Safety Of Budesonide Inhalation Suspension Research Articles

Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma

Budesonide inhalation suspension and the leukotriene receptor antagonist montelukast have demonstrated efficacy in children with mild persistent asthma, but comparative long-term studies in young children are needed. To compare the long-term efficacy and safety of budesonide inhalation suspension and montelukast. After a run-in period, children 2 to 8 years old with mild asthma or recurrent wheezing were randomized to once-daily budesonide inhalation suspension 0.5 mg or once-daily oral montelukast 4 or 5 mg for 52 weeks. Subjects were stepped up to twice-daily budesonide inhalation suspension or oral corticosteroids for mild or severe asthma worsening, respectively. The primary outcome was time to first additional medication for asthma worsening at 52 weeks. Secondary variables included times to the first additional asthma medication measured at 12 and 26 weeks; times to the first asthma exacerbation (mild and severe) measured at 12, 26, and 52 weeks; exacerbation rates (mild and severe) over a period of 52 weeks; diary variables (eg, peak expiratory flow [PEF]); patient-reported outcomes; and Global Physician and Caregiver Assessments. No significant between-group differences were observed for time to first additional asthma medication at 52 weeks; however, time to first additional asthma medication was longer (unadjusted P = .050) at 12 weeks and exacerbation rates were lower over a period of 52 weeks (unadjusted P = .034) for budesonide versus montelukast. Time to first severe exacerbation (requiring oral corticosteroids) was similar in both groups, but the percentage of subjects requiring oral corticosteroids over a period of 52 weeks was lower with budesonide (25.5% vs 32.0%). Peak flow and Caregiver and Physician Global Assessments favored budesonide. Both treatments provided acceptable asthma control; however, overall measures favored budesonide inhalation suspension over montelukast. These findings are consistent with studies in older children demonstrating better outcomes with inhaled corticosteroids versus montelukast.

Safety of Budesonide Inhalation Suspension in Infants Aged Six to Twelve Months With Mild to Moderate Persistent Asthma or Recurrent Wheeze

Purpose of the Study. To compare the safety of budesonide inhalation suspension (BIS) with placebo. Study Population. Infants (aged 6–12 months) with mild-to-moderate persistent asthma or recurrent wheeze. Methods. A multicenter, randomized, double-blinded, parallel-group, placebo-controlled study, in which 141 infants received 0.5 mg of BIS (n = 48), 1.0 mg of BIS (n = 44), or placebo (n = 49) once daily for 12 weeks. The primary variable was adrenal function, which was based on cosyntropin-stimulated plasma cortisol levels. Spontaneous adverse events and clinical laboratory findings were monitored. Results. Overall, the types and frequencies of adverse events reported during the study were comparable across treatment groups. The response to cosyntropin stimulation was similar across treatment groups, with no significant difference between BIS treatment and placebo. Conclusions. The safety profile of BIS was similar to that of placebo, with no suppressive effect on adrenal function in patients 6 to 12 months of age with mild-to-moderate persistent asthma or recurrent wheeze. Reviewer Comments. Inhaled corticosteroids remain the preferred choice for the long-term management of persistent asthma in pediatric patients. In addition, because BIS has become available for clinical use, more and more infants and young children with persistent asthma and/or recurrent episodes of wheezing have been managed with this inhaled antiinflammatory medication. In turn, appropriate questions have arisen from caregivers and providers about the overall safety of this therapy in these very young patients. Although the safety and efficacy of nebulized BIS have been confirmed in well-designed investigations in patients 6 months to 8 years of age, controlled clinical studies addressing the safety and efficacy of inhaled corticosteroids exclusively in the infant age range have been lacking. This current investigation provides very useful safety data for BIS in this understudied infant population. The data demonstrate that once-daily administration of BIS, 0.5 or 1.0 mg, was not associated with a decrease in adrenal function, which was based on cosyntropin-stimulated plasma cortisol levels. This information should be very useful to health care providers who prescribe this medication for young infants with mild-to-moderate persistent asthma or recurrent wheeze.

