PROGRAM GUIDE ACAAI Annual Meet ing San Antonio November 5 Practice Excel ence -9, 201

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1 Program Guide Practice Excellence Education. Patient Care. Leadership.

2 Net proceeds donated to the ACAAI Foundation BLOOD, SWEAT & TEARS Headlines Featuring Bo Bice ACAAI FUNDRAISING EVENT Eat, drink and dance the night away to Spinning Wheel And When I Die You ve Made Me So Very Happy and more Sunday, Nov. 8 Reception with cocktails and plated dinner Tickets Available at the ACAAI Registration Desk Tickets $250 Tables $2,300 Show only tickets new this year! $55 with cash bar 6:45 pm Reception 7:45 pm Dinner 9:00 pm Doors Open for show only tickets 9:20 pm Auction 9:30 pm Performance Corporate Tables $10,000

3 Welcome American College of Allergy, Asthma & Immunology Practice Excellence Education. Patient Care. Leadership. November 5-9 Henry B. Gonzalez Convention Center San Antonio, Texas Officers and Board of Regents James L. Sublett, MD, FACAAI President Michael B. Foggs, MD, FACAAI Immediate Past President Bryan L. Martin, DO, FACAAI President-Elect Stephen A. Tilles, MD, FACAAI Vice-President Bradley E. Chipps, MD, FACAAI Treasurer Richard W. Weber, MD, FACAAI Past Immediate Past President Gregory W. Bensch, MD, FACAAI Tao T. Le, MD, MHS, FACAAI Maeve E. O Connor, MD, FACAAI Curtis W. Hedberg, MD, FACAAI Rohit K. Katial, MD, FACAAI Christopher C. Randolph, MD, FACAAI Santiago E. Martinez, MD, FACAAI William S. Silvers, MD, FACAAI Cherie Y. Zachary, MD, FACAAI FIT Representatives: Andrew Nickels, MD ( 15), Sarah W. Spriet, DO ( 16) Speaker of the House: Kathleen R. May, MD, FACAAI ( 15) Executive Medical Director: Bobby Q. Lanier, MD, FACAAI Alliance President: Judy Fineman 1

4 ACAAI Premier Partners The American College of Allergy, Asthma and Immunology recognizes the indispensable role their health care companies play in furthering the mission of the College. ACAAI would like to thank the following companies for their generous support of this year s Annual Scientific Meeting. Diamond $500,000 and above Meda Pharmaceuticals Inc. Gold $100,000 $299,999 AstraZeneca Baxalta US, Inc. Genentech Merck Mylan Specialty L.P. Shire Silver $50,000 $99,999 Alcon Boehringer Ingelheim Pharmaceuticals, Inc. Boston Scientific McNeil Consumer Healthcare Sanofi US Other Contributors Aerocrine, Inc. Allergy Partners BR Surgical, LLC GlaxoSmithKline GREER Lincoln Diagnostics, Inc. Nestlé Nutrition Institute Novartis Pharmaceuticals Corporation Salix Pharmaceuticals, wholly-owned subsidiary of Valeant International, Inc. SmartPractice Sunovion Pharmaceuticals Inc. 2

5 SYMBICORT for your asthma patients 12 years of age uncontrolled on an ICS or whose disease severity clearly warrants an ICS/LABA REV THE FEV 1 SYMBICORT offers something extra sustained * control with better breathing starting within 15 minutes each time 1-3 SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms Mean percent change from baseline FEV 1 was measured at day of randomization, weeks 2 and 12 3 FAST CONTROL Majority of FEV 1 improvement at 15 minutes each time in patients taking SYMBICORT 160/4.5 (n=124) 3 SUSTAINED EFFECT Significant lung function improvement with continuous control, as demonstrated over 12-week study 1,3 REASSURING SENSE OF CONTROL * Sustained improvement in lung function was demonstrated in a 12-week efficacy and safety study. In patients taking SYMBICORT 160/4.5 (n=124) in Study 1, 79% of 2-hour postdose FEV 1 improvement occurred at 15 minutes on day of randomization, 89% at week 2, and 90% at end of treatment. See study designs on next page. IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING WARNING: Long-acting beta 2 -adrenergic agonists (LABA), such as formoterol, one of the active ingredients in SYMBICORT, increase the risk of asthma-related death. A placebo-controlled study with another LABA (salmeterol) showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including formoterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients When treating patients with asthma, prescribe SYMBICORT only for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (eg, discontinue SYMBICORT) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use SYMBICORT for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms SYMBICORT should not be initiated in patients during rapidly deteriorating episodes of asthma or COPD Patients who are receiving SYMBICORT should not use additional formoterol or other LABA for any reason Localized infections of the mouth and pharynx with Candida albicans has occurred in patients treated with SYMBICORT. Patients should rinse the mouth after inhalation of SYMBICORT Lower respiratory tract infections, including pneumonia, have been reported following the inhaled administration of corticosteroids Please see additional Important Safety Information and Brief Summary of full Prescribing Information, including Boxed WARNING, on following pages.

