Fluticasone dosing

The incidence of h3q)othalamic-pituitary-adrenal axis suppression caused by concomitant administration of itraconazole and inhaled fluticasone was assessed by synacthen tests in 12 patients with cystic fibrosis receiving both medica-hons versus 12 patients on fluticasone alone [2 ]. The concomitant use of the above medications caused moderate to severe axis suppression in 5/12 patients. In contrast, fluticasone alone, only caused mild suppression in 2/12 controls. Neither itraconazole levels nor fluticasone dose appeared to be correlated with the degree of adrenal suppression. 

For all randomized patients in the inhaled steroid subpopulation, percent reductions in fluticasone dose at the end of double-blind treatment (week 32) are summarized in Table 4. For the inhaled randomized patients subpopulation, there was a highly significant reduction in inhaled steroid dose at the end of the treatment phase in E25 patients compared to placebo p = 0.003). Additionally, the median percent reduction was greater for E25 patients compared to placebo patients in both the Q2 week and Q4 week dosing subgroups. The distribution of... 

Table 4 Percent Reduction in Inhaled Steroid (fluticasone) Dose at End of Treatment Phase (visit 15/week 32) Compared to Baseline (visit 3/week 0) (all randomized patients—inhaled)... 

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

Both budesonide and fluticasone are corticosteroids but fluticasone is more potent than budesonide and has a higher first-pass effect, hence more of the drug is metabolised leading to fewer adverse effects. A dose of 100 pg of budesonide is equivalent to 50 pg of fluticasone. Both budesonide and fluticasone are indicated for the prophylaxis of allergic rhinitis (hay fever). 

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. 

Ketoconazole A potent inhibitor of cytochrome P450 3A4 may increase plasma levels of budesonide and fluticasone during concomitant dosing. The clinical significance is unknown. Use caution. 

Use caution when coadministering high and prolonged doses of fluticasone with ketoconazole and other known cytochrome P450 inhibitors. 

Chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis For the twice-daily maintenance treatment of airflow obstruction in patients with COPD associated with chronic bronchitis. Fluticasone propionate/salmeterol 250 meg per 50 meg twice daily is the only approved dosage for the treatment of COPD associated with chronic bronchitis. Fligher doses, including fluticasone propionate/salmeterol 500 meg per 50 meg, are not recommended. 

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

Recommended Starting Doses of Fluticasone Propionate/Salmeterol for Asthma Patients (Age 12) Taking Inhaled Corticosteroids ... 

Current daily dose of inhaled corticosteroid Recommended strength and dosing schedule of fluticasone propionate/salmeterol... 

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... 

Drake AJ, Howells RJ, Shield JPH, PrendiviUe A, Ward PS, Crowne EC. Symptomatic adrenal insufficiency presenting with hypoglycaemia in asthmatic children with asthma receiving high dose inhaled fluticasone propionate. BMJ 2002 324 1081-2. 

CEC-based metered-dose therapeutic aerosols are in the process of being reformulated with HEA-134a. HEA-formulations of salbutamol (= albuterol) and fluticasone propionate have been shown to be as effective and well tolerated as CEC products at equivalent doses. 

A fixed combination of ICS plus long-acting P2-agonist, such as fluticasone/salmeterol or budes-onide/formoterol, is available and may simplify therapy. However, new insights in treating patients with these combinations on an as needed regimen in combination with a daily low dose maintenance therapy, is still debated. 

Treatment with omalizumab, the monoclonal humanized anti-IgE antibody, is reserved for patients with chronic severe asthma inadequately controlled by high-dose inhaled corticosteroid plus long-acting B-agonist combination treatment (eg, fluticasone 500 meg plus salmeterol 50 meg inhaled twice daily). This treatment reduces lymphocytic, eosinophilic bronchial inflammation and effectively reduces the frequency and severity of exacerbations. It is reserved for patients with demonstrated IgE-mediated sensitivity (by positive skin test or radioallergosorbent test [RAST] to common allergens) and an IgE level within a range that can be reduced sufficiently by twice-weekly subcutaneous injections. 

Aerosol 80, 250 mcg/puff in 80, 100, and 120 dose containers Fluticasone (Flovent)... 

Aerosol 44, 110, and 220 mcg/puff in 120 dose container powder, 50, 100, 250 mcg/activation Fluticasone/Salmeterol (Advair Diskus)... 

Todd G, Dunlop K, McNaboe J, Ryan MF, Carson D, Shields MD. Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate. Lancet 1996 348(9019) 27-9. 

In healthy volunteers, high doses of both budesonide and fluticasone were readily absorbed after inhalation from a mete red-dose aerosol (2). Fluticasone is extensively metabolized by the liver, so measurable concentrations of parent drug in the systemic circulation reflect efficient absorption across the lung. Lower doses of these inhaled glucocorticoids also result in some systemic absorption, reflected in effects on the hypothalamic-pituitary-adrenal axis (3). 

The available studies suggest that fluticasone is more effective than beclomethasone, triamcinolone, or budesonide. However, budesonide delivered by Turbuhaler has equivalent efficacy to fluticasone delivered by metered-dose inhaler or Diskhaler, and is more effective than beclomethasone. When comparative safety is considered, budesonide and triamcinolone delivered by metered-dose inhaler have less systemic activity than fluticasone. Beclomethasone and fluticasone delivered by metered-dose inhaler are equivalent. Budesonide delivered by... 

---