Efficacy and Safety of Budesonide Inhalation Suspension in Pediatric Asthma: Japan, Phase III Clinical Trials

Efficacy and Safety of Budesonide Inhalation Suspension in Pediatric Asthma: Japan, Phase III Clinical Trials

Safety features of budesonide inhalation suspension in the long-term treatment of asthma in young children

Early inhaled corticosteroid treatment improves symptom control and pulmonary function in children with asthma; however, long-term safety data are limited in infants and young children. This study assessed the long-term safety of budesonide inhalation suspension (BIS) in young children with persistent asthma. To continue to provide BIS to children who needed it-prior to US Food and Drug Administration approval-children 8 years of age or younger with mild, moderate, or severe persistent asthma who previously completed a 52-week open-label study of BIS were enrolled in an additional multicenter, open-label study that was to be concluded upon BIS approval. Patients already receiving BIS continued their current regimens. Patients younger than 4 years and those 4 years of age or older not receiving BIS at baseline started with total daily doses of 0.5 and 1.0 mg, respectively. BIS doses were adjusted throughout the study based on individual response. Adverse events and changes in laboratory parameters, vital signs, and physical examination findings were assessed. Of 198 enrolled patients, 152 (76.8%), 68 (34.3%), and 31 (15.7%) completed 1, 2, and 3 years of BIS treatment (mean daily dose 0.62+/-0.32 mg), respectively. One hundred sixty-six (83.8%) patients experienced an adverse event, of which 8.6% were considered by the investigator to be drug related. Adverse events were those typically occurring in a pediatric asthma population, with respiratory infection (49.0%) and sinusitis (25.3%) occurring at the greatest incidence. Only 2 patients withdrew due to adverse events. Mean changes in laboratory test results and physical examination findings were not clinically important throughout the study. Long-term BIS treatment is well tolerated in young children with persistent asthma, with a safety profile similar to that of short-term administration.

Use and safety of budesonide aerosol in infants with asthma

Inhaled corticosteroids have become a standard first-line therapy for mild to severe persistent asthma in children of all ages. Budesonide inhalation suspension is a nebulized steroid approved for children as young as 12 months. In a study by Berger et al. in this issue of The Journal, the safety of budesonide inhalation suspension was studied in infants aged six to twelve months. The safety profile was excellent, and not significantly different to that of placebo, with no evidence of adrenal suppression. Safety of budesonide inhalation suspension in infants aged six to twelve months with mild to moderate persistent asthma or recurrent wheezeThe Journal of PediatricsVol. 146Issue 1PreviewTo compare the safety of budesonide inhalation suspension (BIS) with placebo in infants 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze. Full-Text PDF

Safety of budesonide inhalation suspension in infants aged six to twelve months with mild to moderate persistent asthma or recurrent wheeze

To compare the safety of budesonide inhalation suspension (BIS) with placebo in infants 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze. In this multicenter, randomized, double-blinded, parallel-group, placebo-controlled study, 141 patients received 0.5 mg BIS (n = 48), 1.0 mg BIS (n = 44), or placebo (n = 49) once daily for 12 weeks. The primary variable was adrenal function, based on cosyntropin-stimulated plasma cortisol levels. Spontaneous adverse events and clinical laboratory findings also were monitored. Overall, the types and frequencies of adverse events reported during the study were comparable across treatment groups. The response to cosyntropin stimulation was similar across treatment groups, with no significant difference between BIS treatment and placebo. The safety profile of BIS was similar to that of placebo, with no suppressive effect on adrenal function in patients 6 to 12 months of age with mild to moderate persistent asthma or recurrent wheeze.

Safety of once-daily budesonide inhalation suspension (Pulmicort Respules ®) in infants aged 6 to 12 months

