Newswise — A 52-week study examined the long-term safety of the maintenance combination asthma therapy, SYMBICORT® (budesonide/formoterol fumarate dehydrate) Inhalation Aerosol, at up to double the approved dosage.1 More than 700 patients ages 12 years and older with moderate to severe persistent asthma, and who had been previously treated with inhaled corticosteroids, participated in the study.1 Safety was evaluated through several assessments, including the incidence of asthma exacerbations and adverse events.1 The study showed that SYMBICORT, a combination of budesonide, an inhaled corticosteroid (ICS), and formoterol, a rapid and long-acting beta2-agonist (LABA), had a safety profile similar to one of its mono-components, budesonide.1,2 Results were published online and will be a part of the September-October issue of Allergy and Asthma Proceedings.
"In this study, no significant or unexpected adverse events were observed when combining formoterol, a long-acting beta2-agonist, with budesonide for up to one year," 1 said study investigator, Bruce Prenner, MD, University of California, San Diego in La Jolla, California. "The safety data obtained during this study are reassuring and in line with NIH guidelines recommending combination therapy, such as SYMBICORT, for patients whose condition requires more than inhaled corticosteroids alone." 1,3
About the Study ResultsThe study demonstrated that the percentage of patients with at least one asthma exacerbation was significantly lower (p=0.006) with four inhalations twice-daily of SYMBICORT 160/4.5 mcg (12.2%) and numerically lower (p=0.117) with two inhalations twice-daily of SYMBICORT 160/4.5 mcg (14.4%) versus four inhalations twice daily of budesonide 160 mcg (21.8%).1 In the U.S., SYMBICORT is not approved for use as four inhalations twice-daily and is only approved for use as two inhalations twice-daily. 2 The proportion of asthma exacerbations per patient-treatment year was significantly lower with both doses of SYMBICORT (0.174, p=0.004, four inhalations; 0.185, p=0.049, two inhalations) compared to budesonide (0.315).1 The number of patients with at least one hospitalization, emergency department or urgent care visit due to an asthma exacerbation was not statistically significantly different between the treatment groups.1 In addition, no clinically meaningful differences in laboratory, electrocardiogram, or Holter monitor (records heart's electrical activity4) variables were observed between groups.1
Results also demonstrated that SYMBICORT was well tolerated for up to 52 weeks.1 The percentages of patients who experienced any adverse events were similar for both dosing arms of SYMBICORT (88.9%, four inhalations; 84.1%, two inhalations) and budesonide (88.7%).1 Adverse events were mainly mild or moderate in intensity.1 The most common drug-related adverse events, as judged by the investigators, (>2% overall) included oral candidiasis (9.7%), tremor (3.2%) and pharyngolaryngeal pain (2.0%).1 Patient discontinuation rates due to drug-related adverse events were low and similar across all treatment groups.1
"The safety profile of SYMBICORT is based on a robust U.S. development program, which evaluated safety in over 6,000 patients treated with SYMBICORT in Phase I, II and III studies," 5 said Christopher O'Brien, MD, PhD, Senior Director, Medical Science, AstraZeneca. "AstraZeneca is committed to the safety of patients, and we continuously monitor the safety profiles of all our medications."
About the Study DesignThe safety profile of SYMBICORT was assessed during a 52-week randomized, double-blind, parallel-group, single-dummy, multicenter Phase III study1 involving 708 patients ages 12 years and older with moderate to severe persistent asthma previously treated with ICS therapy,1 either alone or in combination.1 After a two-week run-in period when all patients were placed on two inhalations twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 micrograms (mcg) and, as needed, albuterol 90 mcg,1 patients were randomized 3:1:1 to receive either four inhalations twice-daily of SYMBICORT pMDI 160/4.5 mcg (N=443), which is twice its highest recommended dose, 2 two inhalations twice-daily of SYMBICORT pMDI 160/4.5 mcg (N=132), or four inhalations twice-daily of budesonide pMDI 160 mcg (N=133).1
The study assessed patients at eight visits over the 52-week period.1 Safety was evaluated based on the incidence of asthma exacerbations, defined as the use of oral or systemic corticosteroids, hospitalization, or an emergency department or urgent care visit due to asthma exacerbations, adverse events, serious adverse events and discontinuations due to adverse events.1 Additional safety assessments included laboratory evaluations, 24-hour urinary cortisol levels, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), and 24-hour Holter monitoring.1 Adverse events were recorded in daily logs reviewed at each study visit.1
About SYMBICORTSYMBICORT is a combination therapy indicated for the long-term maintenance treatment of asthma in patients 12 years of age and older.2 Administered twice daily,2 SYMBICORT is a combination of two proven asthma medications " budesonide, an inhaled corticosteroid (ICS), and formoterol, a rapid and long-acting beta2-agonist (LABA).2 SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of asthma.2
Important Safety InformationLong acting beta2-adrenergic agonists may increase the risk of asthma-related death. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequately controlled on other asthma-controller medications (e.g., low-to-medium dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with two maintenance therapies. Data from a large placebo-controlled U.S. study compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol may apply to formoterol (a long-acting beta2-adrenergic agonist), one of the active ingredients in SYMBICORT.SYMBICORT is not indicated for the relief of acute bronchospasm.
SYMBICORT should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma.
Particular care is needed for patients who are transferred from systemically active corticosteroids. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.
Patients who are receiving SYMBICORT twice daily should not use additional formoterol or other long-acting inhaled beta2-agonists for any reason.
Common adverse events reported in clinical trials, occurring in > 5 percent of patients, regardless of relationship to treatment, including nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, and stomach discomfort.
For full Prescribing Information, please visit www.MySYMBICORT.com
About AstraZenecaAstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. In the United States, AstraZeneca is a $13.35 billion dollar healthcare business with 12,200 employees committed to improving people's lives. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index. For more information visit http://www.astrazeneca-us.com.
References
1. Peters, S.P., Prenner, B.M., Mezzanotte, W.S., Martin, P., O'Brien, C.D. Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients. Allergy and Asthma Proceedings. Published online, Aug. 08, 2008. http://select.ingentaconnect.com/fstemp/d671784efa0d1b8f0469f3b26fd17951.pdf 2. Symbicort Prescribing Information.3. National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. Retrieved on 28 July 2008. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. 4. National Heart, Lung, and Blood Institute. What Are Holter and Event Monitors? Retrieved on 28 July 2008. http://www.nhlbi.nih.gov/health/dci/Diseases/holt/holt_what.html. 5. Data on File, DA-SYM-01.
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