In short-term trials (2-6 weeks duration) overall incidence of adverse reactions was low and comparable to placebo^*1

Adverse Reaction	ZETONNA 74 mcg once daily (n=884)	Placebo (n=892)
Nasal discomfort†	3.2%	1.8%
Headache	3.1%	1.2%
Epistaxis	2.9%	2.7%

*Adverse reactions that occurred with a frequency of ≥2.0% and greater than placebo from 4 controlled clinical trials 2 to 6 weeks in duration in patients aged 12 years and older with SAR or PAR.

^†Nasal discomfort includes both nasal discomfort and instillation site discomfort.

In 3 short-term trials and the first 6 weeks of a long-term trial, nasal septal perforations were reported in 2 of 884 patients treated with ZETONNA compared with none of 892 patients treated with placebo¹. Both perforations occurred in 2-week SAR trials while none occurred in the longer term trials.

ZETONNA exhibited low discontinuation rates dues to adverse reactions in both SAR and PAR (first 6 weeks) studies vs placebo in the short-term

• ZETONNA (1.2%) vs placebo (1.3%)^{1, 6}

In a 6-month safety trial of patients with PAR

• Discontinuation rates due to local adverse reactions were (1.7%) for ZETONNA vs (0.7%) for placebo¹
• No patients experienced a nasal septal perforation during the long-term trial¹
• Nasal discomfort (5.7%) and epistaxis (11.4%) were more frequently observed in patients treated with ZETONNA compared with short-term trials¹

ZETONNA had no apparent effect on HPA-axis function

• In a 6-week, randomized, double-blind, placebo-controlled trial in adolescents and adults with PAR, daily doses of 148 mcg and 282 mcg of ZETONNA were compared to placebo nasal aerosol. Dexamethasone 6 mg was used as an active control during the last 4 days of the trial. Adrenal function was assessed by 24-hour serum cortisol AUC before and after the treatment
• The difference from placebo for the change from baseline in serum cortisol AUC (0-24) was -2.4 mcg·hour/dL (95% CI: -15.1, 10.2) and -0.5 mcg·hour/dL (95% CI: -13.9, 13.0) for 148-mcg/day and 282-mcg/day treatments, respectively
• The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency and symptoms of corticosteroid withdrawal. Patients transferred to topical steroids after a prolonged period of treatment with a systemic corticosteroid should be carefully monitored. Rapid decreases in systemic corticosteroid dosages in patients taking them for diseases such as asthma or other conditions may cause a severe exacerbation of their symptoms
• Before prescribing ZETONNA conduct a nasal examination to ensure that patients are free of nasal disease other than allergic rhinitis. Periodically conduct nasal examinations during treatment. If an adverse reaction (eg, erosion, ulceration, perforation) is noted, discontinue ZETONNA. Counsel patients that ZETONNA should not be sprayed directly on the nasal septum

Formulation Characteristics