Fluticasone (Flonase®)
Cutivate®, Flonase®, Flovent® | Flovent® HFA
Classification:
Dermatological Agents
Topical Antiinflammatory Agents
Hormones and Hormone Modifiers
Adrenal Agents
Respiratory Agents
Respiratory Antiinflammatory Agents
Description: Fluticasone is a medium-potency synthetic corticosteroid. It is used topically to relieve the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and psoriasis, intranasally for the management of symptoms of allergic and non-allergic rhinitis, and by oral inhalation for the treatment of asthma. The anti-inflammatory activity of topical fluticasone is about 13 times as potent as triamcinolone acetonide, 9 times as potent as fluocinolone acetonide, 3 times as potent as betamethasone valerate, and 2 times as potent as beclomethasone dipropionate. When first released as a treatment for asthma, fluticasone was reported to be safer than other marketed inhaled corticosteroids, however, this observation was based on maximal dosages of 200 mcg/day. Higher daily doses of inhaled fluticasone used in clinical practice have been reported to cause a significant reduction in adrenal cortisol production. Fluticasone inhalations are also used clinically in certain patients with chronic obstructive pulmonary disease (COPD). Fluticasone is commercially available as fluticasone propionate and was originally approved by the FDA in December 1990. Based on information indicating that chlorofluorocarbons (CFCs) are ozone-depleting substances (ODSs), many manufacturers have reformulated their original inhalational aerosols by substituting hydrofluoroalkanes (HFAs) for CFCs as the aerosol propellant. Flovent® inhalational aerosol was discontinued in February 2005. Flovent® HFA (a chlorofluorocarbon-free metered-dose inhaler) was approved by the FDA in May 2004.
Mechanism of Action: Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme which causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.
In the treatment of asthma, orally inhaled corticosteroids block the late phase allergic response to allergens. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV1, peak-flow rate, and respiratory symptoms. Since corticosteroid effects take several hours to days to become clinically noticeable, they are ineffective for primary treatment of severe acute bronchospastic attacks or for status asthmaticus. Inhaled corticosteroids have no bronchodilatory properties.
Cutivate Cream (Cream 0.05 %)
In the treatment of allergies, intranasal fluticasone reduces allergic responses of several cell types (e.g., mast cells and eosinophils) involved in the allergic response by the same cellular mechanism as the topical corticosteroids. Clinically, symptoms such as rhinorrhea and postnasal drip, nasal congestion, sneezing, and pharyngeal itching are reduced.
Pharmacokinetics: Fluticasone propionate is administered either by oral inhalation, or by topical administration to the skin or nasal mucosa. Absorption following topical administration to the skin is usually minimal and depends on such factors as the vehicle and the integrity of the epidermis. Due primarily to absorption from the lung, oral inhalation aerosol usually results in a systemic bioavailability of about 30% of the delivered dose. The bioavailability of the oral inhalation powder is roughly 14%. Intranasal fluticasone propionate has an absolute bioavailability of < 2%. Based on studies using intravenous fluticasone propionate, distribution is rapid because of high lipid solubility and tissue binding. Protein binding averages about 91%. The drug is weakly and reversibly bound to erythrocytes and is not significantly bound to human transcortin.
Metabolism of fluticasone propionate occurs via hepatic cytochrome P450 3A4. A 17beta-carboxylic acid derivative is the only metabolite detected in man. This metabolite is significantly less active than fluticasone propionate. Excretion is primarily in the feces as parent drug and metabolites. Less than 5% of a dose is excreted in the urine as metabolites. The terminal elimination half-life is approximately 7.8 hours.
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[ Revised 4/21/2006 1:50:00 PM ]
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