fluticasone and apaflurane

In 1999, a robust dose-finding study showed that the chlorofluorocarbon (CFC) -free formulation of beclometasone dipropionate (BDP), QVAR (hydrofluoroalkane-134a BDP), produced equivalent asthma control to CFC-BDP at approximately half the daily dose in adults. Since then, a wealth of clinical and pharmaco-vigilance studies have been undertaken to confirm these results and establish dose-potency ratios with other inhaled corticosteroids (ICS). This review summarises the results of studies performed by the manufacturer that have been published since the last comprehensive review of the efficacy and safety of QVAR in 2000. Long-term comparisons with CFC-BDP have confirmed the durability of the 2:1 daily dosing ratio of CFC-BDP:QVAR in adults. Clinical comparisons with other ICS in both symptomatic and asymptomatic patients have established dose-potency ratios of 2: 1 for budesonide:QVAR and 1:1 for fluticasone:QVAR. Furthermore, QVAR has been associated with benefits on asthma symptomatology and quality of life, compared with other ICS that probably arises from its peripheral deposition in the lung.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Double-Blind Method; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Multicenter Studies as Topic; Peak Expiratory Flow Rate; Randomized Controlled Trials as Topic; Treatment Outcome; Vital Capacity

The pathology of asthma has clarified that the inflammatory process in the pulmonary airways of the asthmatic patients determines asthma symptom activity primarily. Among the anti-inflammatory agents currently available to treat asthma, glucocorticoids are the most effective, and the topically active agents, inhaled corticosteroids (ICS) are the most efficient. In Japan, two ICS are commercially available: beclomethasone dipropionate (BDP) and fluticasone propionate(FP). Both agents have been widely used and their clinical efficacy (BDP vs FP at half the microgram dose of the BDP) are largely comparable. In order to bring asthmatic patients maximal benefits of the ICS, enhancing treatment compliance and giving educations (including how to use the ICS) are mandatory. New ICS, which have better drug delivery and be topically more potent, will be available.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Clinical Trials as Topic; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Patient Education as Topic; Pregnenediones

Topics: Administration, Topical; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chemistry, Pharmaceutical; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated

The deposition of nasal aerosols from both aqueous formulations and propellant-based formulations has only minimally been described in rhinitis patients. This study quantified the regional nasal deposition of QNASL(™) (HFA-beclomethasone, nasal aerosol), Flonase(™) (fluticasone propionate, nasal spray) and Nasonex(™) (mometasone furoate monohydrate, nasal spray).. This study was an open label, crossover study in nine patients with allergic rhinitis. The regional nasal deposition of the three nasal products was compared and contrasted following delivery of the (99m)Tc-radiolabeled drug product in each product. The gamma images were merged with magnetic resonance images to quantify regional deposition within the patients.. The HFA propellant-based formulation (QNASL) resulted in an increased retention of drug product in the nasal cavity compared with the two aqueous formulations (Flonase and Nasonex). The aqueous based formulations resulted in increased amount of the delivered dose that dripped from the nostril (6/8 patients for each of the aqueous formulations and 0/8 patients for the HFA propellant formulation) following administration. The percentage of delivered dose that deposited in the back of the throats of the patients was increased and variable (0.1% to 17.6% with Flonase and 0.0 to 4.7% for Nasonex) for the aqueous formulations when compared to dose delivered for the HFA propellant formulation (0.0% to 1.7% for QNASL).. The regional deposition of the HFA propellant based formulation resulted in increased retention of drug product in the nasal cavity and decreased deposition in the back of the throat compared to the two aqueous formulations.

Topics: Adult; Aerosol Propellants; Aerosols; Beclomethasone; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cross-Over Studies; Fluticasone; Humans; Hydrocarbons, Fluorinated; Middle Aged; Mometasone Furoate; Nasal Mucosa; Rhinitis, Allergic; Tomography, Emission-Computed, Single-Photon

Inhaled corticosteroids (ICS) and β2-agonists are the primary pharmacotherapies of asthma management. However, suboptimal medication compliance is common in asthmatics and is associated with increased morbidity. We hypothesized that exhaled breath measurements of the aerosol used in the inhaled medications might prove useful as surrogate marker for asthma medication compliance. To explore this, 10 healthy controls were recruited and randomly assigned to ICS (Flovent HFA) or short acting bronchodilators (Proventil HFA). Both inhalers contain HFA-134a as aerosol propellant. Exhaled breath sampling and pulmonary function tests were performed prior to the inhaler medication dispersion, immediately after inhalation, then at 2, 4, 6, 8, 24, and 48 hours postadministration. At baseline, mean (SD) levels of HFA-134a in the breath were 252 (156) pptv. Immediately after inhalation, HFA-134a breath levels increased to 300 × 10(6) pptv and were still well above ambient levels 24 hours postadministration. The calculated ratio of forced expiratory volume in 1 second over forced vital capacity did not change over time following inhaler administration. This study demonstrates, for the first time, that breath HFA-134a levels can be used to assess inhaler medication compliance. It may also be used to evaluate how effectively the medicine is delivered.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aerosol Propellants; Aerosols; Albuterol; Breath Tests; Bronchodilator Agents; California; Chemistry, Pharmaceutical; Drug Monitoring; Exhalation; Female; Fluticasone; Forced Expiratory Volume; Healthy Volunteers; Humans; Hydrocarbons, Fluorinated; Male; Maximal Midexpiratory Flow Rate; Medication Adherence; Middle Aged; Predictive Value of Tests; Vital Capacity

Current asthma guidelines emphasize domains of impairment and risk for assessing severity and control, noting the need to consider separately the effects of asthma on asthma quality of life and functional capacity. Proper treatment to control asthma should result in improvements in patient well-being and functional status.. To assess asthma-related quality of life after treatment with combination fluticasone propionate and salmeterol delivered via hydrofluoroalkane 134a metered-dose inhaler compared with the individual components alone.. Asthma-related quality of life was assessed as part of two 12-week, randomized, double-blind, placebo-controlled clinical trials comparing the fluticasone propionate-salmeterol combination administered via a single metered-dose inhaler with salmeterol, fluticasone propionate, and placebo administered via traditional chlorofluorocarbon metered-dose inhaler. The Asthma Quality of Life Questionnaire was completed at baseline and end point. Score changes, overall and for the 4 separate domains, were compared within and among the treatment groups.. A total of 720 of 725 patients completed a baseline Asthma Quality of Life Questionnaire and were included in the analyses. In both studies, all mean scores improved significantly from baseline with the fluticasone propionate-salmeterol combination, with significantly greater improvement in the overall score compared with salmeterol alone, fluticasone propionate alone, and placebo groups. Improvements with the combination were also clinically meaningful compared with changes with salmeterol and placebo in both studies and with fluticasone propionate in study 1.. Treatment with combination fluticasone propionate and salmeterol delivered via hydrofluoroalkane metered-dose inhaler resulted in significantly greater improvements in asthma-related quality of life compared with individual components and placebo administered via traditional chlorofluorocarbon metered-dose inhaler.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Quality of Life; Salmeterol Xinafoate; Surveys and Questionnaires; Treatment Outcome; United States

The recently released handheld In-Check device can be used to measure the peak inspiratory flow rate (PIF) of patients and is reportedly useful in determining whether the PIF is sufficient for using inhaler devices. In this study, we evaluated the effects of instructions for the use of the device and of the device type based on measurements of the PIF in asthma.. One hundred and thirty-five asthmatic patients who used a fluticasone propionate Diskus (FP-DK) or a budesonide Turbuhaler (BUD-TH) were studied.. The PIF was measured by the In-Check device. For patients without a sufficient PIF of 50 l/min, instructions for the use of the device were given, and the device was changed to hydrofluoroalkan-beclomethasone dipropionate (HFA-BDP).. A significant correlation between the PIF and peak expiratory flow rate (p < 0.0001) was found. In 10 patients in whom the PIF did not increase to >50 l/min after instructions, the device was changed to HFA-BDP, which resulted in significant improvements in lung function in terms of the forced expiratory volume in 1 s (p = 0.018), peak expiratory flow (p = 0.038) and the maximum expiratory flow rates at 50% (p = 0.018) and 25% (p = 0.011).. Measurement of the PIF by the In-Check device is useful in the clinical management of asthma, to provide an appropriate device so as to improve lung function.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Female; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Inhalation; Male; Middle Aged; Respiratory Function Tests

Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma.. To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC).. In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period.. Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment.. The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Biomarkers; Breath Tests; Child; Cross-Over Studies; Dinoprost; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrogen Peroxide; Inflammation; Interleukins; Male; Nitrates; Nitric Oxide; Nitrites; Prospective Studies; Treatment Outcome; Vital Capacity

The systemic exposure of fluticasone propionate with hydrofluoroalkane propellant compared with chlorofluoro-carbon propellant and the effect of fluticasone propionate hydrofluoroalkane on 24-hour urinary cortisol in children aged 4 to 11 years with asthma were evaluated. Study 1 was an open-label, 2-way crossover study in which 16 subjects were randomized to 7.5 days each of fluticasone propionate hydrofluoroalkane 88 mug twice a day or fluticasone propionate chlorofluorocarbon 88 mug twice a day. In study 2, 63 subjects received 13.5 days of placebo followed by 27.5 days of fluticasone propionate hydrofluoroalkane 88 mug twice a day. The main outcome measure for study 1 was the difference between fluticasone propionate hydrofluoroalkane and fluticasone propionate chlorofluorocarbon in fluticasone propionate AUC(last) (area under the plasma fluticasone propionate concentration-time curve from zero up to the last quantifiable plasma concentration), and for study 2, 24-hour overnight urinary cortisol excretion. In study 1, fluticasone propionate systemic exposure was significantly lower (55%) with hydrofluoroalkane metered dose inhaler compared with chlorofluorocarbon metered dose inhaler. Study 2 showed no statistically significant changes in 24-hour overnight urinary cortisol excretion and no relationship to fluticasone propionate systemic exposure at this dose. The results of these 2 studies showed that in children aged 4 to 11 years with asthma, fluticasone propionate hydrofluoroalkane has lower systemic exposure compared with chlorofluorocarbon and no hypothalamic-pituitary-adrenal axis effects as measured by 24-hour urinary cortisol excretion.

Topics: Administration, Inhalation; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Area Under Curve; Asthma; Child; Child, Preschool; Chlorofluorocarbons; Cough; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fever; Fluticasone; Half-Life; Headache; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Metered Dose Inhalers; Nausea; Respiratory Tract Infections

It is important to evaluate the effects of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP), which shows predominant deposition in the lower airways, on asthmatic inflammation in the lower airways and the Quality of Life (QOL) of asthma patients, as compared with those of fluticasone propionate (FP) Diskus.. Seventy-seven adult patients with mild persistent or more severe asthma who were being treated with FP for >/=3 months were randomly assigned to the HFA-BDP group and continued FP group. The differential count of eosinophils in the peripheral blood, the serum cortisol levels, and pulmonary function parameters were measured before the study and at 3 months after the start of the study treatment. The improvements in the Asthma Quality of Life Questionnaire (AQLQ) scores were also compared. Sputum samples collected by the induced expectoration method (inhalation of 10% saline for 15 min) were divided into the early-phase sputum samples obtained within 15 minutes of the inhalation and the late-phase sputum samples obtained later than 15 minutes after the inhalation, and the eosinophil count and eosinophil cationic protein (ECP) levels were measured.. In the HFA-BDP group (N=40), the differential count of eosinophils in the peripheral blood was significantly decreased as compared with that in the FP group (p=0.009), and the scores in all the domains of the AQLQ and the percentage improvement of the total score were significantly better as compared with those in FP group (p=0.033). The eosinophil count in the late-phase sputum samples (p=0.022) as well as the ECP level in the sputum samples showed more pronounced decreases in the HFA-BDP group as compared with those in the FP group. On the other hand, no significant changes were detected in the pulmonary function values.. Use of the HFA-BDP preparation can more effectively suppress residual inflammation in the lower airways and significantly improve the QOL as compared with use of the FP preparation of asthma patients. Examination of induced sputum samples allows detection of changes in the peripheral airways that cannot be detected by pulmonary function testing.

Topics: Administration, Inhalation; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Middle Aged; Quality of Life

Inhaled corticosteroids (ICSs) delivered by metered-dose inhalers that contain chlorofluorocarbon propellants are being discontinued because of the harmful effects of chlorofluorocarbon on the ozone layer. Therefore, some metered-dose inhaler products are being reformulated with "ozone-friendly" hydrofluoroalkane propellants.. To evaluate treatment with fluticasone propionate hydrofluoroalkane inhalation aerosol, 88, 220, and 440 microg twice daily, vs placebo in patients with asthma receiving an ICS.. Randomized, double-blind, parallel-group, 12-week study.. Mean morning predose percent predicted forced expiratory volume in 1 second increased by 2.2%, 3.2%, and 4.6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, compared with an 8.3% decrease for placebo (P < .001 vs placebo for all groups). Secondary pulmonary function end points and asthma symptoms showed similar improvements compared with placebo. Discontinuation from the study due to lack of efficacy was 50% in the placebo group and 11%, 10%, and 6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively. At week 12, the probability of remaining in the study was 0.89, 0.90, and 0.94 for the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, vs 0.45 for the placebo group (P < .001 for all). Changes in 24-hour urinary cortisol excretion rates were similar among treatment groups.. Fluticasone propionate hydrofluoroalkane, previously shown to be a clinically suitable alternative to fluticasone propionate chlorofluorocarbon, was effective and well tolerated. The ability to switch from fluticasone propionate chlorofluorocarbon and other chlorofluorocarbon-containing ICSs to fluticasone propionate hydrofluoroalkane without sacrificing asthma control or tolerability will facilitate a smooth transition to this nonchlorofluorocarbon-containing medicinal.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Metered Dose Inhalers; Middle Aged; Peak Expiratory Flow Rate