6 SYMBICORT for your asthma patients 12 years of age uncontrolled on an ICS or whose disease severity clearly warrants an ICS/LABA Fast control at 15 minutes each time 1,3 EXPRESS SCRIPTS NATIONAL PREFERRED FORMULARY I N F O R B O T H C O P D A N D A A P SYMBICORT IS ON P R I O N P D I R I C A A T E T E D S E P A T I T H M A, T N S 4 Percent of 2-hour improvement in FEV 1 occurring at 15 minutes over the 12-week study 3 SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms *Baseline is defined as the predose FEV 1 value on the day of randomization. Week 12, last observation carried forward. Administered as 2 inhalations twice daily. Study 1: A 12-week efficacy and safety study. A 12-week, double-blind, placebo-controlled study compared SYMBICORT 160/4.5 mcg, budesonide 160 mcg, formoterol 4.5 mcg, the free combination of budesonide 160 mcg plus formoterol 4.5 mcg in separate inhalers, and placebo, each administered as 2 inhalations twice daily. A total of 596 patients (124 randomized to receive SYMBICORT) 12 years of age were evaluated. The study included a 2-week run-in period with budesonide 80 mcg, 2 inhalations twice daily. Most patients had moderate to severe asthma and were using moderate to high doses of inhaled corticosteroids (ICSs) prior to study entry. This study was designed to assess 2 primary endpoints. The first was predose FEV 1 averaged over 12 weeks, and the second was 12-hour average postdose FEV 1 at week 2. COMPARATOR ARMS: Mean improvement in 2-hour postdose FEV 1 (ml/%) over 12 weeks Day of randomization: SYMBICORT 160/4.5 mcg: 420 ml/20.0%, budesonide 160 mcg: 100 ml/4.4%, formoterol 4.5 mcg: 420 ml/19.9%, budesonide 160 mcg + formoterol 4.5 mcg: 410 ml/19.4%, placebo: 90 ml/4.4%. 2 Weeks: SYMBICORT 160/4.5 mcg: 380 ml/18.6%, budesonide 160 mcg: 120 ml/5.6%, formoterol 4.5 mcg: 270 ml/12.8%, budesonide 160 mcg + formoterol 4.5 mcg: 370 ml/18.0%, placebo: 10 ml/1.2%. End of treatment: SYMBICORT 160/4.5 mcg: 420 ml/20.2%, budesonide 160 mcg: 140 ml/6.5%, formoterol 4.5 mcg: 260 ml/12.3%, budesonide 160 mcg + formoterol 4.5 mcg: 410 ml/19.5%, placebo: 10 ml/0.4%. IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING (cont d) Due to possible immunosuppression, potential worsening of infections could occur. A more serious or even fatal course of chickenpox or measles can occur in susceptible patients It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may occur, particularly at higher doses. Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids Caution should be exercised when considering administration of SYMBICORT in patients on long-term ketoconazole and other known potent CYP3A4 inhibitors As with other inhaled medications, paradoxical bronchospasm may occur with SYMBICORT Immediate hypersensitivity reactions may occur, as demonstrated by cases of urticaria, angioedema, rash, and bronchospasm Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. SYMBICORT should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension Long-term use of orally inhaled corticosteroids may result in a decrease in bone mineral density (BMD). Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating SYMBICORT and periodically thereafter Orally inhaled corticosteroids may result in a reduction in growth velocity when administered to pediatric patients Glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids, including budesonide, a component of SYMBICORT. Close monitoring is warranted in patients with a change in vision or history of increased intraocular pressure, glaucoma, or cataracts In rare cases, patients on inhaled corticosteroids may present with systemic eosinophilic conditions SYMBICORT should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines Beta-adrenergic agonist medications may produce hypokalemia and hyperglycemia in some patients

7 Sustained effect. Control over 12 weeks. 1,3 Change in 2-hour postdose FEV 1 over the 12-week study 3 SYMBICORT 160/4.5 significantly improved predose FEV 1 (P<.05 vs budesonide, formoterol, and placebo) averaged over the course of the study, and also improved 12-hour average postdose FEV 1 (P<.001 vs budesonide, formoterol, and placebo at week 2), coprimary endpoints 1 ; 2-hour postdose FEV 1 over 12 weeks was a secondary endpoint 3 *Week 12, last observation carried forward. Baseline is defined as the predose FEV 1 value on day of randomization. Unadjusted P values based on treatment comparison of absolute mean change from baseline for SYMBICORT vs budesonide and placebo. Administered as 2 inhalations twice daily. The most common adverse reactions 3% reported in asthma clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis The most common adverse reactions 3% reported in COPD clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection SYMBICORT should be administered with caution to patients being treated with MAO inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents Beta-blockers may not only block the pulmonary effect of betaagonists, such as formoterol, but may produce severe bronchospasm in patients with asthma ECG changes and/or hypokalemia associated with nonpotassiumsparing diuretics may worsen with concomitant beta-agonists. Use caution with the coadministration of SYMBICORT INDICATIONS SYMBICORT is indicated for the treatment of asthma in patients 12 years and older (also see Boxed WARNING) SYMBICORT 160/4.5 is indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema SYMBICORT is NOT indicated for the relief of acute bronchospasm References: 1. Noonan M, Rosenwasser LJ, Martin P, O Brien CD, O Dowd L. Efficacy and safety of budesonide and formoterol in one pressurised metereddose inhaler in adults and adolescents with moderate to severe asthma: a randomised clinical trial. Drugs. 