Flonase
Adrenal suppression from high-dose inhaled fluticasone propionate in children with asthma.

Sim D, Griffiths A, Armstrong D, Clarke C, Rodda C, Freezer N.

Dept of Respiratory and Sleep Medicine, Monash Medical Centre, Melbourne, Australia.

This cross-sectional study was designed to examine the prevalence of adrenocortical suppression in children with asthma treated with high-dose inhaled fluticasone propionate (FP). Children and adolescents (n=50) with asthma, treated with inhaled FP at a dose of > or = 1,000 mg a day for > or = 6 months, were enrolled. Early morning serum cortisol was performed. Subjects with a serum cortisol of < 400 nmol x L(-1) had a tetracosactrin stimulation test. Fifty subjects of mean age 13.1 yrs were treated with a mean dose of 924.7 microg x m(-2) x day(-1) FP for a mean duration of 2 yrs. Of the 50 subjects, 36 (72%) had serum cortisol levels of < 400 nmol x L(-1) and underwent tetracosactrin stimulation test. Of these, 6 (17%) demonstrated a less than two-fold increase in serum cortisol from baseline and peak cortisol level of < or = 550 nmol x L(-1) at 30 or 60 min poststimulation. There was a significant negative correlation between the dose of FP x m(-2) and stimulated peak cortisol level. Biochemical evidence of adrenocortical insufficiency was demonstrated in 12% of the subjects, indicating that high-dose fluticasone propionate use may be associated with dose-dependent adrenocortical suppression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12762348&dopt=Abstract fluticasone Flonase



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Performance of a corticosteroid inhaler with a spacer fashioned from a plastic cold-drink bottle: effects of changing bottle volume.

Taylor SA, Asmus MJ, Liang J, Coowanitwong I, Vafadari R, Hochhaus G.

Shands HealthCare, Gainesville, Florida 32610-0486, USA.

Some clinicians advocate using metered-dose inhaler (MDI) spacers prepared from common household bottles. We evaluated the in vitro aerosol characteristics of fluticasone from the MDI alone and through spacers fashioned from 237-, 500-, 1000-, and 1500-mL polyethylene terephlate plastic cold drink bottles using a cascade impactor. Ten 110-microg actuations of fluticasone were sampled into the impactor during each of five runs with each configuration. The primary outcomes were the respirable dose (i.e., quantity aerosol 1.1-4.7 microm in size) and the quantity trapped in the oropharynx. The mean fluticasone respirable dose from the MDI alone (46.2 microg/actuation) was no different (p > 0.05) compared with the same MDI mated to any of the bottle spacers, regardless of volume. The mean quantity of fluticasone trapped in the oropharynx from the MDI alone (39.2 microg/actuation) was greater (p < 0.001) than the same MDI mated with any bottle spacer (range 1.5-3.5 microg/actuation). These data suggest that any of the bottle spacers tested would be an acceptable method to decrease the quantity of fluticasone that would deposit onto the oropharynx and thereby diminish the risk of topical adverse effects. Among the range of volumes tested, there was no relationship between spacer volume and respirable dose of fluticasone.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12807166&dopt=Abstract fluticasone Flonase



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The effect of a steroid "burst" and long-term, inhaled fluticasone propionate on adrenal reserve.

Nguyen KL, Lauver D, Kim I, Aresery M.

The Reading Hospital and Medical Center, West Reading, Pennsylvania, USA.

