies in duodenal biopsies from patients with coeliac disease: the effect of the steroid fluticasone propionate. Aliment Pharmacol Ther . 1991; 5:151-60. [PubMed 1716168]

30. Angus P, Snook JA, Reid M et al. Oral fluticasone propionate in active distal ulcerative colitis. Gut . 1992; 33:711-4. [PubMed 1612492][PubMedCentral]

31. Carpani de Kaski M, Peters AM, Lavender JP et al. Fluticasone propionate in Crohn's disease. Gut . 1991; 32:657-61. [PubMed 2060874][PubMedCentral]

32. Haynes RC Jr. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:1431-1462.

33. Darnell R, Pecoud A, Richards DH. A double-blind comparison of fluticasone propionate aqueous nasal spray, terfenadine tablets, and placebo in the treatment of patients with seasonal allergic rhinitis to grass pollen. Clin Exp Allergy . 1994; 24:1144-50. [PubMed 7889428]

34. Belling U. Once daily treatment with fluticasone propionate aqueous nasal spray or astemizole tablets for seasonal rhinitis. Clin Exp Allergy . 1990; 20(Suppl 1):98.

35. Meltzer EO, Orgel HA, Rogenes PR et al. Nasal cytology in patients with allergic rhinitis: effects of intranasal fluticasone propionate. J Allergy Clin Immunol . 1994; 94:708-15. [PubMed 7930304]

36. Dahl R, Lundback B, Malo JL et al. A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. Chest . 1993; 104:1352-8. [PubMed 8222787]

37. Chervinsky P, van As A, Bronsky EA et al. Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. J Allergy Clin Immunol . 1994; 94:676-83. [PubMed 7930300]

38. Wolthers OD, Pedersen S. Short term growth during treatment with inhaled fluticasone propionate and beclomethasone diproprionate. Arch Dis Child . 1993; 68:673-6. [PubMed 8323338][PubMedCentral]

39. Barnes NC, Marone G, Di Maria GU et al. A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. Eur Respir J . 1993; 6:877-85. [PubMed 8339809]

40. Ward C, Booth H, Gardiner PV et al. The effect of high dose inhaled fluticasone propionate (FP) on broncho alveolar lavage (BAL) lymphocyte subsets from asthmatic subjects. Eur Respir J . 1993; 6(Suppl 17):585S.

41. Noonan MJ, Chervinsky P, Weisberg SC et al. Fluticasone propionate (FP) aerosol in the treatment of oral corticosteroid dependent asthmatics. Eur Respir J . 1993; 6(Suppl 17):585S.

42. Harding SM, Felstead S. A comparison of the tolerance and systemic effects of fluticasone propionate (FP) and beclomethasone dipropionate (BDP) in healthy volunteers. Eur Respir J . 1988; 1(Suppl 2):196S.

43. Price JF. Comparative data in childhood asthma. Eur Respir J . 1992; 5(Suppl 15):326S.

44. Pauli G, Dietemann A, Desfougères JL et al. Fluticasone propionate is more effective and as safe as nedocromil in the treatment of moderate asthma. Eur Respir J . 1993; 6(Suppl 17):586S.

45. MacKenzie CA, Wales JKH. Clinical experience with inhaled fluticasone propionate-childhood growth. Eur Respir J . 1993; 6(Suppl 17):262S.

46. Nathan RA, Bronsky EA, Fireman P et al. Once daily fluticasone propionate aqueous nasal spray is an effective treatment for seasonal allergic rhinitis. Ann Allergy . 1991; 67:332-8. [PubMed 1897811]

47. Mitchison HC, Al Mardini H, Gillespie S et al. A pilot study of fluticasone propionate in untreated coeliac disease. Gut . 1991; 32:260-5. [PubMed 1901562][PubMedCentral]

48. Glaxo. Product information form for American hospital formulary service: Flonase^® (fluticasone propionate nasal spray). Research Triangle Park, NC; 1994 Nov.

49. Scadding GK, Darby YC, Austin CE. Effect of short-term treatment with fluticasone propionate nasal spray on the response to nasal allergen challenge. Br J Clin Pharmacol . 1994; 38:447-51. [PubMed 7893587][PubMedCentral]

50. Feather I, Wilson S, Smith S et al. The accumulation of mast cells and eosinophils in the nasal mucosa in seasonal allergic rhinitics during natural pollen exposure, is inhibited by prophylactic fluticasone propionate aqueous nasal spray. Am Rev Respir Dis . 1992; 145:A853. [PubMed 1554222]

51. Banov CH, Woehler TR, LaForce CF et al. Once daily intranasal fluticasone propionate is effective for perennial allergic rhinitis. Ann Allergy . 1994; 73:240-6. [PubMed 8092559]

52. Grossman J, Banov C, Bronsky EA. Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis. Pediatrics . 1993; 92:594-9. [PubMed 8414833]

53. Fluticasone Propionate Collaborative Pediatric Working Group. Treatment of seasonal allergic rhinitis with once-daily intranasal fluticasone propionate therapy in children. J Pediatr . 1994; 125:628-34. [PubMed 7931889]

54. LaForce C, Dockhorn R, Findlay S et al. Fluticasone propionate treatment for seasonal allergic rhinitis is safe and effective in adults and adolescents. J Allergy Clin Immunol . 1991; 87:153.