2006;66(17): SYMBICORT [package insert]. Wilmington, DE: AstraZeneca; Data on File, , AZPLP Express Scripts Preferred Drug List. Please see Brief Summary of full Prescribing Information, including Boxed WARNING, on following pages. SYMBICORT is a registered trademark of the AstraZeneca group of companies. Express Scripts is a registered trademark of the Express Scripts Holding Company AstraZeneca. All rights reserved /15

8 Trim x 10.5 SYMBICORT 80/4.5 (budesonide 80 mcg and formoterol fumarate dihydrate 4.5 mcg) Inhalation Aerosol SYMBICORT 160/4.5 (budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg) Inhalation Aerosol For Oral Inhalation Only Rx only WARNING: ASTHMA RELATED DEATH Long-acting beta 2-adrenergic agonists (LABA), such as formoterol one of the active ingredients in SYMBICORT, increase the risk of asthma-related death. Data from a large placebo-controlled U.S. study that compared the safety of another long-acting beta 2-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 is considered a class effect of the LABA, including formoterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue SYMBICORT) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use SYMBICORT for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids [see WARNINGS AND PRECAUTIONS]. BRIEF SUMMARY Before prescribing, please see full Prescribing Information for SYMBICORT (budesonide/formoterol fumarate dihydrate). INDICATIONS AND USAGE Treatment of Asthma SYMBICORT is indicated for the treatment of asthma in patients 12 years of age and older. Long-acting beta 2 -adrenergic agonists, such as formoterol one of the active ingredients in SYMBICORT, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients [see WARNINGS AND PRECAUTIONS]. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequately controlled on a long-term asthma-control medication such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g. discontinue SYMBICORT) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as inhaled corticosteroid. Do not use SYMBICORT for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids. Important Limitations of Use: SYMBICORT is NOT indicated for the relief of acute bronchospasm. Maintenance Treatment of Chronic Obstructive Pulmonary Disease (COPD) SYMBICORT 160/4.5 is indicated for the twice daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema. SYMBICORT 160/4.5 is the only approved dosage for the treatment of airflow obstruction in COPD. Important Limitations of Use: SYMBICORT is not indicated for the relief of acute bronchospasm. DOSAGE AND ADMINISTRATION SYMBICORTshould be administered twice daily every day by the orally inhaled route only. After inhalation, the patient should rinse the mouth with water without swallowing [see PATIENT COUNSELING INFORMATION in full Prescribing Information (17.4)]. Prime SYMBICORT before using for the first time by releasing two test sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped, prime the inhaler again by shaking well before each spray and releasing two test sprays into the air away from the face. More frequent administration or a higher number of inhalations (more than 2 inhalations twice daily) of the prescribed strength of SYMBICORT is not recommended as some patients are more likely to experience adverse effects with higher doses of formoterol. Patients using SYMBICORT should not use additional long-acting beta 2 -agonists for any reason [see WARNINGS AND PRECAUTIONS]. Asthma If asthma symptoms arise in the period between doses, an inhaled, short-acting beta 2 -agonist should be taken for immediate relief. Adult and Adolescent Patients 12 Years of Age and Older: For patients 12 years of age and older, the dosage is 2 inhalations twice daily (morning and evening, approximately 12 hours apart). The recommended starting dosages for SYMBICORT for patients 12 years of age and older are based upon patients asthma severity. The maximum recommended dosage is SYMBICORT 160/4.5 mcg twice daily. Improvement in asthma control following inhaled administration of SYMBICORT can occur within 15 minutes of beginning treatment, although maximum benefit may not be achieved for 2 weeks or longer after beginning treatment. Individual patients will experience a variable time to onset and degree of symptom relief. For patients who do not respond adequately to the starting dose after 1-2 weeks of therapy with SYMBICORT 80/4.5, replacement with SYMBICORT 160/4.5 may provide additional asthma control. If a previously effective dosage regimen of SYMBICORT fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options, (e.g., replacing the lower strength of SYMBICORT with the higher strength, adding additional inhaled corticosteroid, or initiating oral corticosteroids) should be considered. Chronic