Mario Cruz-Rivera

Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children

BACKGROUND Inhaled glucocorticosteroids (GCS) are the most effective long-term controller medications for the treatment of persistent asthma. Currently, however, available delivery devices limit their use in young children. A nebulized formulation of budesonide has been developed to address the needs of infants and young children. OBJECTIVE To evaluate the efficacy and safety of once-daily budesonide inhalation suspension in children 6 months to 8 years old with mild persistent asthma not on inhaled GCS. METHODS Three hundred fifty-nine children were randomized to receive once-daily budesonide inhalation suspension (0.25 mg, 0.50 mg, or 1.0 mg) or placebo via a Pari LC-Jet Plus nebulizer for 12 weeks. Efficacy assessments included nighttime/daytime asthma symptoms, pulmonary function (subset of patients), rescue medication use, and treatment discontinuations. Safety was based on adverse events and assessment of HPA-axis function. RESULTS Demographics, baseline characteristics, asthma symptoms, and pulmonary function were similar across treatment groups. Mean nighttime/daytime asthma symptom scores were 1.19 +/- 0.63 and 1.34 +/- 0.53, respectively. Mean duration of asthma was 36.3 months and mean FEV1 was 81.3% of predicted with 27.7% reversibility. Following 12 weeks of treatment, all budesonide inhalation suspension doses produced significant improvements in nighttime/daytime symptoms (P < or = .049) and significant decreases in rescue medication use (P < or = .038) compared with placebo. Significant improvements (P < or = .044) in FEV1 were observed in the 0.5- and 1.0-mg budesonide inhalation suspension groups. There were no differences between doses of budesonide inhalation suspension. Adverse events and basal and ACTH-stimulated cortisol levels were similar among all groups. CONCLUSION Once-daily administration of budesonide inhalation suspension was well tolerated and effective for the treatment of mild persistent asthma in infants and young children not adequately controlled with bronchodilators or non-GCS antiinflammatory treatments.

Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid–dependent, persistent asthma

BACKGROUND Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma; however, many young children are unable to effectively use currently available inhalers. OBJECTIVE We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension (Pulmicort Respules) in inhaled steroid-dependent asthmatic children. METHODS This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study involving 178 children (age range, 4 to 8 years) at 17 centers in the United States. Budesonide inhalation suspension doses of 0.25 mg, 0.50 mg, or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system. Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores, use of rescue medication, pulmonary function tests, and treatment discontinuation because of worsening symptoms. Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients. RESULTS Baseline demographics, symptom scores, and pulmonary function data were similar across treatment groups. All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P </=.026), reducing use of breakthrough medication (P </=.032), and improving morning peak expiratory flow (P </=.030). The number of dropouts because of worsening asthma was also significantly fewer in the budesonide groups (P </=.015). There were no differences between doses of budesonide. Adverse events and basal and adrenocorticotrophic hormone-stimulated cortisol responses were not different between budesonide and placebo groups. CONCLUSION Budesonide inhalation suspension, 0.25 mg, 0.50 mg, and 1.0 mg twice daily, is an effective and safe treatment for young children with inhaled steroid-dependent, persistent asthma.

Compatibility of Budesonide Inhalation Suspension with Four Nebulizing Solutions

BACKGROUND: Nebulizable medications often are mixed to simplify asthma medication regimens. OBJECTIVE: To establish the in vitro chemical compatibility and stability of budesonide inhalation suspension 0.25 mg/2 mL and 0.5 mg/2 mL mixed in Pari LC Plus jet nebulizer cups with 3 mL of levalbuterol hydrochloride 0.63 mg/3 mL and 1.25 mg/3 mL; 0.5 mL of albuterol sulfate 5 mg/mL; 2 mL of cromolyn sodium 20 mg/2 mL; or 2.5 mL of ipratropium bromide 0.2 mg/mL. METHODS: We developed and validated isocratic HPLC methods to permit separation of the admixture components from aliquots taken 0, 5, 15, and 30 minutes after mixing. Admixtures were prepared and analyzed at room temperature. Each assay was conducted 3 times using separate nebulizer cups. All components were quantified by external standards using HPLC-derived peak area. Appearance and pH of the admixtures were recorded. RESULTS: No additional peaks occurred in any HPLC chromatogram for any medication from any admixture. With the exception of ipratropium bromide at 93%, each admixture retained >97% of the initial concentration of each medication in the nebulizer cup. There was no significant change in pH or visual identification of a precipitate in any admixture of active drugs. CONCLUSIONS: These data support the chemical compatibility of budesonide inhalation suspension for up to 30 minutes with other commonly used nebulized medications for controlling pediatric asthma symptoms.