55. Dockhorn RJ, Paull BR, Meltzer EO et al. Once-versus twice-daily fluticasone propionate aqueous nasal spray for seasonal allergic rhinitis. Am J Rhinology . 1993; 7:77-83.

56. Hampel F, Howland W, Martin B et al. The efficacy of fluticasone propionate aqueous nasal spray for treatment of rhinitis is dependent on topical application. J Allergy Clin Immunol . 1994; 93:165.

57. Selner J, Banov C, Boltansky H et al. Fluticasone propionate aqueous nasal spray effectively treats perennial non-allergic rhinitis. J Allergy Clin Immunol . 1994; 93:165.

58. Lemanske R, Dunn K, Galant S et al. Fluticasone propionate aqueous nasal spray is more effective than astemizole in the treatment of seasonal allergic rhinitis. J Allergy Clin Immunol . 1994; 93:165.

59. Boner A, Sette L, Martinati L et al. The efficacy and tolerability of fluticasone propionate aqueous nasal spray in children with seasonal allergic rhinitis. Allergy . 1995; 50:498-505. [PubMed 7573843]

60. Peroni D, Feather I, Wilson S et al. Fluticasone propionate aqueous nasal spray alleviates the symptoms of perennial allergic rhinitis without changing the mucosal inflammatory cell profile. J Allergy Clin Immunol . 1993; 91:260.

61. Feather I, Peroni D, Wilson S et al. Prophylactic fluticasone propionate aqueous nasal spray (FP) suppresses eosinophil and mast cell accumulation in seasonal allergic rhinitis without altering local T lymphocyte populations. J Allergy Clin Immunol . 1993; 91:260.

62. Scadding GK, Lund VJ, Holmstrom M et al. Clinical and physiological effects of fluticasone propionate aqueous nasal spray in the treatment of perennial rhinitis. Rhinology . 1991; (Suppl 11):37-43. [PubMed 1888556]

63. Meltzer EO, Jalowayski AA, Field EA et al. Intranasal fluticasone propionate reduces histamine and tryptase in the mucosa of allergic rhinitis patients. J Allergy Clin Immunol . 1993; 91:298.

64. Pedersen B, Dahl R, Lindqvist N et al. Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma. Allergy . 1990; 45:451-6. [PubMed 2244675]

65. Glaxo Dermatology. Cutivate^® (fluticasone propionate) ointment, 0.005% prescribing information. Research Triangle Park, NC; 1992 Jan.

66. Glaxo Dermatology. Cutivate^® (fluticasone propionate) cream, 0.05% prescribing information. Research Triangle Park, NC; 1992 Feb.

67. Siegel SC. Topical intranasal corticosteroid therapy in rhinitis. J Allergy Clin Immunol . 1988; 81:984-91. [PubMed 2897390]

68. Davies B. A comparison of beclomethasone dipropionate and budesonide in the treatment of asthma. Br J Clin Pract . 1993; 47:87-93. [PubMed 8334070]

69. Anon. Fluticasone propionate nasal spray for allergic rhinitis. Med Lett Drugs Ther . 1995; 37:5-6. [PubMed 7815981]

70. Hill D, Connolly D, Vorath J. Beclomethasone dipropionate aerosol in the treatment of children with severe perennial rhinitis. Med J Aust . 1978; 2:603-4. [PubMed 366350]

71. Austen KF. Diseases of immediate type hypersensitivity. In: Isselbacher KJ, Braunwald E, Wilson JD et al, eds. Harrision's principles of internal medicine. 13th ed. New York: McGraw Hill, Inc.; 1994:1630,1638.

72. Anon. Histamine H₁-receptor antagonists. In: Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 30th ed. London: The Pharmaceutical Press; 1993:926-30.

73. Payton KB, Hebert J, Clarke KD. Assessing and treating rhinits: a practical guide for Canadian physicians. CMAJ . 1994; 151(Suppl):5-27.

74. May JR, Guill MF. Allergic rhinitis. In: DiPiro JT, Talbert RL, Hayes PE et al, eds. Pharmacotherapy a pathophysiologic approach. 2nd ed. New York: Elsevier; 1992:1377-86.