Rationale To examine the safety of budesonide inhalation suspension (BIS) in infants. Methods A 12-week, double-blind, placebo-controlled, parallel-group study was conducted in infants aged 6-12 months with mild to moderate asthma or recurrent wheeze who were randomized to once-daily BIS 0.5 or 1.0 mg, or placebo. Safety was assessed by adverse events (AEs), changes from baseline in vital signs, physical examinations, oropharyngeal and nasal fungal cultures, and laboratory results. Analysis included all patients who received ≥1 dose and had ≥1 observation (n=141). Results The majority of AEs were mild to moderate; 43 (97.7%), 43 (89.6%), and 43 (87.8%) patients receiving BIS 1 mg, 0.5 mg, and placebo had ≥1 AE, respectively. Five patients receiving BIS experienced serious AEs (2 aggravated asthma, 1 pneumonia, 1 respiratory and 1 viral infection) that were considered unrelated to treatment; 2 of these patients discontinued early. One patient receiving BIS 0.5 mg also discontinued prematurely because of a facial/neck rash. No serious AEs were reported for placebo. Changes in vital signs and laboratory results were comparable among groups. Although difficult to assess over a 12-week period, body length increased in all groups, with mean values of 3.1, 3.5, and 3.7 cm in the infants receiving BIS 1.0 mg, BIS 0.5 mg, and placebo, respectively ( P>0.5). No significant differences between groups in baseline-adjusted oropharyngeal or nasal fungal cultures occurred. Conclusions Consistent with long-term safety of BIS in older pediatric patients, once-daily BIS in infants aged 6 to 12 months was well tolerated and comparable with placebo.

Twice-Daily Budesonide Inhalation Suspension in Infants and Children

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.

Once-daily budesonide inhalation suspension in infants and children

Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. 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. 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. 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. Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged < 4 and > or = 4 years of age.

Short-term and long-term safety of budesonide inhalation suspension in infants and young children with persistent asthma

This article reviews the short-term and long-term safety profile of budesonide inhalation suspension (BIS) for nebulization in infants and young children with persistent asthma. Short-term safety (12 weeks) was assessed by pooling the results from the 3 randomized, double-blind, placebo-controlled, multicenter studies (studies A, B, and C) on the efficacy and safety of once- and twice-daily BIS. Long-term safety of BIS and conventional asthma therapy (CAT) was assessed in 52-week extension studies of the 12-week double-blind trials. CAT consisted of any available therapy for asthma; in 2 studies, CAT could have included treatment with inhaled glucocorticosteroids. Safety was assessed by monitoring adverse events (AEs), physical examinations, and basal and ACTH-stimulated plasma cortisol levels (in a subset of subjects). In the 52-week open-label extensions, the effects of BIS on growth velocity and skeletal age also were determined. In the 12-week studies, a total of 1017 subjects was evaluated for safety; totals of 231, 185, 229, 327, and 45 subjects were randomized to receive placebo or BIS at total daily doses of 0.25 mg, 0.5 mg, 1.0 mg, and 2.0 mg, respectively. Subject demographics and baseline asthma characteristics were similar across treatment groups, except that age, weight, height, and duration of asthma appeared higher in the 2.0-mg daily dose group. For BIS groups, mean age was 58.9 months; mean weight was 20.3 kg; mean height was 108.9 cm, and mean duration of asthma was 3.2 years. There were no differences in the incidence, severity, or types of AEs reported among the BIS and placebo groups. There were no significant differences between placebo and BIS treatment groups in basal or ACTH-stimulated cortisol levels, physical examinations, clinical laboratory values, or fungal cultures. A total of 670 subjects completed the 52-week extension studies; 223 subjects received CAT and 447 received BIS. Median total daily doses of BIS ranged from 0.50 mg to 1.0 mg in the 3 studies, and the mean duration of treatment exposure was 304 ± 119 days and 342 ± 83 days in CAT and BIS groups, respectively. During the 52-week treatment period, the incidences of reported AEs were comparable between treatment groups and were mild-to-moderate in intensity; no new AEs occurred during the 52-week studies compared with 12-week studies. No significant differences were observed between BIS and CAT in basal or ACTH-stimulated cortisol levels, physical examinations, clinical laboratory values, or fungal cultures. There was a small but statistically significant reduction in growth velocity (a difference of 0.8 cm) in the BIS-treated group compared with the CAT group in study A. In studies B and C, growth velocity was not different between BIS and CAT groups. In pooled analyses, no statistically significant differences in growth velocity, standard median heights, or skeletal age were observed between BIS and CAT groups. Short-term and long-term treatment with BIS, over a wide range of doses, was well tolerated for the treatment of persistent asthma in infants and young children. (J Allergy Clin Immunol 1999;104:S200-9)

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. (J Allergy Clin Immunol 1998;102:789-96.)