During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. In a placebo-controlled, crossover study in 8 healthy volunteers, coadministration of a single dose of orally inhaled fluticasone propionate (1,000 mcg) with multiple doses of ketoconazole (200 mg) to steady state resulted in increased mean plasma fluticasone propionate exposure, a reduction in plasma cortisol AUC, and no effect on urinary excretion of cortisol. Caution should be exercised when FLOVENT Inhalation Aerosol is coadministered with ketoconazole and other known potent cytochrome P450 3A4 inhibitors. Carcinogenesis, Mutagenesis, Impairment of Fertility Fluticasone propionate demonstrated no tumorigenic potential in studies of oral doses up to 1,000 mcg/ kg (approximately 2 times the maximum human daily inhalation dose based on mcg/ m 2 ) for 78 weeks in the mouse or inhalation of up to 57 mcg/ kg (approximately 1/ 4 the maximum human daily inhalation dose based on mcg/ m 2 ) for 104 weeks in the rat. Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the mouse micronucleus test when administered at high doses by the oral or subcutaneous routes. Furthermore, the compound did not delay erythroblast division in bone marrow. No evidence of impairment of fertility was observed in reproductive studies conducted in rats dosed subcutaneously with doses up to 50 mcg/ kg (approximately 1/ 4 the maximum human daily inhalation dose based on mcg/ m 2 ) in males and females. However, prostate weight was significantly reduced in rats. | ||||
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