Obstructive Pulmonary Disease (COPD) For patients with COPD the recommended dose is SYMBICORT 160/4.5, two inhalations twice daily. If shortness of breath occurs in the period between doses, an inhaled, short-acting beta 2 -agonist should be taken for immediate relief. CONTRAINDICATIONS The use of SYMBICORT is contraindicated in the following conditions: Primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required. Hypersensitivity to any of the ingredients in SYMBICORT. WARNINGS AND PRECAUTIONS Asthma-Related Death Long-acting beta 2 -adrenergic agonists, such as formoterol, one of the active ingredients in SYMBICORT, increase the risk of asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequately controlled on a long-term asthma-control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g. discontinue SYMBICORT) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use SYMBICORT for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids. A 28-week, placebo controlled US study comparing the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol vs 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34). This finding with salmeterol is considered a class effect of the LABA, including formoterol, one of the active ingredients in SYMBICORT. No study adequate to determine whether the rate of asthma-related death is increased with SYMBICORT has been conducted. Clinical studies with formoterol suggested a higher incidence of serious asthma exacerbations in patients who received formoterol than in those who received placebo. The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups. Deterioration of Disease and Acute Episodes SYMBICORT should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD. SYMBICORT has not been studied in patients with acutely deteriorating asthma or COPD. The initiation of SYMBICORT in this setting is not appropriate. Increasing use of inhaled, short-acting beta 2 -agonists is a marker of deteriorating asthma. In this situation, the patient requires immediate re-evaluation with reassessment of the treatment regimen, giving special consideration to the possible need for replacing the current strength of SYMBICORT with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids. Patients should not use more than 2 inhalations twice daily (morning and evening) of SYMBICORT. SYMBICORT should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short-acting beta 2 -agonist, not SYMBICORT, should be used to relieve acute symptoms such as shortness of breath. When prescribing SYMBICORT, the physician must also provide the patient with an inhaled, short-acting beta 2 -agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice-daily (morning and evening) use of SYMBICORT. When beginning treatment with SYMBICORT, patients who have been taking oral or inhaled, short-acting beta 2 -agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs. Excessive Use of SYMBICORT and Use with Other Long-Acting Beta 2-Agonists As with other inhaled drugs containing beta 2 -adrenergic agents, SYMBICORT should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing long-acting beta 2 -agonists, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using SYMBICORT should not use an additional long-acting beta 2 -agonist (e.g., salmeterol, formoterol fumarate, arformoterol tartrate) for any reason, including prevention of exercise-induced bronchospasm (EIB) or the treatment of asthma or COPD. Local Effects In clinical studies, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in patients treated with SYMBICORT. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral antifungal) therapy while treatment with SYMBICORT continues, but at times therapy with SYMBICORT may need to be interrupted. Patients should rinse the mouth after inhalation of SYMBICORT. Pneumonia and Other Lower Respiratory Tract Infections Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap. Lower respiratory tract infections, including pneumonia, have been reported following the inhaled administration of corticosteroids. In a 6 month study of 1,704 patients with COPD, there was a higher incidence of lung infections other than pneumonia (e.g., bronchitis, viral lower respiratory tract infections, etc.) in patients receiving SYMBICORT 160/4.5 (7.6%) than in those receiving SYMBICORT 80/4.5 (3.2%), formoterol 4.5 mcg (4.6%) or placebo (3.3%). Pneumonia did not occur with greater incidence in the SYMBICORT 160/4.5 group (1.1 %) compared with placebo (1.3%). In a 12-month study of 1,964 patients with COPD, there was also a higher incidence of lung infections other than pneumonia in patients receiving SYMBICORT 160/4.5 (8.1%) than in those receiving SYMBICORT 80/4.5 (6.9%), formoterol 4.5 mcg (7.1%) or placebo (6.2%). Similar to the 6 month study, pneumonia did not occur with greater incidence in the SYMBICORT 160/4.5 group (4.0%) compared with placebo (5.0%). Immunosuppression Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known.if exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents may be considered. The immune responsiveness to varicella vaccine was evaluated in pediatric patients with asthma ages 12 months to 8 years with budesonide inhalation suspension. An open-label, nonrandomized clinical study examined the immune responsiveness to varicella vaccine in 243 asthma patients 12 months to 8 years of age who were treated with budesonide inhalation suspension 0.25 mg to 1 mg daily (n=151) or noncorticosteroid asthma therapy (n=92) (i.e., beta 2 -agonists, leukotriene receptor antagonists, cromones). The percentage of patients developing a seroprotective antibody titer of 5.0 (gpelisa value) in response to the vaccination was similar in patients treated with budesonide inhalation suspension (85%), compared to patients treated with noncorticosteroid asthma therapy (90%). No patient treated with budesonide inhalation suspension developed chicken pox as a result of vaccination. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Transferring Patients From Systemic Corticosteroid Therapy Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although SYMBICORT may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies. During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to SYMBICORT. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with SYMBICORT. Lung function (mean forced expiratory volume in 1 second [FEV 1 ] or morning peak expiratory flow [PEF], beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to inhaled corticosteroids or SYMBICORT may unmask conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions). Some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function. Hypercorticism and Adrenal Suppression Budesonide, a component of SYMBICORT, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since budesonide is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of SYMBICORT in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. 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9 Trim x 10.5 Trim x 10.5 a SYMBICORT (budesonide/formoterol SYMBICORT fumarate dihydrate) (budesonide/formoterol Inhalation Aerosol fumarate dihydrate) Inhalation Aerosol 2 2 h srved carefully for any evidence of observed systemic carefully corticosteroid for any effects. evidence Particular of systemic care should corticosteroid be taken effects. in observing Particular patients care should Clinical be taken Trials in observing Experience patientsin Asthma Clinical Trials Experience in Asthma operatively e or during periods of stress postoperatively for evidence or of during inadequate periods adrenal of stress response. for evidence of inadequate adrenal response. Patients 12 years and older Patients 12 years and older possible that systemic corticosteroid It is effects possible such that as systemic hypercorticism corticosteroid and adrenal effects suppression such as hypercorticism (including adrenal and adrenal crisis) suppression The overall (including safety data adrenal in adults crisis) and The adolescents overall safety are based data upon in adults 10 active- and adolescents and placebo-controlled are based upon clinical 10 active- trials in and which placebo-controlled clinical trials in which dappear in a small number of patients, may appear particularly in a small when number budesonide of patients, is administered particularly at higher when than budesonide recommended is administered doses at 3393 higher patients than recommended ages 12 years doses and older 3393 (2052 patients females ages and years males) and older with (2052 asthma females of varying and 1341 severity males) were with treated asthma with of varying severity were treated with e prolonged periods of time. If such over effects prolonged occur, periods the dosage of time. of SYMBICORT If such effects should occur, be the reduced dosage slowly, of SYMBICORT consistent should with SYMBICORT be reduced slowly, 80/4.5 consistent or 160/4.5 with mcg taken SYMBICORT two inhalations 80/4.5 or once 160/4.5 or twice mcg daily taken for two 12 to inhalations 52 weeks. once In these or twice trials, daily the for patients 12 to 52 weeks. In these trials, the patients pted procedures for reducing systemic accepted corticosteroids procedures for and reducing for management systemic of corticosteroids asthma symptoms. and for management of asthma on symptoms. SYMBICORT had a mean age of 38 on years SYMBICORT and were had predominantly a mean age Caucasian of 38 years (82%). and were predominantly Caucasian (82%). g Interactions With Strong Drug Cytochrome Interactions P450 With 3A4 Strong Inhibitors Cytochrome P450 3A4 Inhibitors The incidence of common adverse events The incidence Table 1 of below common is based adverse upon events pooled in Table data from 1 below three is 12-week, based upon double-blind, pooled data from three 12-week, double-blind, ion a should be exercised when considering Caution should the coadministration be exercised when of SYMBICORT considering the with coadministration ketoconazole, and of SYMBICORT other known with placebo-controlled ketoconazole, and clinical other studies knownin which placebo-controlled 401 adult and clinical adolescent studies patients in which ( males adult and and 253 adolescent females) patients age 12 years (148 and males and 253 females) age 12 years and fg CYP3A4 inhibitors (e.g., ritonavir, strong atazanavir, CYP3A4 clarithromycin, inhibitors (e.g., indinavir, ritonavir, itraconazole, atazanavir, clarithromycin, nefazodone, nelfinavir, indinavir, saquinavir, itraconazole, older