75. Kaliner M, Eggleston PA, Mathews KP. Rhinitis and asthma. JAMA . 1987; 258:2851-73. [PubMed 2889834]

76. Knight A. The role of levocabastine in the treatment of allergic rhinoconjunctivitis. Br J Clin Pract . 1994; 48:139-43. [PubMed 7913336]

77. Welch MJ. Topical nasal steroids for allergic rhinitis. West J Med . 1993; 158:616-7. [PubMed 8337862][PubMedCentral]

78. Wood S. Allergic rhinitis and hayfever. Practitioner . 1992; 236:440-7. [PubMed 1360654]

79. Mabry RL. Topical pharmacotherapy for allergic rhinitis: new agents. South Med J . 1992; 85:149-54. [PubMed 1738880]

80. Hide W. Clinical allergy—state of the art. Br J Clin Pract . 1990; 44:85-7. [PubMed 2188686]

81. Sutherland DC. Antihistamine agents: new options or just more drugs? Med J Aust . 1989; 151:158-62. (IDIS 261855)

82. Dahl MGC. Hazards of topical steroid therapy. Adv Drug React Bull . 1985; Dec:428-31.

83. Anon. Avoiding eye damage from topical corticosteroids. Drug Ther Bull . 1987; 25:29-30. [PubMed 3582180]

84. Fraunfelder FT, Meyer SM. Posterior subcapsular cataracts associated with nasal or inhalation corticosteroids. Am J Ophthalmol . 1990; 109:489-90. [PubMed 2330959]

85. Sly RM, Kemp JP, and the American Academy of Allergy and Immunology Committee on Drugs. The use of antihistamines in patients with asthma. J Allergy Clin Immunol . 1988; 82:481-2. [PubMed 2902113]

86. Astra. Rhinocort^® (budesonide) nasal inhaler prescribing information. Westborough, MA; 1994 Jun.

87. Anon. Corticosteroids. In: Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 30th ed. London: The Pharmaceutical Press; 1993:712-40.

88. Abzug MJ, Cotton MF. Severe chickenpox after intranasal use of corticosteroids. J Pediatr . 1993; 123:577-9. [PubMed 8410510]

89. Jones JF. FDA varicella warning: the issues. Pediatrics . 1992; 90:479-81.

90. Anon. Prednisone: fetal risk summary. In: Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs in pregnancy and lactation. 2nd ed. Baltimore: Williams & Wilkins; 1986:366-7p.

91. Hilman BC. Bronchodilators and antiallergy drugs. In: Wilson JT, ed. Drugs in breast milk. Sydney: ADIS Health Science Press; 1981:53-60.

92. Ramsdale EH, Kline PA. Comparison of once daily treatment with an antihistamine (loratadine) and topical steroid (fluticasone propionate) during the ragweed pollen season. J Allergy Clin Immunol . 1991; 87:298.

93. Johannessen TA. A comparison of fluticasone propionate, flunisolide and placebo in patients with seasonal allergic rhinitis to birch pollen—a multicentre trial. Clin Exp Allergy . 1990; 20(Suppl 1):102.

94. Prahl P, Wilken-Jensen K, Mygind N. Beclomethasone dipropionate aerosol in treatment of hay fever in children. Arch Dis Child . 1975; 50:875-8. [PubMed 2110][PubMedCentral]

95. Vervloet D, Charpin D, Desfougeres JL. Fluticasone propionate aqueous nasal spray versus cetirizine (C) in seasonal rhinitis. Eur Resp J . 1991; 4(Suppl 14):436S.

96. Naclerio RM, Mygind N. Intranasal steroids. In: Mygind N, Naclerio RM, eds. Allergic and non-allergic rhinitis clinical aspects. 1st ed. Copenhagen: Munksgaard; 1993:114-22.

97. Middleton E Jr. Systemic steroids. In: Mygind N, Naclerio RM, eds. Allergic and non-allergic rhinitis clinical aspects. 1st ed. Copenhagen: Munksgaard; 1993:111-3.

98. Deltasone^® (prednisone) tablets prescribing information. In: Physicians' desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:2444-6.

99. Anon. Revised label warns of severe viral problems with corticosteroids. FDA Med Bull . 1991 Dec; 21:3.

100. Peterson F (US Food and Drug Administration). Corticosteroid drugs and chickenpox. Rockville, MD; 1991 Dec 2.

101. Corticosteroid interactions. In: Hansten PD, Horn Jr. Drug Interactions and Updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:559-60.

102. Gregg I. The importance of patient education in the use of inhaled steroids. In: Mygind N, Clark TJH eds. Topical steroid treatment for asthma and rhinitis. London: Baillière Tindall; 1980:137-42.

