Long-term safety of fluticasone furoate nasal spray in adults and adolescents with perennial allergic rhinitis.

BACKGROUND: Fluticasone furoate is a novel-enhanced affinity glucocorticoid and its long-term safety must be assessed. This study was designed to assess the safety and tolerability of 12-month intranasal administration of fluticasone furoate in adult and adolescent patients with perennial allergic rhinitis (PAR). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 806 patients with PAR were randomized to once daily (od) fluticasone furoate nasal spray 110 microg (n = 605) or vehicle placebo nasal spray (n = 201) for 12 months, following a 7- to 14-day screening period. Safety was assessed by monitoring adverse events (AEs), 24-h urinary cortisol excretion, nasal and ophthalmic examinations, electrocardiograms and clinical laboratory tests. Plasma concentrations of fluticasone furoate were determined from blood samples. RESULTS: Fluticasone furoate was well tolerated. The incidence of most AEs was similar to that observed with placebo, with the exception of epistaxis, which was more frequently reported on active treatment. There were no clinically meaningful differences between fluticasone furoate and placebo in terms of safety assessments, including mean changes in ophthalmic parameters and 24-h urine cortisol excretion. Plasma concentrations of fluticasone furoate were not quantifiable in the majority of patients following intranasal administration. CONCLUSIONS: Long-term (12-month) administration of fluticasone furoate 110 microg od revealed an AE profile typical of the intranasal corticosteroid class in both adult and adolescent patients with PAR, with no evidence of clinically relevant systemic corticosteroid exposure.

Passive smoking, allergic rhinitis and nasal obstruction in children.

Allergic rhinitis is a common cause of nasal obstruction in childhood. This prospective study looked at the effect of passive smoking on nasal obstruction in children with and without allergic rhinitis. Eighty-one children took part. Each child was asked to score his or her degree of nasal obstruction on a visual analogue scale. Exposure to passive smoking was determined subjectively using a parental questionnaire, and objectively by measuring the urinary cotinine/creatinine ratio. Results were tabulated using Microsoft Excel and analysed with SPSS statistical software. Nasal obstruction was significantly worse in children with a positive history of allergic rhinitis (p < 0.05). There was also a trend towards a higher nasal obstruction score in children without allergic rhinitis exposed to passive smoking compared to those who were not so exposed. As would be expected, nasal obstruction is worse in children with allergic rhinitis than in those without. Passive smoking tends to increase the symptom of nasal obstruction in children without allergic rhinitis.

Lack of effect of fluticasone propionate aqueous nasal spray on the hypothalamic-pituitary-adrenal axis in 2- and 3-year-old patients.

OBJECTIVE: Fluticasone propionate aqueous nasal spray (FP) at the highest recommended doses does not affect hypothalamic-pituitary-adrenal (HPA) axis function in adults or older children, but its potential effects in children younger than 4 years have not been previously studied. This randomized, double-blind, placebo-controlled study evaluated the effects of FP on HPA axis function measured by 12-hour urinary-free cortisol levels in children 2 to 3 years of age. METHODS: Patients ages 2 to 3 years with symptoms of allergic rhinitis were administered FP 200 microg/day (FP200 QD) or vehicle placebo for 6 weeks. RESULTS: The FP200 QD group (n = 33) was equivalent to the placebo group (n = 32) in mean change from baseline in the primary safety measure of 12-hour creatinine-corrected urinary-free cortisol concentration (geometric mean difference [standard error; SE] for placebo-FP200 QD = 0.96 [1.20]; 95% confidence interval 0.66, 1.39) at the end of the treatment period. The adjusted geometric mean change from baseline value was 0.98 for FP200 QD (SE = 1.14) and 0.94 for placebo (SE = 1.15); a value of 1.0 reflects no change from baseline. Cough and fever were the most common adverse events reported in either group. CONCLUSIONS: FP200 QD was equivalent to placebo with respect to effects on HPA axis function measured by 12-hour urinary-free cortisol in 2- and 3-year-old patients. FP200 QD was well-tolerated in these very young children with allergic rhinitis.

Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis. OBJECTIVE: The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test. METHODS: In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 microg once daily, FP ANS 400 microg twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily, or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol. RESULTS: There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 microg once daily or FP ANS 400 microg twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant (p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration-time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 microg twice daily and both prednisone regimens were associated with a significant (p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations. CONCLUSION: These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test.