This study compared the efficacy and tolerability of the combination of fluticasone propionate (FP) and salmeterol (SAL) delivered via a single hydrofluoroalkane (HFA) 134a metered-dose inhaler (MDI) with those of its 2 components alone delivered via a chlorofluorocarbon (CFC) MDI and placebo (PLA) delivered via HFA MDI in adolescent and adult patients with persistent asthma that was not controlled by medium doses (equivalent to FP 440-660 microg/d) of inhaled corticosteroids (ICSs).. This was a randomized, double-blind,placebo-controlled, parallel-group study consisting of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period. Participants had to be > or =12 years of age and have a diagnosis of asthma requiring pharmacotherapy for at least 6 months before the study. Patients had to have used ICS therapy for > or =3 months before the study and at a consistent dose for the previous month. Lack of asthma control was defined as a forced expiratory volume in 1 second (FEV(1)) that was 40% to 85% of the predicted value. Patients could not enter the double-blind treatment period if they had 3 days when they required >12 puffs of rescue albuterol per day or >3 nighttime awakenings due to asthma that required treatment with albuterol during the 7 days before the randomization visit. Patients were randomized to receive one of the following treatments delivered via MDI twice daily for 12 weeks: FSC 220/42 microg HFA (2 inhalations of FSC 110/21 microg; 125 microg/21 microg ex-valve); FP 220 microg CFC (2 inhalations of FP 110 microg); SAL 42 microg CFC (2 inhalations of 21 microg); or 2 inhalations of PLA HFA. The primary efficacy end point for FSC versus FP was the mean area under the 12-hour serial FEV(1) curve relative to the prerandomization baseline (FEV(1) AUC(bl)). The primary efficacy end points for FSC versus SAL were the mean change from baseline in morning predose FEV(1) at end point and the probability of not being withdrawn from the study due to worsening asthma. Tolerability assessments included electrocardiograms, routine clinical laboratory tests, vital signs, oropharyngeal examinations, and physical examinations. Adverse events were assessed at each clinic visit.. Thirty-two adolescent and 333 adult patients were randomly assigned to receive double-blind treatment. The treatment groups were comparable at baseline with respect to demographic characteristics (mean age, 38-41 years; white race, 78%-88%) and pulmonary function (mean percent predicted FEV(1), 68%-69%; mean asthma symptom score, 1.6 [scale 0-5]; and mean daily albuterol use, 3.1 puffs). After 12 weeks of treatment, the mean FEV(1) AUC(bl) was significantly greater in patients who received FSC compared with those who received FP, SAL, or PLA (7.0, 3.6, 5.3, and 1.4 L-h, respectively; all comparisons, P < or = 0.020). At end point, the mean change from baseline in morning predose FEV(1) for FSC was significantly greater than that for FP, SAL, and PLA (0.41, 0.19, 0.15, and -0.12 L; all comparisons, P < or = 0.001). During 12 weeks of treatment, 7% of patients receiving FSC were withdrawn due to worsening asthma, compared with 24% of patients receiving SAL and 54% of patients receiving PLA (P < 0.001); 11% of patients receiving FP were withdrawn due to worsening asthma. Treatment with FSC resulted in significant improvements in morning and evening peak expiratory flow compared with FP, SAL, and PLA (both, P < 0.001); need for rescue albuterol compared with FP and PLA (P < or =0.005); and asthma symptom scores compared with PLA (P < 0.001). The tolerability of FSC was similar to that of FP or SAL alone. The incidence of possibly drug-related adverse events was generally similar across treatment groups, and the most common (occurring in > or= 2% of patients) were headache (1%-4%), throat irritation (1%-2%), candidiasis of the mouth/throat (0%-2%), unspecified oropharyngeal plaques (0%-2%), and palpitations (0%-2%).. In these adolescent and adult patients whose asthma was not controlled by medium doses of an ICS, FSC delivered via HFA 134a MDI (2 inhalations of 110/21-microg strength administered BID) was more effective in improving lung function than FP or SAL monotherapy or PLA. All treatments were well tolerated.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Salmeterol Xinafoate; Spirometry; Time Factors; Treatment Outcome

In this randomized crossover study, 22 adult patients with moderate-to-severe persistent bronchial asthma were assigned to one of two groups. Patients in group 1 were administered fluticasone dry powder inhaler (DPI) for 8 weeks followed by a 2-week washout period, then hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) for 8 weeks. After a further 2-week washout, they were again administered fluticasone DPI for 8 weeks. Patients in group 2 were assigned HFA-BDP followed by fluticasone PII and finally HFA-BDP over the same time periods. In both groups, no significant difference was observed in use of beta2-agonists and symptom score between the treatment periods; however, markers of pulmonary function were significantly higher when on HFA-BDP versus fluticasone DPI. Significant increases of morning peak expiratory flow (PEF) (p < 0.01), forced expiratory volume in 1 second (FEV1.0) (p < 0.01), V50 (p < 0.05), and V25 (p < 0.01) were observed at 18 weeks in group 1, whereas there were significant decreases of V50 (p < 0.05) at 18 weeks in group 2. No significant difference was noted in circulating eosinophil count and serum ECP between the 2 treatments; however, ECP in induced sputum and nitric oxide in expired gas were significantly lower (p < 0.05 and < 0.01, respectively) when on HFA-BDP versus fluticasone DPI. HFA-BDP might be delivered to small airways more effectively than fluticasone DPI.

Topics: Adrenergic beta-Agonists; Adult; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cross-Over Studies; Drug Combinations; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Medical Records; Metered Dose Inhalers; Middle Aged; Particle Size; Peak Expiratory Flow Rate

Currently, patients have to keep track of doses to determine when to replace their metered-dose inhalers (MDIs). This study evaluated the performance and patient satisfaction of a novel MDI with an integrated dose counter. In an open-label study at 38 outpatient centres, patients > or =12 years old with asthma or chronic obstructive pulmonary disease (COPD) received two actuations of fluticasone propionate/salmeterol 125/25 microg (115/21 microg ex-actuator) hydrofluoroalkane (ADVAIR) HFA) via MDI with counter twice a day until all 120 actuations were completed. Concordance between counter and diary recordings in patients who reported use of > or =90% of labelled actuations (completer population, n = 228) was high (discrepancy rate of 0.94%) and the incidence of device firing without changes in counter readings was low (0.13%). Mean expected actuations based on canister weights (114) were slightly lower than mean counter (121) and diary reported actuations (120). Upon study completion, 95% of patients were satisfied with the dose counter and 92% agreed it would help prevent them from running out of medication. Safety assessments (intent-to-treat population, n = 237) indicated that the drug was well tolerated. This integrated MDI counter may help patients maintain better disease control by enabling them to accurately track their medication supply.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Patient Satisfaction; Powders; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Treatment Outcome

To evaluate the efficacy and tolerability of fluticasone propionate (FP) hydrofluoroalkane (HFA) in children age 1 to < 4 years with asthma.. Children were assigned (2:1) to receive FP HFA 88 mug (n = 239) or placebo HFA (n = 120) twice daily through a metered-dose inhaler with a valved holding chamber and attached facemask for 12 weeks. The primary efficacy measure was mean percent change from baseline to endpoint in 24-hour daily (composite of daytime and nighttime) asthma symptom scores.. The FP-treated children had significantly greater (P < or = .05) reductions in 24-hour daily asthma symptom scores (-53.9% vs -44.1%) and nighttime symptom scores over the entire treatment period compared with the placebo group. Daytime asthma symptom scores and albuterol use were slightly more decreased with FP than with placebo; however, the differences were not statistically significant. Increases in the percentage of symptom-free days were comparable. The percentage of patients who experienced at least 1 adverse event was similar in the 2 groups. Baseline median urinary cortisol excretion values were comparable between the groups, and there was little change from baseline at endpoint. FP plasma concentrations demonstrated that systemic exposure was low.. FP HFA 88 mug twice daily was effective and well tolerated in pre-school-age children with asthma.

Topics: Administration, Inhalation; Aerosol Propellants; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child, Preschool; Circadian Rhythm; Double-Blind Method; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Infant; Male; Metered Dose Inhalers; Treatment Outcome

To determine whether an antistatic valved holding chamber/mask improves lung bioavailability of hydrofluoroalkane (HFA) fluticasone in young children.. Twelve patients, age 1 to 6 years, with well-controlled asthma were treated with an HFA fluticasone metered-dose inhaler (Flovent HFA) twice daily (440 microg/day). The drug was delivered by tidal breathing through conventional (AeroChamber Plus) and antistatic (AeroChamber MAX) valved holding chambers (VHCs) with masks in a randomized, crossover manner, each for 3 to 7 days. When adherence was 100% at home, blood was collected for measurement of steady-state fluticasone plasma concentration (FPC) 1 hour after the last dose was administered in the clinic. FPC indicates systemic exposure directly and airway delivery indirectly. It was measured by liquid chromatography-mass spectrometry. Data were analyzed by regression analysis.. The mean +/- SD FPC was 107 +/- 30 pg/mL after conventional VHC and 186 +/- 134 pg/mL after the antistatic VHC (P = .03). In 5 patients (40%), the antistatic VHC increased FPC by >/= 100%, to potentially excessive levels in 4 of them; it had little effect in 7 patients.. HFA fluticasone was delivered to the airways by both devices even though the patients could not inhale deeply and breath hold. The antistatic VHC variably increased lung bioavailability. To reduce systemic exposure, the dose should be weaned to the minimum required to maintain asthma control.

