Fluticasone adverse effects

Intranasal corticosteroids are the most effective anti-inflammatory agents used in pediatric patients with allergic rhinitis. Although fewer studies have been conducted in children, results demonstrate that intranasal corticosteroids are effective and well tolerated, with an adverse-effect profile similar to placebo. Mometasone is indicated for children as young as 2 years of age, fluticasone is indicated for children 4 years of age and older, and beclomethasone, budesonide, flunisolide, and triamcinolone are indicated for children 6 years and older.15 Because concerns regarding effect of intranasal steroids on growth exist, the growth of pediatric patients prescribed intranasal steroids should be monitored routinely via stadiometry. 

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). 

Put the following adverse effects of fluticasone aqueous nasal spray in order of occurrence, assigning 1 to the side-effect that occurs most commonly and 3 to the side-effect that occurs least commonly. 

Aerosol treatment is the most effective way to avoid the systemic adverse effects of corticosteroid therapy. The introduction of corticosteroids such as beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, and triamcinolone... 

In a double-bhnd, randomized pilot study of the efficacy and adverse effects of inhaled fluticasone in 25 newborn preterm infants who required mechanical ventilation... 

The effects of inhaled budesonide 800 micrograms/day and fluticasone 400 micrograms/day on bone metabolism, morning cortisol concentrations, and clinical parameters have been studied in eight asthmatic patients (107). There were no changes in serum and bone alkaline phosphatase, osteocalcin, carboxyterminal propeptide of type 1 procollagen, and urinary calcium and deoxypyridinoline concentrations over 6 months. The authors concluded that fluticasone is as effective as twice the dose of budesonide in controlling asthmatic symptoms, without adverse effects on bone metabolism. 

In a double-blind, randomized pilot study of the efficacy and adverse effects of inhaled fluticasone in 25 newborn preterm infants who required mechanical ventilation for treatment of respiratory distress syndrome, the infants were randomized to receive inhaled fluticasone 1000 micrograms/day or placebo (47). The hypothalamic-pituitary-adrenal axis was assessed by the response to corticotropin-releasing factor. AU basal and post-stimulation plasma corticotropin and serum cortisol concentrations were significantly less with inhaled fluticasone than placebo. Cumulative high-dose inhaled glucocorticoids caused moderately severe suppression of both the pituitary and the adrenal glands. This systemic activity is probably associated with pulmonary vascular absorption that avoids hepatic first-pass metabolism. 

There was also an arm treated with inhaled fluticasone alone. Outcome variables were peak flow and asthma symptoms. Both combination and concurrent therapy with fluticasone plus salmeterol resulted in significantly better symptom control and higher peak flows than fluticasone alone. There were no significant differences in the effects of fluticasone plus salmeterol delivered in a combination inhaler versus separate inhalers. Drug-related adverse effects were similar in all three treatment groups most were asthma-related, but hoarseness, dysphonia, and throat irritation were the commonest adverse effects attributed to therapy (1-4%). 

The effects of salmeterol 50 micrograms plus fluticasone 250 micrograms delivered via a combination inhaler and via separate inhalers have been compared in 371 asthmatic patients (18). There were equivalent improvements in peak flows and asthma sjmptoms. Candidiasis, dysphonia, and throat irritation were the commonest adverse effects attributed to treatment and occurred equally in the two groups (35%). Palpitation and tremor, which may have been related to salmeterol, occurred in 2% (for each symptom) of the combination group and in 1% and under 1% of the separate inhaler group. In both of these studies compliance was measured by dose counters on the inhalers and was equivalent in the two groups. 

It appears that treatment with fluticasone plus salmeterol delivered via a combination inhaler is as effective as the same drugs given in separate inhalers and has a similar adverse effects profile. Whether treatment with a combination inhaler improves compliance is not yet proven. 

The risk of new onset diabetes associated with ICS use was evaluated in a pooled data analysis of randomised controlled trials comparing ICS versus open control in patients with asthma (26 trials, total population of 14,993 patients) or COPD (eight trials, total popxilation of 8259) [16 ]. The comparative risk of budesonide compared to fluticasone was also evaluated, in 60 more trials (36,269 patients). The study did not highlight any association of ICS with hyperglycemia or diabetes mellitus (asthma hazards ratio, HR = 0.98,95% Cl = 0.38,2.50. COPD HR = 0.99,95% Cl = 0.67, 1.46). There was no difference in the frequency of these adverse effects between budesonide and fluticasone. 

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. 

In asthmatic human patients, fluticasone propionate improves asthma symptoms and parameters, improves pulmonary function and reduces pulmonary inflammation and airway reactivity (Barnes et al 1998). Regular fluticasone reduces or eliminates the need for rescue 2 agonist therapy and produces progressive improvement in airway reactivity and pulmonary function. In clinical studies, equivalent efficacy is demonstrated with one-quarter of the dose of fluticasone compared with flunisolide and budesonide, and equivalent efficacy is demonstrated with one-half of the dose of fluticasone compared with beclometasone. Adrenal function is less affected by fluticasone propionate at therapeutic doses than with beclometasone, flunisolide or budesonide. Although all aerosolized corticosteroids are considered safe, fluticasone has the least potential for adverse systemic effects and has the most favorable therapeutic index. 

Two recent cases suggest that tics may be rare adverse side-effect of fluticasone [18 ]. A six year old boy developed tics two months after he was started on fluticasone. Once he was switched to ciclesonide, the motor tics resolved after two more months. Moreover, fluticasone seemed to worsen the tics of a 10 year old boy with asthma and Tourette s syndrome. Again, the symptoms returned to baseline after discontinuation of fluticasone. 

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