The safety and effectiveness for seasonal and perennial allergic rhinitis in pediatric patients 12 years of age and older have been established. Use of ZETONNA for this indication is supported by evidence from placebo-controlled, double-blind trials in patients 12 years and older with allergic rhinitis [see Clinical Studies (14)]. 

The safety and effectiveness of ZETONNA have not been established in pediatric patients younger than 12 years of age. 

Effectiveness was not demonstrated for ZETONNA in pediatric patients 6 through 11 years of age. These patients were evaluated in 2 randomized, double blind, parallel placebo-controlled clinical trials in 1693 pediatric patients with allergic rhinitis. Of the 2 trials, 1 was 2 weeks in duration and evaluated the efficacy of 2 doses of ZETONNA (37 mcg and 74 mcg once daily) in 847 patients with seasonal allergic rhinitis. The second clinical trial was 12 weeks in duration and evaluated the efficacy of 2 doses of ZETONNA (37 mcg and 74 mcg once daily) in 846 patients with perennial allergic rhinitis. The trials were similar in design to the trials conducted in pediatric patients 12 years and older and adults. The primary efficacy endpoint was the difference from placebo in the change from baseline of the average morning and evening reflective total nasal symptom scores (rTNSS) averaged over 2 weeks of treatment in the seasonal allergic rhinitis trial and over the first 6 weeks of treatment in the perennial allergic rhinitis trial. In the 2-week trial in patients with seasonal allergic rhinitis, treatment with ZETONNA at either dose failed to demonstrate efficacy. In the 12-week trial in patients with perennial allergic rhinitis, both ZETONNA 37 mcg and 74 mcg once daily demonstrated significant improvement in rTNSS compared to placebo with treatment differences of 0.59 (95% CI: 0.23, 0.95) and 0.47 (95% CI: 0.11, 0.83), respectively. 

The effect of ZETONNA on the HPA axis was evaluated in one placebo-controlled clinical study of 6 weeks in duration in children 6 to11 years of age with perennial allergic rhinitis [see Clinical Pharmacology (12.2)].

Studies in pediatric patients under 6 years of age have not been conducted.

Effect on Growth

Controlled clinical trials have shown that nasal corticosteroids may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA)-axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA-axis function. The long-term effects of this reduction in growth velocity associated with nasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with nasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving nasal corticosteroids, including ZETONNA, should be monitored routinely (e.g., via stadiometry). A 52-week, multi-center, double-blind, randomized, placebo-controlled parallel-group trial was conducted to assess the effect of orally inhaled ciclesonide (ALVESCO® Inhalation Aerosol) on growth rate in 609 pediatric patients with mild persistent asthma, aged 5 to 8.5 years. Treatment groups included orally inhaled ciclesonide 40 mcg or 160 mcg or placebo given once daily. Growth was measured by stadiometer height during the baseline, treatment and follow-up periods. The primary comparison was the difference in growth rates between ciclesonide 40 and 160 mcg and placebo groups. Conclusions cannot be drawn from this trial because compliance could not be assured. Ciclesonide blood levels were also not measured during the one-year treatment period. There was no difference in efficacy measures between the placebo and the orally inhaled ciclesonide (ALVESCO® Inhalation Aerosol) groups.

The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of safe and effective noncorticosteroid treatment alternatives. To minimize the systemic effects of nasal corticosteroids, each patient should be titrated to the lowest dose that effectively controls his/her symptoms.

The potential for ZETONNA to cause growth suppression in susceptible patients or when given at higher than recommended dosages cannot be ruled out.