nefazodone, were treated nelfinavir, with saquinavir, two inhalations older of SYMBICORT were treated 80/4.5 with two or inhalations SYMBICORT of 160/4.5 SYMBICORT twice 80/4.5 daily. The or SYMBICORT 160/4.5 group twice daily. The SYMBICORT group romycin) because adverse effects telithromycin) related to increased because adverse systemic effects exposure related to to budesonide increased may systemic occur exposure [see DRUG to budesonide was composed may of occur mostly [see Caucasian DRUG was (84%) composed patients with of mostly a mean Caucasian age of 38 (84%) years, patients and a with mean a percent mean age predicted of 38 years, FEV 1 at and a mean percent predicted FEV 1 at RACTIONS t and CLINICAL PHARMACOLOGY INTERACTIONS in full and Prescribing CLINICAL Information PHARMACOLOGY (12.3)]. in full Prescribing Information (12.3)]. baseline of 76 and 68 for the 80/4.5 baseline mcg and of 160/ and mcg 68 for treatment the 80/4.5 groups, mcg respectively. and 160/4.5 Control mcg treatment arms for groups, comparison respectively. Control arms for comparison adoxical e Bronchospasm and Paradoxical Upper Airway Bronchospasm Symptoms and Upper Airway Symptoms included two inhalations of budesonide included HFA metered two inhalations dose inhaler of budesonide (MDI) 80 or HFA 160 metered mcg, formoterol dose inhaler dry powder (MDI) 80 inhaler or 160 (DPI) mcg, formoterol dry powder inhaler (DPI), ith other inhaled medications, SYMBICORT As with other can inhaled produce medications, paradoxical SYMBICORT bronchospasm, can produce which may paradoxical be life threatening. bronchospasm, 4.5 which mcg, or may placebo be life (MDI threatening. and DPI) twice 4.5 mcg, daily. or Table placebo 1 includes (MDI and all adverse DPI) twice events daily. that Table occurred 1 includes at an all incidence adverse of events 3% that in occurred at an incidence of 3% in radoxical ) bronchospasm occurs If following paradoxical dosing bronchospasm with SYMBICORT, occurs it following should be dosing treated with immediately SYMBICORT, with it an should inhaled, be treated any one immediately SYMBICORT with group an inhaled, and more any commonly one SYMBICORT than in the group placebo and group more with commonly twice-daily than dosing. the placebo In considering group with these twice-daily data, dosing. In considering these data, t-acting bronchodilator, SYMBICORT short-acting should be bronchodilator, discontinued immediately, SYMBICORT and should alternative be discontinued therapy should immediately, be instituted. and alternative the increased therapy should average be duration instituted. of patient the exposure increased for average SYMBICORT duration patients of should exposure be taken for SYMBICORT into account, patients as incidences should are be taken into account, as incidences are sediate Hypersensitivity Reactions Immediate Hypersensitivity Reactions not adjusted for an imbalance of treatment not adjusted duration. for an imbalance of treatment duration. s ediate hypersensitivity reactions may Immediate occur after hypersensitivity administration reactions of SYMBICORT, may occur as after demonstrated administration by cases of SYMBICORT, of urticaria, as demonstrated Table 1 Adverse by cases reactions of urticaria, occurring Table at an 1 incidence Adverse of reactions 3% and occurring more commonly at an incidence than placebo of 3% in and the more SYMBICORT commonly than placebo in the SYMBICORT, edema, rash, and bronchospasm. angioedema, rash, and bronchospasm. groups: pooled data from three 12-week, groups: double-blind, pooled data placebo-controlled from three 12-week, clinical double-blind, asthma trials placebo-controlled in patients clinical asthma trials in patients ddiovascular and Central Nervous Cardiovascular System and Effects Central Nervous System Effects 12 years and older 12 years and older ssive beta-adrenergic stimulation Excessive has been beta-adrenergic associated with stimulation seizures, angina, has been hypertension associated or with hypotension, seizures, angina, tachycardia hypertension Treatment* or hypotension, tachycardia Treatment* SYMBICORT Budesonide SYMBICORT Formoterol Budesonide Placebo Formoterol Placebo n rates up to 200 beats/min, arrhythmias, with rates nervousness, up to 200 beats/min, headache, arrhythmias, tremor, palpitation, nervousness, nausea, headache, dizziness, tremor, fatigue, palpitation, malaise, nausea, dizziness, fatigue, malaise, Adverse Event 80/4.5 Adverse mcg Event 160/4.5 mcg 80 mcg 80/4.5 mcg 160 mcg 160/4.5 mcg 4.5 mcg80 mcg 160 mcg 4.5 mcg insomnia [see OVERDOSAGE]. Therefore, and insomnia SYMBICORT, [see OVERDOSAGE]. like all products Therefore, containing SYMBICORT, sympathomimetic like all products amines, containing should sympathomimetic amines, should N = 277 N =124 N =121N = 277N = 109N =124N = 237N =121N = 400N = 109 N = 237 N = 400 sed with caution in patients with be cardiovascular used with caution disorders, in patients especially with cardiovascular coronary insufficiency, disorders, cardiac especially arrhythmias, coronary insufficiency, cardiac arrhythmias, % % % % % % % % % % % % ypertension. and hypertension. n Nasopharyngitis 10.5 Nasopharyngitis g oterol, a component of SYMBICORT, Formoterol, can