indication

For the maintenance treatment of asthma as prophylactic therapy and for patients requiring oral corticosteroid therapy for asthma.

pharmacology

Fluticasone propionate, a medium-potency synthetic corticosteroid, is used topically to relieve inflammatory and pruritic symptoms of dermatoses and psoriasis, intranasally to manage symptoms of allergic and non-allergic rhinitis, and orally for the treatment of asthma.

mechanism of action

Binds to the glucocorticoid receptor. Unbound corticosteroids cross the membranes of cells such as mast cells and eosinophils, binding with high affinity to glucocorticoid receptors (GR). The results include alteration of transcription and protein synthesis, a decreased release of leukocytic acid hydrolases, reduction in fibroblast proliferation, prevention of macrophage accumulation at inflamed sites, reduction of collagen deposition, interference with leukocyte adhesion to the capillary wall, reduction of capillary membrane permeability and subsequent edema, reduction of complement components, inhibition of histamine and kinin release, and interference with the formation of scar tissue. In the management of asthma, the glucocorticoid receptor complexes down-regulates proinflammatory mediators such as interleukin-(IL)-1, 3, and 5, and up-regulates anti-inflammatory mediators such as IkappaB [inhibitory molecule for nuclear factor kappaB1], IL-10, and IL-12. The antiinflammatory actions of corticosteroids are also thought to involve inhibition of cytosolic phospholipase A2 (through activation of lipocortin-1 (annexin)) which controls the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

biotransformation

Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5-fluoromethyl carbothioate grouping. This transformation occurs in 1 metabolic step to produce the inactive 17-(beta)-carboxylic acid metabolite, the only known metabolite detected in man.

absorption

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier.

half life

10 hours

drug interactions

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.

Telithromycin: Telithromycin may reduce clearance of Fluticasone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Fluticasone if Telithromycin is initiated, discontinued or dose changed.

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Fluticasone propionate. Concomitant therapy should be avoided if possible.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of fluticasone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of fluticasone if voriconazole is initiated, discontinued or dose changed.