Topics: Administration, Inhalation; Androstadienes; Biological Availability; Child; Child, Preschool; Cross-Over Studies; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Infant; Lung; Male; Masks; Static Electricity

Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, > or = 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 microg each morning and 110 microg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25-75% of the vital capacity (FEF25-75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25-75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.

Topics: Administration, Inhalation; Adult; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchi; Bronchodilator Agents; Chlorofluorocarbons; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Middle Aged; Pharmaceutical Solutions; Pulmonary Ventilation; Single-Blind Method; Suspensions

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 microg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV1) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 microg bid; 9.8%, 220 microg bid; 11.2%, 440 microg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Androstadienes; Asthma; Bronchodilator Agents; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Metered Dose Inhalers; Middle Aged; Treatment Outcome

Secondary to phasing out chlorofluorocarbons (CFCs), the fluticasone propionate (FP) pressurized metered-dose inhaler has been formulated in a nonozone-depleting propellant, hydrofluoralkane (HFA) 134a.. To demonstrate equivalent efficacy and safety of FP 200 microg daily propelled by HFA 134a to FP 200 microg daily propelled by CFCs 11 and 12 over a four-week treatment period in pediatric asthmatic patients.. The study was multinational, randomized, double blind and of parallel group design. Eligible patients aged 16 years and younger were steroid naive or receiving 500 microg/day or less of beclomethasone dipropionate, budesonide or flunisolide, or 250 microg/day or less of inhaled FP. The primary efficacy variable was mean morning peak expiratory flow with equivalence determined if the 90% CIs for the treatment differences between groups were within +/- 15 L/min.. Three hundred fifteen patients (mean age 9.3 +/- 2.8 years) were randomly assigned; 158 patients received FP HFA 134a and 157 patients received FP CFC. Over the four-week treatment period, mean morning peak expiratory flow increased from baseline in both groups (14 L/min and 17 L/min, respectively), with a mean treatment difference of -2 L/min. Equivalence was demonstrated between the groups (90% CI -6 to +3 L/min; P=0.589). Both formulations were well tolerated with no serious drug-related events.. FP propelled by HFA 134a has equivalent efficacy and comparable safety to FP propelled by CFC propellants at a microgram equivalent dose in pediatric asthmatic patients.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Asthma; Child; Child, Preschool; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluticasone; Follow-Up Studies; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Male; Nebulizers and Vaporizers; Probability; Respiratory Function Tests; Severity of Illness Index; Treatment Outcome

We wanted to evaluate whether treatment with an inhaled corticosteroid and an inhaled long-acting beta2-agonist is more effective than an inhaled corticosteroid alone for patients using as-needed albuterol who are initiating maintenance treatment.. To compare the efficacy and safety of twice-daily fluticasone propionate (FP) 88 microg and salmeterol 42 microg combined in a chlorofluorocarbon (CFC)-free (hydrofluoroalkane 134a) metered-dose inhaler (MDI) with the individual agents alone, each delivered through an MDI containing CFC propellants, in patient with persistent asthma previously uncontrolled with as-needed short-acting beta2-agonists alone.. Patients with asthma (n = 283) were randomized to twice-daily treatment for 12 weeks with FP 88 microg combined with salmeterol 42 microg (FSC) in a CFC-free MDI or the individual components alone from CFC-containing MDIs.. At endpoint, mean change from baseline in morning predose forced expiratory volume in 1 second was significantly (P < or = 0.016) greater with FSC (0.69 L) compared with FP (0.51 L) or salmeterol (0.47 L). Fewer patients treated with FSC withdrew due to worsening asthma (1%) compared with FP (3%) or salmeterol (8%; P = 0.024). FSC significantly increased (P < or = 0.002) morning and evening peak expiratory flow rate at endpoint (66.5 and 51.5 L/min, respectively) compared with FP (43.0 and 29.9 L/min, respectively) and salmeterol (29.2 and 21.6 L/min, respectively). In addition, asthma symptom scores were reduced, and percentages of days with no asthma symptoms increased in all treatment groups.. Treatment with FSC in a CFC-free MDI is more effective than FP or salmeterol alone in asthma patients who are symptomatic taking short-acting beta2-agonists alone.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Child; Drug Therapy, Combination; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Salmeterol Xinafoate; Time Factors; Treatment Outcome

To compare the lung deposition of radiolabeled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) with chlorofluorocarbon fluticasone propionate (CFC-FP) and chlorofluorocarbon beclomethasone (CFC-BDP).. Six-day, open-label, nonrandomized, crossover study.. Clinical research laboratory.. Nine healthy, nonsmoking, adult volunteers.. On each study day, participants inhaled one or two puffs of 99mTc-labeled HFA-BDP, CFC-FP, or CFC-BDP. All products delivered 50 micro g per puff ex-valve. Subjects used a respiratory training and monitoring device to meet predefined, standardized inhalation patterns. Immediately after inhalation of radiolabeled study drug, planar gamma camera images were obtained.. Radiolabeled HFA-BDP had a higher deposition in the lungs (53% ex-actuator) compared with CFC-FP (12 to 13%) and CFC-BDP (4%). Conversely, CFC-FP and CFC-BDP had a much higher distribution to the oropharynx (72 to 78%, and 82%, respectively) than HFA-BDP (29%). HFA-BDP was deposited evenly throughout the lungs, while CFC-FP and CFC-BDP deposition was primarily in the large central and intermediate airways. Andersen particle size sampling gave mass median aerodynamic diameters for HFA-BDP, CFC-FP, and CFC-BDP of 0.9 micro m, 2.0 micro m, and 3.5 micro m, respectively.. Lung deposition was greater with HFA-BDP compared with CFC-FP and CFC-BDP. Deposition values appeared to be related to the particle size distribution of each inhaler, with the smaller particles of HFA-BDP providing the greatest lung deposition and least oropharyngeal deposition.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aerosol Propellants; Aerosols; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Chlorofluorocarbons; Cross-Over Studies; Female; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Lung; Male; Middle Aged; Particle Size; Radionuclide Imaging; Radiopharmaceuticals; Technetium

To compare the therapeutic ratio of chlorofluorocarbon (CFC) and hydrofluoroalkane-134a (HFA) formulations of fluticasone propionate (FP).. We performed a randomized, placebo-controlled, crossover study comparing 6 weeks of treatment with FP using 500 micro g/d and 1,000 microg/d formulations of CFC and HFA. The primary end points were provocative dose of methacholine causing a 20% fall in FEV1 (PD20) and overnight urinary cortisol/creatinine excretion.. Eighteen patients with mild-to-moderate asthma and geometric mean (SEM) PD20 of 82.3 micro g (19.2 micro g) completed the study. All treatments significantly improved PD20 values and morning peak expiratory flow vs placebo, while 1,000 microg/d was significantly better than 500 microg/d for the CFC formulation of FP (CFC-FP) but not the HFA formulation of FP (HFA-FP). Only 1,000 microg/d of CFC-FP caused significant suppression of overnight urinary cortisol/creatinine compared to placebo. There were no differences between formulations at either dose.. The increased airway benefit with CFC-FP > 500 microg/d was offset by greater systemic effects. Although HFA-FP had fewer systemic effects than CFC-FP at 1,000 microg/d, there was no benefit to increasing HFA-FP to > 500 microg/d.