produce a component a clinically of SYMBICORT, significant cardiovascular can produce a effect clinically some significant patients cardiovascular as effect in some patients as Headache Headache nured by pulse rate, blood pressure, measured and/or by symptoms. pulse rate, Although blood pressure, such effects and/or are symptoms. uncommon Although after administration such effects of are uncommon after administration of oterol at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been Upper respiratory l formoterol at recommended doses, if they occur, the drug may need to discontinued. In addition, beta-agonists have been Upper respiratory rted to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment tract infection n reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment tract infection ession. The clinical significance of depression. these findings The is clinical unknown. significance Fatalities of have these been findings reported is unknown. in association Fatalities with have excessive been reported Pharyngolaryngeal in association with painexcessive Pharyngolaryngeal pain f inhaled sympathomimetic drugs. use of inhaled sympathomimetic drugs. Sinusitis Sinusitis uction in Bone Mineral Density Influenza n Reduction in Bone Mineral Density Influenza eases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled Back pain c Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled Back pain o costeroids. The clinical significance corticosteroids. of small changes The clinical BMD significance with regard to of long-term small changes consequences in BMD with such regard as fracture to long-term is consequences Nasal congestion such as fracture is Nasal 2.5 congestion own. Patients with major risk factors unknown. for decreased Patients with bone major mineral risk content, factors for such decreased prolonged bone immobilization, mineral content, family such as prolonged Stomach discomfort immobilization, family Stomach 1.1 discomfort ry of osteoporosis, post menopausal history status, of osteoporosis, tobacco use, post advanced menopausal age, poor status, nutrition, tobacco or chronic use, advanced use of drugs age, poor that nutrition, can Vomiting or chronic use of drugs that can Vomiting ce bone mass (e.g., anticonvulsants, reduce oral bone corticosteroids) mass (e.g., should anticonvulsants, be monitored oral and corticosteroids) treated with established should be monitored standards and of treated Oral with Candidiasis established standards of s Oral 1.4 Candidiasis Since patients with COPD often have care. multiple Since patients risk factors with COPD for reduced often have BMD, multiple assessment risk factors of BMD for is reduced recommended BMD, assessment prior of BMD is recommended prior n Average Duration of Average Duration of itiating SYMBICORT and periodically to initiating thereafter. SYMBICORT If significant and reductions periodically in thereafter. BMD are If seen significant and SYMBICORT reductions is in still BMD are Exposure seen and (days) SYMBICORT is still 77.7 Exposure (days) idered medically important for that considered patient s COPD medically therapy, important use of for medication that patient s to treat COPD or prevent therapy, osteoporosis use of medication should to be treat or prevent osteoporosis should be., * All treatments were administered as two inhalations * All treatments twice daily. were administered as two inhalations twice daily. gly considered. strongly considered. e ts of treatment with SYMBICORT Effects 160/4.5, of treatment SYMBICORT with 80/4.5, SYMBICORT formoterol 160/4.5, or SYMBICORT placebo on 80/4.5, BMD was formoterol evaluated 4.5, in or a placebo Long-term BMD safety was - asthma evaluated clinical a trials Long-term in patients safety 12 - years asthma and clinical older trials in patients 12 years and older r et of 326 patients (females and males subset 41 of to patients years of (females age) with and COPD males in the 4112-month to 88 years study. of age) BMD with evaluations COPD in the of the 12-month Long-term study. safety BMD evaluations studies in adolescent of the Long-term and adult safety patients studies 12 years in adolescent of age and and older, adult treated patients for 12 up years to 1 year of age at doses and older, up totreated for up to 1 year at doses up to s nd lumbar spine regions were conducted hip and lumbar at baseline spine and regions 52 weeks were conducted using dual at energy baseline x-ray and absorptiometry 52 weeks using (DEXA) dual energy 1280/36 x-ray mcg/day absorptiometry (640/18 mcg (DEXA) twice 1280/36 daily), revealed mcg/day neither (640/18 clinically mcg twice important daily), changes revealed in neither incidence clinically nor important new types changes of in the incidence nor new types of T s. Mean changes in BMD from baseline scans. to Mean end changes of treatment in BMD were from small baseline (mean to changes end of ranged treatment from were small (mean g/cmchanges 2 ). adverse ranged events from emerging after g/cmlonger periods of treatment. Similarly, no significant or unexpected patterns of abnormalities o ). adverse events emerging after longer periods of treatment. Similarly, no significant unexpected patterns of abnormalities OVA results for total spine