Fluticasone, oral

Flunisolide (AeroBid, Aerospan, Nasarel) Fluticasone Furoate, Nasal (Veramyst) Fluticasone, Oral, Nasal (Flonase, Flovent, Flovent Rotadisk)... 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Children Insufficient information is available to warrant use in children younger than 6 years of age or younger than 12 years of age with fluticasone and beclomethasone. Monitor growth in children and adolescents because there is evidence that oral corticosteroids may suppress growth in a dose-related fashion, particularly in higher doses for extended periods. 

Fluticasone - Adverse reactions occurring in 3% or more of patients include headache pharyngitis nasal congestion sinusitis rhinitis upper respiratory tract infection influenza oral candidiasis diarrhea dysphonia menstrual disturbance nasal discharge allergic rhinitis fever. 

Administer by the orally inhaled route only. The maximum recommended dose of fluticasone propionate/salmeterol is 500 meg per 50 meg twice/day. 

Fluticasone, Nasal (Flonase) [Anti inflammotory/Corticos-teroid] Uses Seasonal all gic rhinitis Action Topical st oid Dose Adults Feds >12 y. 2 sprays/nostril/d Feds 4-11 y. 1-2 sprays/nostril/d Caution [C, M] Contra Primary Rx of status asthmaticus Disp Nasal spray meg SE HA, dysphonia, oral candidiasis Interactions t Effects ketoconazole EMS May... 

Presently, inhaled steroids (up to the equivalent of BDP 1000 pg/d, budesonide 800 pg/d, fluticasone 500 pg/d) should be given to patients who show an objective response to either oral or inhaled steroids (s. corticosteroid reversibility testing). For those patients who experience no symptomatic relief, the currently available evidence does not support the use of ICS for alteration of the natural history of the disease. Nevertheless, corticosteroids are effective in treating acute exacerbations in COPD and taking patients of off their ICS regimen may lead to deterioration. Oral corticosteroids (e.g. 40 mg prednisolone for ten days) are recommended for exacerbations, if... 

Prednisone Like fluticasone Like fluticasone Asthma adjunct in COPD Oral duration 12-24 hours Toxicity Multiple t see Chapter 39... 

The first inhaled glucocorticoid, beclomethasone dipropionate, revolutionized asthma therapy, when it was found that topical delivery to the lung resulted in reduced systemic side-effects (adrenal suppression, oseteoporosis and growth inhibition) typically seen with oral steroid treatments. Interestingly, a further reduction in systemic exposure was achieved with the introduction of fluticasone propionate (1). The evolution of this drug stemmed from observations with the steroid 17-carboxylates that showed that these esters were active topically when esterified, while the parent acids were inactive. Thus it was realized that enzymatic hydrolysis of the ester would lead to systemic deactivation. SAR studies led to a series of carbothioates, which were very active in vivo when topically applied to rodents, but were inactive after oral administration. It was shown that fluticasone propionate (1) underwent first pass metabolism in the liver to the corresponding inactive 173-carboxylic acid (la) (Scheme 1). This observation was... 

A 23-year-old man, with a history of asthma, house dust mite allergy, and rhinoconjunctivitis, presented with acute respiratory symptoms. He was given oral cetirizine, inhaled salmeterol, and fluticasone propionate, and oral prednisone 40 mg/day for 1 week and 20 mg/day for 1 week. His asthma recurred when prednisone was withdrawn and he took oral prednisone 60 mg/day for 1 week and 40 mg/day for 1 week. He also took montelukast 10 mg/day. He then developed severe peripheral edema with a gain in weight of 13 kg. Prednisone was withdrawn and his edema resolved. Montelukast was continued. 

The effect of inhaled ciclesonide on adrenal function has been analysed in 164 asthmatic adults in a double-blind, randomized, placebo-controlled study (40). The patients used ciclesonide 320 micrograms once daily, ciclesonide 320 micrograms twice daily, or fluticasone propionate 440 micrograms twice daily for 12 weeks. Adrenal function was significantly suppressed by fluticasone propionate but not by ciclesonide. Oral candidiasis was reported in 2.4% of patients on ciclesonide versus 22% of patients on fluticasone propionate. Even high daily doses of ciclesonide up to 1280 micrograms did not suppress adrenal function, as measured by 24-hour urinary cortisol excretion (41). This is in accordance with other studies in asthmatic subjects, in which serum or 24-hour urinary cortisol concentrations were unchanged by ciclesonide (42-48). 

A 32-month-old girl developed hypoglycemic seizures (61). She had been given fluticasone propionate 440-880 micrograms/day and up to 5 months before the incident oral glucocorticoids. 

There were no differences in relative fracture risks with different drugs, for example fluticasone, budesonide, beclomethasone (109). In an earlier retrospective study, there was a dose-dependent increase in bone fracture risk with oral glucocorticoids (110). 

Vargas R, Dockhorn RJ, Findlay SR, Korenblat PE, Field EA, Krai KM. Effect of fluticasone propionate aqueous nasal spray versus oral prednisone on the hypothalamic-pituitary-adrenal axis. J Allergy Chn Immunol 1998 102(2) 191-7. 

Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, Kohno S. Oral candidiasis associated with inhaled corticosteroid use comparison of fluticasone and beclomethasone. Ann Allergy Asthma Immunol 2003 90 646-51. 

C. Falcoz, A. Mackie, J. McDowall, J. McRae, L. Yogendran, G. Ventresca, and A. Bye, Oral bioavailability of fluticasone propionate in healthy subjects, Br. J. Clin. Pharmacol. 47 459P (1996). 

Fluticasone propionate (GlaxoSmithKline) is currently the only marketed inhaled corticosteroid with patent protection. It shows very low oral bioavailability, due to a combination of low solubility and oxidative liver metabolism of the C(20) thioester to the corresponding acid which shows much reduced in-vitro activity. 

Oral glucocorticoids such as dexamethasone and prednisolone are still used in patients with severe asthma, though these agents are associated with adverse systemic effects. Inhaled glucocorticoid therapy was introduced in 1972 with beclomethasone dipropionate, which dramatically reduced systemic effects. Fluticasone propionate (launched in 1993) is very efficiently inactivated in the liver, and exhibits low oral bioavailability, which in turn leads to a further reduction in systemic exposure. 

Fluticasone propionate is poorly absorbed from the gastrointestinal tract, and undergoes extensive hepatic first-pass metabolism as a result, the oral bioavailability is reported to be only about 1%. 

Mild persistent or moderate-severe intermittent use an oral or intranasal antihistamine, or an intranasal corticosteroid (e.g. beclometasone or fluticasone). Intranasal decongestants and sodium cromoglicate are useful add-on drugs. 

---