Topics: Administration, Inhalation; Administration, Topical; Adult; Aerosol Propellants; Androstadienes; Anti-Inflammatory Agents; Asthma; Chlorofluorocarbons; Cross-Over Studies; Female; Fluticasone; Glucocorticoids; Humans; Hydrocarbons, Fluorinated; Male; Single-Blind Method

s: To compare the effect of 4 weeks of treatment with fluticasone propionate (FP), 100 micro g bid, delivered either via the Diskhaler (GlaxoSmithKline; Middlesex, UK) or a hydrofluoroalkane (HFA)-134a pressurized metered-dose inhaler (pMDI) on airway responsiveness.. A single-center, randomized, double-blind, double-dummy, placebo-controlled crossover study.. Outpatients.. Patients with mild asthma who had not received corticosteroids for 4 weeks prior to the study.. FP, 100 micro g bid, via the Diskhaler, HFA-134a pMDI, or placebo for periods of 4 weeks.. The primary efficacy variable was the provocative dose of methacholine causing a 20% fall in FEV(1) (PD(20)) at the end of each 4-week treatment period. The FP formulations were defined as equivalent if the treatment difference was within +/- 1 doubling dose of methacholine. Forty-seven patients were included in the per-protocol population. The baseline PD(20) geometric mean was 0.21 mg, which increased to 0.55 mg with FP via the HFA-134a pMDI and to 0.68 mg with FP via the Diskhaler. The treatment difference between adjusted means was - 0.16 doubling doses (95% confidence interval, - 0.62 to 0.31 doubling doses; p = 0.503). Both significantly decreased airway responsiveness compared to placebo (p < 0.001), and also significantly increased lung function with no difference between the two active groups. FP was well tolerated with few adverse events and no effect on serum cortisol levels.. FP delivered via the HFA-134a pMDI is equivalent to FP via the Diskhaler in reducing airway responsiveness.

Topics: Adult; Aerosol Propellants; Airway Resistance; Androstadienes; Bronchial Hyperreactivity; Bronchial Provocation Tests; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Methacholine Chloride; Middle Aged; Nebulizers and Vaporizers; Treatment Outcome

With the transition to hydrofluoroalkane-134a propellants in metered dose inhalers, it is important to consider the efficacy and safety profiles of formulations containing inhaled corticosteroids. We examined the airway and systemic effects of hydrofluoroalkane-134a fluticasone propionate (FLU-HFA) and beclomethasone dipropionate (BEC-HFA) at recommended labelled doses.. Twenty mild to moderate asthmatics were randomised in crossover fashion to receive 6 weeks of 500 micro g/day followed by 1000 micro g/day FLU-HFA and BEC-HFA. Measurements were made at baseline after placebo run in and washout, and after each randomised treatment. The primary airway outcome for benefit was the dose of methacholine provoking a fall in forced expiratory volume in 1 second (FEV(1)) of 20% or more (methacholine PD(20)) and for systemic adverse effects was overnight urinary cortisol/creatinine (OUCC).. For mean responses, both doses of BEC-HFA and FLU-HFA produced significant improvements in PD(20) compared with baseline. The improvement was not significantly greater with 1000 micro g/day FLU-HFA versus BEC-HFA, a 1.69 fold difference (95% CI 0.94 to 3.04). Both doses of BEC-HFA but not FLU-HFA caused significant suppression of OUCC compared with baseline, with significantly (p<0.05) lower values at 1000 micro g/day for BEC-HFA versus FLU-HFA (1.97 fold difference (95% CI 1.28 to 3.02)).. There was no difference in the airway and systemic effects in patients with mild to moderate asthma between FLU-HFA and BEC-HFA at a dose of 500 micro g/day. At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchoconstrictor Agents; Bronchodilator Agents; Creatinine; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Fluticasone; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Methacholine Chloride

The present study demonstrates the equivalent efficacy for BDP 500 microg bid given via MDI with the new HFA-134a propellant (Chiesi Farmaceutici S.p.A., Parma) compared to a conventional CFC propellant (Becotide, Allen & Hanburys, UK). One hundred and sixteen adult patients with stable mild to moderate asthma (FEV1 > or = 60% of predicted normal) entered a 2-week run-in period where they maintained their own inhaled corticosteroids and were then assigned to a 12-week treatment with the test drug in a randomized, multicentre, double-blind, double-dummy, parallel-group design. Ninety-one patients completed the study period. Morning and evening peak expiratory flow rate (PEFR), use of rescue salbutamol, number of daytime and nighttime asthma attacks, number of nighttime awakenings, and clinical symptoms were recorded daily by patients on a diary card. Pulmonary function tests (FEV1, FVC, PEFR, MEF50 and FEF25) were completed at study entry, at the start of treatment and every 2 weeks thereafter. Morning (08.00-10.00 AM) serum cortisol was measured at the start and at the end of treatment. Adverse events were collected for the total study period. Equivalence between groups was demonstrated for the primary end-point morning PEFR, as well as for evening PEFR and FEV1 (the 95% CI of the treatments' difference was within the 5% of the LSM of BDP CFC). The other secondary pulmonary function tests measured at the clinic visit showed a satisfactory asthma control, albeit without statistically significant differences between groups. Decreases in the use of rescue salbutamol and in clinical symptoms were also reported in both groups, with no differences between them. Adverse events were reported in 81.4% of patients in the BDP HFA group and in 82.5% in the CFC group. There were 73 and 59 adverse drug reactions in the two groups, respectively; the difference was mainly due to differences in taste. No drug-related serious adverse events were reported in either group. No difference was seen for morning serum cortisol between baseline and end of treatment, or between groups. In conclusion, the BDP-HFA 134a formulation proved to be statistically equivalent to the standard BDP CFC product over 12 weeks in adult patients with mild to moderate asthma.

Topics: Adult; Aged; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Least-Squares Analysis; Male; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Severity of Illness Index; Treatment Outcome; United Kingdom; Vital Capacity

Options for step-down therapy include use of inhaled corticosteroids alone or in combination with a long-acting beta2-agonist.. We sought to evaluate step-down therapy with a fluticasone propionate-salmeterol (FP-SM) combination administered through a dry powder inhaler (DPI; Advair Diskus) versus a medium dose of hydrofluoroalkane 143a-beclomethasone dipropionate (HFA-BDP) administered through a breath-actuated pressurized metered-dose inhaler (QVAR Autohaler).. Thirty-nine patients with uncontrolled moderate-to-severe asthma were treated with 1000 microg of DPI-administered BDP twice daily (DPI-BDP) for 4 weeks and then randomized to 200 microg of HFA-BDP twice daily (n = 20) or 100 microg of FP and 50 microg of SM twice daily (FM-SM; n = 19) for 8 weeks in a double-blind, double-dummy, parallel-group design. We measured the provocative dose of methacholine producing a 20% fall in FEV1 (methacholine PD20) as the primary outcome, with secondary outcomes being lung function, surrogate inflammatory markers, diary card responses, quality of life, and safety.. There was a 0.9 (95% confidence interval, 0.5-1.2) doubling dose improvement in methacholine PD20 comparing asthma before versus after DPI-BDP. HFA-BDP maintained this improvement, whereas FP-SM produced a further significant improvement, amounting to a 1.1 (95% confidence interval, 0.2-2.1) doubling dose difference at 8 weeks for FP-SM versus HFA-BDP. Effects on FEV1, peak expiratory flow, and quality of life (symptoms and emotions) were similar to those on methacholine PD20, with a significant difference between FP-SM and HFA-BDP. Suppression of plasma and urinary cortisol and serum osteocalcin levels occurred with DPI-BDP, but values returned to baseline levels within 1 month of HFA-BDP or FP-SM administration.. After high-dose inhaled corticosteroid, stepping down with the combination inhaler conferred further improvements in bronchoprotection, bronchodilatation, and clinical control, but not inflammatory markers, compared with that seen with a medium dose of inhaled corticosteroid.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchial Provocation Tests; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Fluticasone; Humans; Hydrocarbons, Fluorinated; Middle Aged; Outcome Assessment, Health Care; Quality of Life; Respiratory Function Tests; Salmeterol Xinafoate

Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers. We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 microg day(-1)) and HFA-FP (1000 microg day(-1)) in moderate to severe asthma. Symptomatic patients on 500-1000 microg day(-1) CFC-BDP (or equivalent) and short-acting beta-agonist, were randomized to HFA-BDP (n = 101) or HFA-FP (n = 97) after 7-14 (+/-2) day run-in. In the intent-to-treat (ITT) population (n = 198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0.05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within +/-25 l min(-1)) in the two groups: 29.59 (5.19) l min(-1) for HFA-BDP vs. 17.3 (5.45) l min(-1) for HFA-FP (90% CI-0.02, 24.91). For the perprotocol population (n = 121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34.84 (7.08) vs. 20.63 (7.32) l min(-1) P<0.01; 90% CI; 2.66, 31.10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, beta-agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0.01), and eosinophil cationic protein value at week 8 (P<0.01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters. In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 microg(-1) was at least as effective and equally well tolerated as 1000 microg day(-1) HFA-FP.