103. Shaw RJ. Pharmacology of fluticasone propionate. Respir Med . 1994; 88(Suppl A):5-8. [PubMed 7972993]

104. Sahay JN, Ibrahim NBN, Chatterjee SS et al. Long-term study of flunisolide treatment in perennial rhinitis with special reference to nasal mucosal histology and morphology. Clin Allergy . 1980; 10:451-7. [PubMed 6778629]

105. Mygind N, Clark TJH. Safety and topical side-effects. In: Mygind N, Clark TJH eds. Topical steroid treatment for asthma and rhinitis. London: Baillière Tindall; 1980:171-9.

106. Wales JKH, Milner RDG. Knemometry in assessment of linear growth. Arch Dis Child . 1987; 62:166-71. [PubMed 3827294][PubMedCentral]

107. Hermanussen M, Geiger-Benoit K, Burmeister J et al. Can the knemometer shorten the time for growth rate assessment? Acta Paediatr Scand . 1987; 337(Suppl):30-6.

108. Li J, Lyles K, Halstenson C et al. Long-term safety study of fluticasone propionate aqueous nasal spray. Ann Allergy Asthma Immunol . 1995; 74:58.

109. Glaxo Inc. Research Triangle Park, NC: Product information for fluticasone propionate. Undated.

110. Glaxo Inc. Research Triangle Park, NC: Personal communication.

111. Glaxo Inc. Research Triangle Park, NC: Toxicology studies summary information for fluticasone propionate. Undated.

112. Benincasa C, Lloyd RS. Evaluation of fluticasone propionate aqueous nasal spray taken alone and in combination with cetirizine in the prophylactic treatment of seasonal allergic rhinitis. Drug Invest . 1994; 8:225-33.

113. Reviewers' comments (personal observations).

114. Nathan RA. The efficacy of fluticasone propionate aqueous nasal spray in the treatment of allergic rhinitis. Todays Ther Trends . 1995; 12:119-34.

115. Syntex Laboratories, Inc. Nasalide^® (flunisolide) nasal solution 0.025% prescribing information. In: Physicians' desk reference. 49th ed. Montvale, NJ: Medical Economics Company Inc; 1995:2480-1.

116. Rak S, Jacobson MR, Sudderick RM et al. Influence of prolonged treatment with topical corticosteroid (fluticasone propionate) on early and late phase nasal responses and cellular infiltration in the nasal mucosa after allergen challenge. Clin Exp Allergy . 1994; 24:930-9. [PubMed 7842362]

117. Högger P, Rohdewald P. Binding kinetics of fluticasone propionate to the human glucocorticoid receptor. Steroids . 1994; 59:597-602. [PubMed 7878687]

118. Pichler WJ, Klint T, Blaser M et al. Clinical comparison of systemic methylprednisolone acetate versus topical budesonide in patients with seasonal allergic rhinitis. Allergy . 1988; 43:87-92. [PubMed 3364627]

119. Clissold SP, Heel RC. Budesonide: a preliminary review of its pharmacodynamic properties and therapeutic efficacy in asthma and rhinitis. Drugs . 1984; 28:485-518. [PubMed 6394263]

120. Cockcroft DW, Hargreave FE, Dolovich J. Intranasal beclomethasone dipropionate in rhinitis. In: Mygind N, Clark TJH eds. Topical steroid treatment for asthma and rhinitis. London: Baillière Tindall; 1980:143-53.

121. Szefler SJ. Glucocorticoid therapy for asthma: clinical pharmacology. J Allergy Clin Immunol . 1991; 88:147-65. [PubMed 1880315]

122. Jordana G, Dolovich J, Briscoe MP et al. Intranasal fluticasone propionate versus loratadine in the treatment of adolescent patients with seasonal allergic rhinitis. J Allergy Clin Immunol . 1996; 97:588-95. [PubMed 8621843]

123. Ngamphaiboon J, Thepchatri A, Chatchtatee P et al. Fluticasone propionate aqueous nasal spray treatment for perennial allergic rhinitis in children. Ann Allergy Asthma Immunol . 1997; 78:479-84. [PubMed 9164361]

124. Richards DH, Milton CM. Fluticasone propionate aqueous nasal spray: a well-tolerated and effective treatment for children with perennial rhinitis. Pediatr Allergy Immunol . 1996; 7:35-43. [PubMed 8792382]

125. GlaxoSmithKline. Flovent^® Rotadisk^® (fluticasone propionate) inhalation powder 50, 100, and 250 mcg prescribing information. Research Triangle Park, NC; 2001 Sep.

126. Pedersen S. Assessing the effect of intranasal steroids on growth. J Allergy Clin Immunol . 2001; 108:S40-4. [PubMed 11449205]

127. Skoner D. Update of growth effects of inhaled and intranasal corticosteroids. Cur Opin Allergy Clin Immunol . 2002; 2:7-10.