Pharmacology Update

Ciclesonide Nasal Spray (Omnaris™)

By William T. Elliott, MD, FACP, andJames Chan, PharmD, PhD; Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.

The FDA has approved a non-halogenated nasal steroid for use in pediatric patients aged 6 to 12 years and adults. Ciclesonide is a prodrug that was previously approved for adults and adolescents but was not marketed. It's to be marketed by Nycomed US Inc. as Omnaris.

Indications

Ciclesonide nasal spray is indicated for the treatment of seasonal allergic rhinitis in patients 6 years of age and older and for perennial allergic rhinitis in patients 12 years of age and older.1

Dosage

The recommended dose is 200 mcg (2 sprays [2 x 50 mcg]) in each nostril twice daily. The dose should not exceed 200 mcg daily. The pump must be primed (eight actuations) prior to initial use. If the bottle has not been used for 4 consecutive days, it should be re-primed with one spray or enough sprays to make a fine mist appear.1

Ciclesonide is available as a 12.5 g unit with 50 mcg per actuation and 120 sprays.

Potential Advantages

Ciclesonide is formulated in a hypotonic solution without benzalkonium chloride as a preservative. This may enhance drug uptake into the nasal mucosa and reduce the bitter taste.2

Potential Disadvantages

Ciclesonide is not indicated for use in children under the age of 6 years. Controlled studies have shown that intranasal steroids may cause reduction in growth velocity in pediatric patients even in the absence of hypothalamic-pituitary-adrenal axis suppression.1

Comments

Ciclesonide is a nonfluorinated corticosteroid that is the prodrug for C21-desisobutyryl-ciclesonide. It is activated by esterases in the nasal mucosa. Dose ranging studies demonstrate that the optimal dose of the drug is 200 mcg daily.1,3 This dose was shown to be statistically more efficacious than placebo in one 4-week study in adolescent and adult patients with seasonal allergic rhinitis (n = 324) and a 6-week study in patients with perennial allergic rhinitis (n = 461).1,4 The primary endpoint was the difference from placebo of the average of morning and evening nasal symptom scores. This is the sum of 4 nasal symptoms (runny nose, itchy nose, sneezing, and nasal congestion). Ciclesonide reduced baseline symptoms scores by 27% compared to 17% for placebo in seasonal allergic rhinitis over the first 2 weeks and 33% and 24% respectively in perennial allergic rhinitis over 6 weeks. Onset of action was seen within 24 to 48 hours with improvement over 1 to 2 weeks for seasonal allergic rhinitis and 5 weeks in perennial allergic rhinitis. In pediatric patients (6-11 years, n = 219), ciclesonide was significantly more effective than placebo in seasonal allergic rhinitis with a 30% reduction in baseline score compared to 25% for placebo over 2 weeks. Ciclesonide was not effective in perennial allergic rhinitis in this population.1 In a long-term study in adolescents and adults, ciclesonide was shown to be safe and effective for up to 52 weeks (n = 663).5

Patients with greater impairment in quality of life (related to activities, nasal symptoms, eye symptoms, and emotional factors) at baseline showed greater improvement with ciclesonide. A slightly higher incidence of epistaxis (10% vs 7.2%), sinusitis (9.3% vs 7.2%), and pharyngolaryngeal pain (9.3% vs 4.5%) was associated with ciclesonide compared to placebo. No clinically relevant differences were observed in morning or 24-hours urinary free cortisol levels and no tachyphylaxis was observed. Similar results were observed in pediatric patients in a 12-week study.1 There are currently no published comparative studies with other intranasal steroids. The cost was not available at the time of this review.

Clinical Implications

Intransal steroids are the mainstays in the treatment of allergic rhinitis. There are currently 7 intranasal steroid products on the market. Ciclesonide does not appear to offer any clear advantages or disadvantage over existing products. Whether the unique formulation differences (ie, hypotonic solution) offers any advantage remains to be determined.

References

1. Omnaris Product Information. Nycomed US Inc. November 2007.

2. Meltzer EO. Ann Allergy Asthma Immunol. 2007;98:12-21.

3. Ratner PH, et al. Ann Allergy Asthma Immunol. 2006;97:657-663.

4. Meltzer EO. Ann Allergy Asthma Immunol. 2007;98:175-181.

5. Chervinsky P, et al. Ann Allergy Asthma Immunol. 2007;99:69-76.