Topics: Adolescent; Adult; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Eosinophils; Equipment Design; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Leukocyte Count; Male; Middle Aged; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Treatment Outcome

Fluticasone propionate pressurized metered dose inhalers (pMDIs) containing the hydrofluoroalkane (HFA) propellant, HFA 134a, are being developed to replace existing chlorofluorocarbon (CFC) pMDIs. This is part of the ongoing worldwide project to limit the damage to the earth's ozone layer. The in vivo performance and dose proportionality of fluticasone propionate HFA 134a pMDIs was examined for fluticasone propionate doses of 400, 1000 and 2000 microg using the 50, 125 and 250 microg strength pMDIs, respectively. The 125 and 250 microg strength HFA 134a pMDIs were compared with corresponding fluticasone propionate CFC pMDIs. Twenty-three healthy subjects participated in this single dose, randomized, five-way, cross-over study. Serial blood samples were collected 24 h post-dose to measure fluticasone propionate plasma concentrations. Twenty-four hour urinary-free cortisol was also measured before and after dosing. A dose-proportional increase in plasma fluticasone propionate concentrations was observed with increasing dose for the HFA 134a pMDIs. This was associated with a dose-related decrease in urinary cortisol excretion. Similar or lower fluticasone propionate systemic exposure was observed with the HFA 134a pMDIs compared to the corresponding CFC inhalers. The differences in systemic exposure observed for the HFA 134a and CFC pMDIs were too small to produce a differential effect on urinary cortisol excretion. Since fluticasone propionate has negligible oral bioavailability, the systemic exposure, which arises only from pulmonary absorption, is a measure of lung deposition. There was a good correlation between the in vitro fine particle mass produced by the different strengths and types of pMDI and the systemic exposure to fluticasone propionate. Therefore, the fluticasone propionate HFA 134a pMDI is an acceptable pharmaceutical alternative to the current CFC pMDI, producing similar lung deposition and no increase in systemic exposure at microgram equivalent doses.

Topics: Adult; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Chlorofluorocarbons; Cross-Over Studies; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male

This multi-national, double-blind, randomized, parallel-group study compared the efficacy and tolerability of fluticasone propionate 500 microg twice daily propelled either by the non-chlorofluorocarbon (CFC) propellant, hydrofluoroalkane (HFA) 134a, or the CFC propellants 11 and 12 used in the established pressurized metered dose inhaler (pMDI). The study period was 12 months and involved 412 subjects with moderate to severe asthma (HFA 134a pMDI: n = 203; CFC pMDI: n = 209). For the first 3 months, subjects kept a daily record card and attended the clinic every 4 weeks. Thereafter, they kept daily diaries for 2 weeks before each clinic assessment, which were performed at the end of 6, 9 and 12 months. Mean morning peak expiratory flow (PEF) increased during the first week in both treatment groups. By the end of week 12 the adjusted mean increase from baseline in morning PEF was 21 and 23 l min(-1) in the HFA 134a and CFC pMDI groups, respectively, and this increase was maintained throughout the 12-month study period. Similar improvements were detected in other diary card parameters and in clinic lung function measurements. The two groups were shown to be clinically equivalent in terms of all efficacy variables and there were no differences in tolerability. There were few reports of low serum cortisol levels during the 12-month study period, and serum cortisol levels were similar at baseline and after 12 weeks and 12 months of treatment in the two groups. In conclusion, the new HFA 134a fluticasone propionate pMDI is as effective and safe as the established CFC fluticasone propionate pMDI when used at a dosage of 1 mg day(-1).

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Therapeutic Equivalency; Treatment Outcome

This study compared the efficacy and safety of the fluticasone propionate 125 microg pressurized metered dose inhaler (pMDI) propelled by either hydrofluoroalkane (HFA) 134a or chlorofluorocarbon (CFC) propellants, in adult patients with asthma. HFA 134a is a non-ozone depleting propellant used as a replacement for the CFC propellants 11 and 12 which are being phased out in accordance with the Montreal Protocol. Three hundred and eighty patients with mild to moderate asthma and 'room for improvement' in their treatment were randomized to receive fluticasone propionate 250 microg twice daily via pMDIs propelled by either CFC propellants 11 and 12 (n = 195) or HFA 134a (n = 185). Fluticasone propionate significantly improved lung function over the 4-week treatment period in both treatment groups. The improvement in mean morning peak expiratory flow (PEF) after 7 days of treatment was approximately 12 l min(-1) in both groups, rising to approximately 22 l min(-1) at the end of the 4-week treatment period. The adjusted mean difference between the two formulations over weeks 1-4 was -1 l min(-1) (90% confidence interval: -7, 5 l min(-1)), confirming their equivalence. Clinical comparability was also demonstrated with respect to secondary efficacy variables, including daily symptom scores, evening PEF and clinic visit expiratory measurements. There were no clinically relevant differences in adverse events or serum cortisol levels between the two groups. The fluticasone propionate 125 microg HFA 134a pMDI is an effective and well tolerated product and is a suitable replacement for the fluticasone propionate 125 microg CFC pMDI at a microgram equivalent dose.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Therapeutic Equivalency; Treatment Outcome

A randomized, double-blind, cross-over study was conducted to assess the efficacy and safety of fluticasone propionate 1 mg twice daily administered via a pressurized metered dose inhaler (pMDI) containing the new non-chlorofluorocarbon (CFC) propellant (HFA 134a), or the established CFC propellants 11 and 12 in patients with severe asthma. The study comprised a 2-week run-in period followed by two 6-week treatment periods, with no washout period in between. One hundred and nineteen symptomatic adult patients with severe asthma, who were receiving inhaled beclomethasone 2-4 mg day(-1) or equivalent, were randomized to treatment. Patients were randomized to one of two sequence groups (sequence 1: HFA 134a pMDI then CFC pMDI or sequence 2: CFC pMDI then HFA 134a pMDI). The sequence groups differed with respect to mean peak expiratory flow (PEF) at baseline; however, the magnitude of the increase in PEF from baseline during treatment was similar in the two sequence groups. Mean PEF at baseline was 334 l min(-1) in sequence group 1 (HFA 134a-->CFC pMDI) and this increased to 357 l min(-1) and 366 l min(-1) during treatment with the HFA 134a and CFC pMDI, respectively. In sequence group 2 (CFC-->HFA 134a pMDI) mean PEF at baseline was 297 l min(-1) and this increased to 336 l min(-1) and 328 l min(-1) during treatment with the HFA 134a and CFC pMDI, respectively. Based on an overall analysis of the two treatment groups at week 6, equivalence was demonstrated; the mean treatment difference (HFA 134a-CFC pMDI) in morning PEF was 0 l min(-1) (90% confidence interval (CI), for difference between groups: -7, 6 l min(-1)). There was a comparable improvement in secondary efficacy variables, including clinic lung function measurements, in the two treatment groups. The incidence and type of most adverse events were similar in the two treatment groups. There was no difference in the adjusted geometric mean morning serum cortisol levels after treatment with the HFA 134a and CFC pMDI. Therefore, the fluticasone propionate HFA 134a pMDI constitutes a suitable replacement for the established CFC pMDI at a microgram equivalent dose.

