The precise mechanism through which fluticasone propionate affects rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. In 7 trials in adults, fluticasone propionate nasal spray has decreased nasal mucosal eosinophils in 66% of patients (35% for placebo) and basophils in 39% of patients (28% for placebo). The direct relationship of these findings to long-term symptom relief is not known.
Azelastine hydrochloride displayed no sensitising potential in the guinea pig. Azelastine demonstrated no genotoxic potential in a battery of in vitro and in vivo tests, nor any carcinogenic potential in rats or mice. In male and female rats, azelastine at oral doses greater than 3 mg/kg/day caused a dose-related decrease in the fertility index; no substance-related alterations were found in the reproductive organs of males or females during chronic toxicity studies, however, embryotoxic and teratogenic effects in rats, mice and rabbits occurred only at maternal toxic doses (for example, skeletal malformations were observed in rats and mice at doses of mg/kg/day).
In rabbits, fetal weight reduction and cleft palate were observed at a fluticasone propionate dose approximately times the MRHDID for adults (on a mg/m² basis at a maternal subcutaneous dose of 4 mcg/kg/day). However, no teratogenic effects were reported at fluticasone propionate doses up to approximately 20 times the MRHDID for adults (on a mg/m² basis at a maternal oral dose up to 300 mcg/kg/day). No fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration [see CLINICAL PHARMACOLOGY ].