Effects of budesonide inhalation suspension on hypothalamic-pituitary-adrenal-axis function in infants and young children with persistent asthma

BACKGROUND The initial 12-week, double-blind phases of three studies demonstrated that budesonide inhalation suspension (BIS) is effective and well tolerated in infants and young children (6 months to 8 years of age) with persistent asthma. OBJECTIVE Open-label, 52-week extensions to these studies were conducted to evaluate long-term safety of BIS, including effects of treatment with the lowest effective dose of BIS on hypothalamic-pituitary-adrenal (HPA)-axis function, as compared with conventional asthma therapy (CAT). Complete results of the earlier phases of the studies and of long-term safety are reported elsewhere; only results pertaining to HPA-axis function are summarized here. METHODS Patients eligible for the open-label phases of the three trials were randomized to treatment with nebulized BIS (n = 447) or CAT (n = 223). CAT included short-acting oral or inhaled beta2-agonists, methylxanthines, or cromolyn sodium; in two of the studies, CAT could have included other inhaled corticosteroids. HPA-axis function, which had been evaluated during the 12-week double-blind studies, was again evaluated at the beginning and end of the 52-week study period using basal plasma cortisol concentrations and response to stimulation with a 250-microg dose of adrenocorticotropic hormone. RESULTS There was no evidence of altered HPA-axis function attributable to BIS treatment. No clinically or statistically significant differences in basal or adrenocorticotropic hormone-stimulated plasma cortisol concentrations were observed between BIS and CAT in either the 12-week, double-blind or 52-week, open-label phases of the three studies. CONCLUSIONS The results indicate that treatment with BIS does not result in clinically significant suppression of HPA-axis function in infants and young children.

Once-daily budesonide inhalation suspension in infants and children <4 and ≥4 years of age with persistent asthma

BACKGROUND Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. OBJECTIVE To compare the efficacy and safety of once-daily budesonide inhalation suspension in children < 4 years of age and in those > or = 4 years of age with persistent asthma. METHODS A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic-pituitary-adrenal-axis function. RESULTS In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children < 4 years of age at the 0.25-mg dose level. CONCLUSIONS Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged < 4 and > or = 4 years of age.

Safety profile of budesonide inhalation suspension in the pediatric population: worldwide experience

OBJECTIVE To review the worldwide safety data for budesonide inhalation suspension (Pulmicort Respules) to provide a budesonide inhalation suspension pediatric tolerability profile. DATA SOURCES Clinical study data were obtained from AstraZeneca safety databases used by the US Food and Drug Administration to support the approval of budesonide inhalation suspension and from postmarketing surveillance reports (January 1, 1990, through June 30, 2002). STUDY SELECTION Completed parallel-group studies of patients with asthma 18 years and younger. RESULTS Safety data for budesonide inhalation suspension were pooled from 3 US, 12-week, randomized, double-blind, placebo-controlled studies (n = 1,018); data from their open-label extensions (n = 670) were pooled with data from a fourth US open-label study (n = 335). Data for 333 patients 18 years and younger enrolled in 5 non-US studies also were analyzed. No posterior subcapsular cataracts were reported in any study, and the frequencies of oropharyngeal events and infection with budesonide inhalation suspension were comparable with those of reference treatments. No increased risk of varicella or upper respiratory tract infection was apparent, and budesonide inhalation suspension did not cause significant adrenal suppression in studies assessing this variable. There were small differences in short-term growth velocity between children who received budesonide inhalation suspension and those who received reference treatment in 2 of 5 trials that evaluated this variable. No increased risk of adverse events was apparent from postmarketing reports. CONCLUSIONS Short- and long-term treatment with budesonide inhalation suspension, using a wide range of doses, is safe and well tolerated in children with asthma.

Effective once-daily administration of budesonide inhalation suspension by nebulizer with facemasks or mouthpieces for persistent asthma in infants and young children

This study is a retrospective analysis comparing nebulized budesonide inhalation suspension (BIS; Pulmicort Respules™, AstraZeneca, Wilmington, DE) administered once daily by facemask or mouthpiece...

Twice-daily budesonide inhalation suspension in infants and children <4 and ≥4 years of age with persistent asthma

A retrospective analysis, based on a randomized, placebo-controlled, 12-week study in children 6 months to 8 years of age with persistent asthma, was performed to compare the efficacy and safety of budesonide inhalation suspension 0.25 mg and 0.5 mg twice daily vs. placebo in children <4 and ≥4 years of age. Both age groups demonstrated significant (p ≤ 0.050) improvement in nighttime and daytime asthma symptom scores and decreased bronchodilator use compared with placebo. In addition, the safety profile of twice-daily budesonide inhalation suspension was favorable in both age groups.

The Efficacy & Safety of Once Daily Pulmicort Respules|[trade]| (Budesonide Nebulizing Suspension; BNS) and Placebo (PBO) in Infants and Young Children with Persistant Asthma |[dagger]| 1948

Introduction: The current inhalation devices used to deliver inhaled glucocorticosteroids (iGCS) are not optimal for use by infants or young children with asthma. BNS (Pulmicort Respules™) is a nebulizable iGCS for use in this patient population. A randomized, double-blind, PBO-controlled, multicenter, 12-week study assessed the efficacy and safety of once daily (QD) BNS in infants and young children with persistent asthma not well-controlled on non-iGCS therapies.

The Efficacy and Safety of Pulmicort Respules™ (Budesonide Nebulizing Suspension, BNS) and Placebo (PBO) in Young Asthmatic Children Previously Using Inhaled Glucocorticosteroids (iGCS) ♦ 1976

The Efficacy and Safety of Pulmicort Respules™ (Budesonide Nebulizing Suspension, BNS) and Placebo (PBO) in Young Asthmatic Children Previously Using Inhaled Glucocorticosteroids (iGCS) ♦ 1976