Topics: Administration, Inhalation; Adolescent; Adult; Aerosol Propellants; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Chlorofluorocarbons; Chronic Disease; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Forced Expiratory Volume; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Male; Middle Aged; Peak Expiratory Flow Rate; Therapeutic Equivalency; Treatment Outcome

The pharmacokinetic profile of a single dose of inhaled fluticasone propionate (FP) administered via a metered-dose inhaler (MDI), containing either a chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant was investigated in healthy volunteers.. Two randomised, double-blind, crossover studies were conducted, each in 12 male volunteers. Both studies compared pharmacokinetic data after a single inhaled dose of FP 1000 microg from a MDI containing either CFC (CFC MDI) or HFA (HFA MDI) with a single intravenous dose of FP 250 microg.. The maximum plasma FP concentrations after inhalation via the 2 types of MDI were almost identical (0.56 and 0.54 microg/L for CFC MDI and HFA MDI, respectively); bioavailability values of inhaled FP from the 2 MDIs were also similar (geometric mean values: 26.4% via the CFC MDI and 28.6% via the HFA MDI). Inhalation of FP via both MDI formulations produced similar reductions in urinary cortisol excretion over 12 and 24 hours postdose.. The bioavailability values of FP after inhalation via a CFC MDI and an HFA MDI are similar. The 2 formulations deliver comparable amounts of FP, and systemic exposures to FP from the 2 devices, measured by urinary cortisol excretion, are not significantly different.

Topics: Administration, Inhalation; Adult; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Chlorofluorocarbons; Cross-Over Studies; Double-Blind Method; Fluticasone; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Infusions, Intravenous; Male; Nebulizers and Vaporizers

The lung bioavailability (as adrenal suppression) of fluticasone propionate was about twofold greater with chlorofluorocarbons than hydrofluoroalkane as propellant. Direct switching between formulations on a microg equivalent may therefore be inadvisable.

Topics: Adult; Aerosol Propellants; Androstadienes; Anti-Asthmatic Agents; Biological Availability; Chlorofluorocarbons; Dose-Response Relationship, Drug; Fluticasone; Humans; Hydrocarbons, Fluorinated; Hydrocortisone; Lung; Single-Blind Method

Inhaled corticosteroids are used to treat pediatric asthma. The shaking of a pressurized metered-dose inhaler (pMDI) is required to ensure consistency of emitted dose. Delays between shaking and actuating the pMDI are frequent during administration of aerosols to children where a valved holding chamber is used.. In a recent clinical trial, we used a monitoring device to record shaking and actuation of the pMDI and the inhalation profiles of children with asthma while they were inhaling fluticasone hydrofluoroalkane from a valved holding chamber onto an external filter. During the procedure, in vitro and transport samples were generated without a delay between shaking and actuating the pMDI. Emitted dose, expressed as percentage of ex-actuator nominal dose, obtained from the second actuation following a recorded shake-actuation interval for subjects and from in vitro/transport samples (no delay) were compared.. The mean emitted dose was 158.6% (95% CI 150.1-167.2%) (subjects) and 106.8% (95% CI 104.7-108.9%) (in vitro + transport) of the ex-actuator nominal dose (. Delays between shaking and actuating a corticosteroid suspension pMDI resulted in an increase in the emitted dose of the second actuation following the delay. This can be a common occurrence when doses are administered by a caregiver to a patient via a holding chamber. This should be addressed by practitioners educating patients and parents on proper inhaler use. (ClinicalTrials.gov registration NCT01714063.).

Topics: Administration, Inhalation; Aerosols; Asthma; Bronchodilator Agents; Child; Child, Preschool; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Pressure; Random Allocation; Time Factors

Characteristics of inhaled corticosteroids (ICSs) differ, but data comparing the real-life effectiveness of various ICSs for asthma are lacking.. We sought to compare real-life asthma outcomes and costs of extrafine hydrofluoroalkane (HFA)-beclomethasone and fluticasone administered through a pressurized metered-dose inhaler.. This retrospective matched cohort study examined database markers of asthma control from a large US longitudinal health care claims database over 1 baseline and 1 outcome year for 10,312 patients with asthma aged 12 to 80 years receiving their first ICS as HFA-beclomethasone or fluticasone and matched on baseline demographic characteristics and asthma severity.. Patients started on HFA-beclomethasone had significantly higher odds (adjusted odds ratio, 1.19; 95% CI; 1.08-1.31) of achieving overall control (risk and impairment), which was defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection and less than 2 puffs per day of short-acting β-agonist; they also experienced a lower rate of respiratory-related hospitalizations or referrals (adjusted rate ratio, 0.82; 95% CI, 0.73-0.93) than patients started on fluticasone. Other database outcome measures were similar in the 2 cohorts. Prescribed HFA-beclomethasone doses were lower (P < .001) than fluticasone doses (median, 320 μg/d [interquartile range, 160-320 μg/d] vs 440 μg/d [interquartile range, 176-440 μg/d]). Adjusted respiratory-related health care costs were significantly lower for HFA-beclomethasone than fluticasone (mean, $1869 [95% CI, $1727-$2032] vs $2259 [95% CI, $2111-$2404]), representing a mean annual savings of $390 (95% CI, $165-$620) per patient prescribed HFA-beclomethasone rather than fluticasone.. Asthma treatment outcomes were similar or better with HFA-beclomethasone prescribed at significantly lower doses and with lower costs than fluticasone.

Topics: Adult; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Cohort Studies; Female; Fluticasone; Health Care Costs; Humans; Hydrocarbons, Fluorinated; Male; Metered Dose Inhalers; Middle Aged; Retrospective Studies

Existing literature has shown that high relative humidity (RH) affects in vitro aerosol drug delivery of nebulizer and pressurized metered dose inhaler (pMDI) formulations. The aim of this study is to investigate in vitro mouth-throat deposition and lung delivery of selected solution and suspension pMDI formulations, under a range of RH, temperature, and flow rate conditions.. The Alberta Idealized Throat was connected to a collection filter and placed in an environmental control chamber. The formulations selected were beclomethasone dipropionate (BDP) in 13% w/w ethanol/1.3% w/w glycerol and HFA-134a propellant solution ("BDP HFA134a"), BDP in 13% w/w ethanol and HFA-227 propellant solution ("BDP HFA227"), and Flixotide Evohaler (fluticasone propionate 250 μg/dose in HFA-134a suspension). Each of these pMDI formulations was dispersed into the mouth-throat and filter assembly in triplicate, according to an experimental matrix consisting of the following conditions: air flow rates of 28.3, 60, and 90 L/min; 0%, 35%, and 80% RH; operating temperatures of 20°C and 40°C.. There was a general increase in mouth-throat deposition and corresponding decrease in filter deposition (representing lung dose fraction), with increasing RH for both BDP HFA134a and Flixotide pMDIs. Increasing temperature from 20°C to 40°C resulted in decreased mouth-throat deposition and increased lung dose fraction for the solution pMDIs, but generally no effect for the suspension pMDI.. Not only is the dose delivery of pMDI formulations affected by environmental conditions (in some cases causing up to 50% reduction in lung delivery), but solution and suspension formulations also behave differently in response to these conditions. These results have implications during dosage form design, testing, and for usage patient use.

