HPA axis safety of fluticasone furoate nasal spray once daily in children with perennial allergic rhinitis

Abstract

The effects of intranasal corticosteroids (INSs) on the hypothalamic-pituitary-adrenal (HPA) axis should be assessed for any to be marketed INS. The objective of this study was to assess the effects of fluticasone furoate nasal spray (FFNS) on cortisol production (as a measure of HPA axis function) following 6 wk of treatment with FFNS 110 microg once daily (QD) compared with placebo in pediatric patients with perennial allergic rhinitis (PAR). In this double-blind, parallel-group study, patients (n = 112) aged 2-11 yr with a 1-yr history of PAR (6 months for patients aged 2-3 yr) were randomized in a 1:1 ratio to either placebo or FFNS. Serum cortisol (SC) concentrations and urinary cortisol (UC) excretion were measured over a 24-h period at the randomization (baseline) and final treatment (week 6) visits for HPA axis evaluation in a domiciled environment (overnight in the clinic). Plasma samples were collected for FFNS at several time points over the 24 h after the final dose for pharmacokinetic analyses. FFNS was non-inferior to placebo with respect to change from baseline (expressed as a ratio) in 24-h SC weighted mean. The lower limit of the two-sided 95% confidence interval (CI) for the treatment ratio was greater than the pre-specified non-inferiority margin of 0.8 (treatment ratio = 0.97, 95% CI 0.88-1.07). UC excretion over 24 h at baseline and end of treatment was similar between treatment groups; no patients had 24-h excretion levels below normal range after 6 wk of treatment. Plasma concentrations of FFNS were generally non-quantifiable (<10 pg/ml). Results of the current study indicate that FFNS 110 microg QD has no significant effect on HPA axis function in 2- to 11-yr-old pediatric patients with PAR.

Fluticasone furoate nasal spray: Profile of an enhanced-affinity corticosteroid in treatment of seasonal allergic rhinitis

“…The risk of intranasal corticosteroid-associated hypothalamic-pituitary-adrenal axis suppression is low compared with that associated with the more bioavailable oral corticosteroids 48. Potential effects of fluticasone furoate nasal spray on hypothalamic-pituitary-adrenal axis function have been assessed in several studies, none of which demonstrated an effect of the drug 18,49,50…”

Fluticasone furoate induced iatrogenic Cushing syndrome in a pediatric patient receiving anti-retroviral therapy

“…Fluticasone furoate is an intranasal steroid spray for the treatment of allergic rhinitis (2). The furoate ester renders it poorly absorbable in the gastrointestinal tract and causes the minimal amount that is absorbed to be rapidly metabolized by the liver (1).…”

“…Given these properties, adrenal suppression should be expected only when the bioavailable dose is such that circulating levels become high enough to interfere with the hypothalamic–pituitary axis. Indeed, clinical trials have shown that adrenal suppression was absent in children treated with fluticasone furoate, although it must be said that all trials in which adrenal function in children was addressed were based on the lowest recommended dose (2). …”

“…Given the use of an intranasal steroid, we determined that the biochemical phenotype best fitted with an iatrogenic Cushing syndrome, even though this was described not to be associated with fluticasone furoate use (2). Unfortunately, serum concentration of fluticasone furoate analysis was not available at the time of diagnosis.…”

“…Fluticasone furoate treatment is described to have no negative impact on the hypothalamic–pituitary–adrenal (HPA) axis as the systemic bioavailability is low (1). However, all clinical trials regarding adrenal function in patients using fluticasone furoate have been performed in patients using a 1 dose/day regimen (2), whereas a 2 dose/day is still within the recommended dose.…”