BACKGROUND: Although widely used, the effects of steroid "bursts" on the hypothalamic-pituitary-adrenal axis, especially with long-term, concomitant topical steroids use, have not been studied. OBJECTIVE: To examine the effect of a prednisone burst, long-term intranasal steroids, and inhaled fluticasone propionate on the suppression and recovery of adrenal function. METHODS: Adult patients taking long-term intranasal steroids, either moderate-dose (440 microg/d) or high-dose (880 microg/d) inhaled fluticasone propionate, underwent a low-dose cosyntropin stimulation test (LDCST) before and 2 days after a prednisone burst. Suppressed adrenal responses were monitored with a weekly LDCST. Persistent abnormal LDCST results were confirmed by 8-hour cosyntropin infusion. Inhaled fluticasone dosages were decreased; adrenal recovery was evaluated by a monthly LDCST. Adverse effects of steroids were monitored by questionnaires. RESULTS: Sixty-three patients participated in the study. Three of 31 patients not taking inhaled steroids and 1 of 13 patients taking moderate-dose fluticasone had abnormal LDCST results on day 2 after the prednisone burst, which normalized by the second week. In the high-dose fluticasone group, 14 of 19 patients had suppressed LDCST responses on day 2 and adrenal function recovered in 10 of 19 patients by the fourth week. These patients complained significantly of decreased libido (P = 0.02), listlessness (P = 0.03), and weight loss (P = 0.05). High-dose fluticasone (r = 0.66, P < 0.001) and duration of use (r = 0.32, P = 0.01) were statistically correlated with adrenal impairment. Of the 4 patients with persistent adrenal impairment, 3 patients successfully reduced dosages of inhaled fluticasone and adrenal function recovered in 2 to 10 months. CONCLUSIONS: Prednisone bursts induce brief adrenal impairment. Intranasal steroids and moderate-dose fluticasone had no effect on adrenal function. High-dose, inhaled fluticasone caused mild-to-significant adrenal suppression and delayed the recovery after a steroid burst. Avoiding or limiting the duration of high-dose inhaled steroids would minimize systemic adverse effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12877447&dopt=Abstract fluticasone Flonase



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Lung Deposition and Systemic Availability of Fluticasone Diskus and Budesonide Turbuhaler in Children.

Agertoft L, Pedersen S.

Department of Paediatrics, Kolding Hospital, DK-6000 Kolding, Denmark. lone_agertoft dadlnet.dk

Pharmacokinetic studies can be used to measure lung dose of inhaled drugs. The aim of this study was to compare the lung deposition of budesonide (BUD) inhaled from Turbuhaler (AstraZeneca, Lund, Sweden) and fluticasone propionate (FP) inhaled from Diskus (GlaxoSmithKline, London, UK) and to assess if the study design used for pharmacokinetic studies can be simplified. Plasma levels of BUD and FP were measured for 21 hours on five separate days in 15 patients aged 8 to 14 years: (1) Intravenous infusion of 200 mug BUD, (2) intravenous infusion of 200 mug fluticasone dipropionate, (3) inhalation of 800 mug BUD via Turbuhaler, (4) inhalation of 750 mug FP via Diskus, and (5) inhalation of BUD and FP on the same day. Charcoal was ingested to eliminate drug uptake from the gastrointestinal tract. The mean lung deposition of drug after Turbuhaler and Diskus inhalation was 30.8 and 8.0% when BUD and fluticasone were administered on separate days and 29.5% (BUD) and 7.6% (fluticasone) when the two drugs were inhaled on the same day. Lung deposition is four times higher in children after inhalation from Turbuhaler than after inhalation from Diskus. Pharmacokinetic studies with BUD and FP can be simplified because the two treatments can be administered on the same day.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12893646&dopt=Abstract fluticasone Flonase



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Outcomes of patients treated with fluticasone propionate or montelukast sodium.

Allen-Ramey FC, Duong PT, Goodman DC, Sajjan SG, Nelsen LM, Markson L.

Department of Epidemiology, Merck and Company, West Point, Pennsylvania, USA. felicia_ramey merck.com

The authors conducted a retrospective database study of patients with asthma (age range, 6-55 yr) who initiated fluticasone propionate or montelukast sodium treatment between an index period of July 1998 and June 1999. All patients were observed for 12 months before and after the index period. Changes in asthma-related hospitalizations, emergency department visits, oral corticosteroid use, and short-acting beta-agonist use were analyzed. The odds of postindex asthma-related events were estimated. In multivariate analysis, use of a short-acting beta agonist (SABA) was significantly associated with fluticasone treatment (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.21-2.26) and preindex use of SABAs (OR, 1.84; 95% CI, 1.34-2.53). In this managed care population, fluticasone and montelukast provided similar effectiveness.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12964550&dopt=Abstract fluticasone Flonase