Topics: Administration, Inhalation; Aerosol Propellants; Androstadienes; Beclomethasone; Bronchodilator Agents; Chemistry, Pharmaceutical; Drug Delivery Systems; Ethanol; Fluticasone; Glucocorticoids; Glycerol; Humans; Humidity; Hydrocarbons, Fluorinated; Metered Dose Inhalers; Models, Anatomic; Mouth; Pharynx; Rheology; Temperature

The influence of dentures on residual inhaled corticosteroids (ICSs) in the mouths of elderly asthmatic patients and the appropriate time for gargling after inhaling ICSs are unclear.. Twenty elderly patients in whom moderate persistent asthma was stably controlled using fluticasone propionate Diskus (FP, n = 10) or hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP, n = 10) for more than 3 months and who wore dentures daily were switched to the other type of ICS for 4 weeks in a crossover manner. The residual amount of each ICS in their mouths after inhalation was measured along with determination of peak inspiratory flow (PIF) and pharyngeal culture for detecting Candida albicans.. The total amounts of residual ICSs in gargling fluids (μg) with HFA-BDP were significantly greater than those with FP (15.6 ± 14.6 vs. 11.5 ± 13.8, p = 0.028). The residual amounts of HFA-BDP were significantly greater in the patients with complete dentures than in those with partial dentures. The residual amounts of FP were significantly correlated with the PIF values in the FP treatment (p = 0.013) but not in the HFA-BDP treatment (p = 0.202). No residual ICSs remained after the third gargling in either treatment. The occurrence of candidiasis during the HFA-BDP period was significantly higher than that during the FP treatment (p = 0.046).. The dentures of elderly asthmatics affect the oral residues of ICSs and occurrence of candidiasis in HFA-BDP treatment; meanwhile, the PIF values affected these factors in FP treatment. Three times gargling after inhaling ICSs is required.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Candidiasis, Oral; Dentures; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Male; Mouth; Mouthwashes

Inhaled corticosteroid (ICS) has played an important role in the management of asthma. Although several kinds of ICSs are currently available, there is no established strategy for ICS selection.. Using the data from the 2004 questionnaire surveys by the Niigata Asthma Treatment Study Group, we analyzed relationships between each patient and the ICS employed on the basis of patient background, asthma control and treatment, and indicated characteristics of ICS selection by the physician.. Of 2852 cases, 2279 (79.9%) were ICS users, and 1513 (66.4% of ICS users) were classified as being in the fluticasone propionate (FP) group, 438 (19.2%) in the budesonide (BUD) group, and 240 (10.5%) in the hydrofluoroalkane-beclomethasone (HFA-BDP) group, indicating that FP was a standard ICS in this study. The mean age was significantly lower in the BUD group (52.3+/-18.2 years) and was significantly higher in the HFA-BDP group (59.9+/-17.0 years) than that in the FP group (55.8+/-16.6 years). The proportion of female patients was significantly higher not in the HFA-BDP (46.5%) but in the BUD group (59.0%) than in the FP group (51.1%). These results indicated that BUD was frequently prescribed to young female and HFA-BDP was employed in the elderly patients irrespective of gender compared with FP.. Our study indicates that ICS selection is reasonably adapted to each patient's background at least in the surveyed area. We need to elucidate the characteristics of ICS selection further in the future as new ICS and devices are developed.

Topics: Administration, Inhalation; Age Factors; Androstadienes; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Drug Prescriptions; Female; Fluticasone; Humans; Hydrocarbons, Fluorinated; Japan; Male; Middle Aged; Retrospective Studies; Sex Factors; Surveys and Questionnaires; Treatment Outcome

To investigate the aerosolization and behaviour of microparticles of salmeterol xinafoate (SX) and fluticasone propionate (FP) suspended in hydrofluoroalkane (HFA) propellant.. Microcrystals of SX and FP were produced from poly(ethylene glycol) by antisolvent crystallization. The suspension behaviour and aerosolization of the microcrystals when formulated as metered dose inhalers (MDIs) in HFA 134a propellant was compared with that of microparticles produced by micronization (mSX and mFP) using a glass twin stage impinger and by laser light diffraction using a pressurized cell.. FP microparticles underwent non-reversible aggregation in suspension as seen by a doubling in the volume median diameter compared to the raw material. The degree of aggregation of SX particles in suspension was found to decrease as the particle size of the original particles increased. However, because the SX aggregate size was lowest for the particles with the smallest initial size (mSX), the highest fine particle fraction (FPF) of SX was obtained from a suspension of mSX. The FPFs following aerosolization of FP suspensions were similar although the FPF was lowest for particles with the largest original size.. The size of the aggregates in the HFA suspensions was found to correlate directly with the FPFs determined by impaction.

Topics: Administration, Inhalation; Aerosol Propellants; Aerosols; Albuterol; Androstadienes; Bronchodilator Agents; Chemistry, Pharmaceutical; Crystallization; Drug Stability; Fluticasone; Hydrocarbons, Fluorinated; Metered Dose Inhalers; Particle Size; Polyethylene Glycols; Pressure; Reproducibility of Results; Salmeterol Xinafoate; Technology, Pharmaceutical

Topics: Aerosol Propellants; Androstadienes; Anti-Inflammatory Agents; Biological Availability; Chlorofluorocarbons; Drug Delivery Systems; Fluticasone; Humans; Hydrocarbons, Fluorinated; Lung; Therapeutic Equivalency

The nature of the drug-drug aggregation phenomena between salmeterol xinafoate and fluticasone propionate used in a metered-dose inhaler system has been examined. Interactions between the drugs in the solvents 1,1,2-trichlorotrifloroethane (CFC-113) and 1,1,1,2-tetrafluoroethane (HFA-134a) have been characterised using a focused beam reflectance measurement probe by measuring the average floc size of the drug particles individually and in combination as a function of stirrer rate. The floc composition in the CFC-113 system, where the drug particles cream, was determined by high-performance liquid chromatography analysis. The aggregation behaviour of the individual drugs was shown to depend on the physical and chemical properties of both the drug substance and the media. Larger flocs were observed for salmeterol xinafoate compared with fluticasone propionate, while both drugs formed larger aggregates in HFA-134a compared with in CFC-113. The floc composition studies demonstrated that, in the combined formulation in CFC-113, salmeterol xinafoate and fluticasone propionate aggregate together to form hetero-flocs. The interaction between the two drugs was such that they did not separate on creaming, despite having different densities. The average floc size of the combined drug suspension was also found to depend on the dispersion medium.

Topics: Administration, Inhalation; Aerosols; Albuterol; Androstadienes; Anti-Asthmatic Agents; Chemistry, Pharmaceutical; Chlorofluorocarbons, Ethane; Chlorofluorocarbons, Methane; Drug Interactions; Fluticasone; Hydrocarbons, Fluorinated; Salmeterol Xinafoate

Topics: Administration, Inhalation; Aerosol Propellants; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Chlorofluorocarbons; Fluticasone; Humans; Hydrocarbons, Fluorinated; Nebulizers and Vaporizers

The production of ozone-depleting chlorofluorocarbons (CFCs) was discontinued on 1 January 1996 for all uses deemed non-essential under the Montreal Protocol. However, the use of CFCs as propellants in pressurized metered dose inhalers (pMDIs) was classed as essential, providing an exemption from the agreement. Following extensive research, the hydrofluoroalkanes (HFA) 134a and 227 were identified as the only suitable replacements for CFC propellants in pMDIs. The drug delivery of pMDIs formulated with HFA 134a as a propellant and containing either salbutamol (100 microg per actuation) or fluticasone propionate (125 and 250 microg per actuation) have been assessed for dose uniformity and particle size distribution. All of the HFA 134a pMDIs delivered doses throughout the life of the canisters that were reproducible and within specified regulatory requirements. Each of the products provided an emitted dose which was within +/- 25% of the mean value indicating accurate and consistent dosing (93, 112 and 221 microg per metered dose for the salbutamol 100 microg and fluticasone propionate 125 and 250 microg HFA 134a pMDIs, respectively). These findings were unaffected by changing the storage orientation of the pMDI or by using the device in a manner designed to simulate typical patient use. The particle size distributions of HFA 134a pMDI doses did not differ significantly from those of the corresponding CFC pMDIs. As a result of the similar pharmaceutical performance, it is unnecessary to change the label claim dose of active drug when making the transition from a CFC to an HFA 134a pMDI for salbutamol (Ventolin) and fluticasone propionate (Flixotide). A seamless transition to non-CFC pMDIs will help to maintain the confidence of patients and healthcare professionals in asthma therapy.

Topics: Aerosol Propellants; Albuterol; Androstadienes; Anti-Asthmatic Agents; Bronchodilator Agents; Fluticasone; Humans; Hydrocarbons, Fluorinated; Nebulizers and Vaporizers; Particle Size