NASONEX Nasal Spray, 50 mcg is a corticosteroid demonstrating anti-inflammatory properties. The precise mechanism of corticosteroid action on allergic rhinitis is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation.

In two clinical studies utilizing nasal antigen challenge, NASONEX Nasal Spray, 50 mcg decreased some markers of the early- and late-phase allergic response. These observations included decreases (vs placebo) in histamine and eosinophil cationic protein levels, and reductions (vs baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins. The clinical significance of these findings is not known.

The effect of NASONEX Nasal Spray, 50 mcg on nasal mucosa following 12 months of treatment was examined in 46 patients with allergic rhinitis. There was no evidence of atrophy and there was a marked reduction in intraepithelial eosinophilia and inflammatory cell infiltration (eg, eosinophils, lymphocytes, monocytes, neutrophils, and plasma cells).

Pharmacokinetics

Absorption: Mometasone furoate monohydrate administered as a nasal spray is virtually undetectable in plasma from adult and pediatric subjects despite the use of a sensitive assay with a lower quantitation limit (LOQ) of 50 pcg/mL.

Distribution: The in vitro protein binding for mometasone furoate was reported to be 98% to 99% in concentration range of 5 to 500 ng/mL.

Metabolism: Studies have shown that any portion of a mometasone furoate dose which is swallowed and absorbed undergoes extensive metabolism to multiple metabolites. There are no major metabolites detectable in plasma. Upon in vitro incubation, one of the minor metabolites formed is 6β-hydroxy-mometasone furoate. In human liver microsomes, the formation of the metabolite is regulated by cytochrome P-450 3A4 (CYP3A4).

Elimination: Following intravenous administration, the effective plasma elimination half-life of mometasone furoate is 5.8 hours. Any absorbed drug is excreted as metabolites mostly via the bile, and to a limited extent, into the urine.

Special Populations

The effects of renal impairment, hepatic impairment, age, or gender on mometasone furoate pharmacokinetics have not been adequately investigated.

Pharmacodynamics

Four clinical pharmacology studies have been conducted in humans to assess the effect of NASONEX Nasal Spray, 50 mcg at various doses on adrenal function. In one study, daily doses of 200 and 400 mcg of NASONEX Nasal Spray, 50 mcg and 10 mg of prednisone were compared to placebo in 64 patients with allergic rhinitis. Adrenal function before and after 36 consecutive days of treatment was assessed by measuring plasma cortisol levels following a 6-hour Cortrosyn (ACTH) infusion and by measuring 24-hour urinary-free cortisol levels. NASONEX Nasal Spray, 50 mcg, at both the 200- and 400-mcg dose, was not associated with a statistically significant decrease in mean plasma cortisol levels post-Cortrosyn infusion or a statistically significant decrease in the 24-hour urinary-free cortisol levels compared to placebo. A statistically significant decrease in the mean plasma cortisol levels post-Cortrosyn infusion and 24-hour urinary-free cortisol levels was detected in the prednisone treatment group compared to placebo.

A second study assessed adrenal response to NASONEX Nasal Spray, 50 mcg (400 and 1600 mcg/day), prednisone (10 mg/day), and placebo, administered for 29 days in 48 male volunteers. The 24-hour plasma cortisol area under the curve (AUC_0-24), during and after an 8-hour Cortrosyn infusion and 24-hour urinary-free cortisol levels were determined at baseline and after 29 days of treatment. No statistically significant differences of adrenal function were observed with NASONEX Nasal Spray, 50 mcg compared to placebo.

A third study evaluated single, rising doses of NASONEX Nasal Spray, 50 mcg (1000, 2000, and 4000 mcg/day), orally administered mometasone furoate (2000, 4000, and 8000 mcg/day), orally administered dexamethasone (200, 400, and 800 mcg/day), and placebo (administered at the end of each series of doses) in 24 male volunteers. Dose administrations were separated by at least 72 hours. Determination of serial plasma cortisol levels at 8 AM and for the 24-hour period following each treatment were used to calculate the plasma cortisol area under the curve (AUC_0-24). In addition, 24-hour urinary-free cortisol levels were collected prior to initial treatment administration and during the period immediately following each dose. No statistically significant decreases in the plasma cortisol AUC, 8 AM cortisol levels, or 24-hour urinary-free cortisol levels were observed in volunteers treated with either NASONEX Nasal Spray, 50 mcg or oral mometasone, as compared with placebo treatment. Conversely, nearly all volunteers treated with the three doses of dexamethasone demonstrated abnormal 8 AM cortisol levels (defined as a cortisol level < 10 mcg/dL), reduced 24-hour plasma AUC values, and decreased 24-hour urinary-free cortisol levels, as compared to placebo treatment.

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