and total ANCOVA hip BMD results based for on total the end spine of and treatment total hip time BMD point based showed on the that end all of geometric treatment LS time Mean point were showed observed that all geometric for up to 1 LS year Mean in safety were measures observed for including up to 1 chemistry, year in safety hematology, measures ECG, including Holter monitor, chemistry, and hematology, HPA-axis ECG, Holter monitor, and HPA-axis h s for the pairwise treatment group ratios comparisons for the pairwise were close treatment to 1, indicating group comparisons that overall, were bone close mineral to 1, density indicating for total that hip overall, assessments. bone mineral density for total hip assessments. otal spine regions for the 12 month and time total point spine were regions stable for over the 12 the month entire treatment time point period. were stable over the entire treatment period. Clinical Trials Experience in Chronic Clinical Obstructive Trials Experience Pulmonary in Chronic Disease Obstructive Pulmonary Disease ct on Growth Effect on Growth The incidence of common adverse events The incidence Table of 2 below common is based adverse upon events pooled in Table data 2 from below two is double-blind, based upon placebocontrolled to pediatric clinical patients. studies Monitor (6 and the12 months controlled in clinical duration) studies in which (6 and adult months COPD in patients duration) (496 in which males 771 and adult 275 females) COPD patients (496 males and 275 females) pooled data from two double-blind, placebo-. y inhaled corticosteroids may cause Orally a reduction inhaled corticosteroids in growth velocity may when cause administered a reduction in to growth pediatric velocity patients. when Monitor administered the g th of pediatric patients receiving SYMBICORT growth of pediatric routinely patients (e.g., receiving via stadiometry). SYMBICORT To minimize routinely the (e.g., systemic via stadiometry). effects of orally To minimize 40 years the of systemic age and effects older of were orally treated 40 with years SYMBICORT of age and older 160/4.5, were two treated inhalations with SYMBICORT twice daily. Of 160/4.5, these patients two inhalations 651 were twice daily. Of these patients 651 were e ed corticosteroids, including SYMBICORT, inhaled corticosteroids, titrate each patient s including dose SYMBICORT, to the lowest titrate dosage each that patient s effectively dose controls to the lowest his/herdosage treated that for effectively 6 months controls and 366 his/her were treated treated for for 12 6 months. The and SYMBICORT 366 were treated group for was 12 composed months. The of SYMBICORT mostly Caucasian group (93%) was composed of mostly Caucasian (93%) f toms [see DOSAGE AND ADMINISTRATION symptoms [see and DOSAGE USE IN SPECIFIC AND ADMINISTRATION POPULATIONS]. and USE IN SPECIFIC POPULATIONS]. patients with a mean age of 63 years, patients and a mean with percent a mean predicted age of 63 FEV years, 1 at and baseline a mean of percent 33%. Control predicted arms FEV for 1 comparison at baseline of 33%. Control arms for comparison d ucoma and Cataracts Glaucoma and Cataracts included two inhalations of budesonide included HFA (MDI) two 160 inhalations mcg, formoterol of budesonide (DPI) HFA 4.5 mcg (MDI) or 160 placebo mcg, (MDI formoterol and DPI) (DPI) twice 4.5 daily. mcg or placebo (MDI and DPI) twice daily. s coma, increased intraocular pressure, Glaucoma, and cataracts increased have intraocular been reported pressure, in patients and cataracts with asthma have been and reported COPD following patients Table with 2 asthma includes and all COPD adverse following events that Table occurred 2 includes at an incidence all adverse of events 3% in that the occurred SYMBICORT at an incidence group and of more 3% commonly in the SYMBICORT than group and more commonly than r ong-term administration of inhaled the corticosteroids, long-term administration including of budesonide, inhaled corticosteroids, a component including of SYMBICORT. budesonide, Therefore, a component in the placebo of SYMBICORT. group. In considering Therefore, these in the data, placebo the increased group. In average considering duration these of data, patient the exposure increased to average SYMBICORT duration should of patient be exposure to SYMBICORT should be g monitoring is warranted in patients close with monitoring a change is in warranted vision or with in patients history with of increased a change intraocular vision or pressure, with history glaucoma, of increased taken intraocular into account, pressure, as incidences glaucoma, are not taken adjusted into account, for an imbalance as incidences of treatment are not adjusted duration. for an imbalance of treatment duration. s or cataracts. and/or cataracts. Table 2 Adverse reactions occurring Table at an 2 incidence Adverse of reactions 3% and occurring more commonly at an incidence than placebo of 3% in and the more commonly than placebo in the e ts of treatment with SYMBICORT Effects 160/4.5, of treatment SYMBICORT with 80/4.5, SYMBICORT formoterol 160/4.5, 4.5, SYMBICORT or placebo 80/4.5, on development formoterol of 4.5, or placebo SYMBICORT on development group: pooled of data from SYMBICORT two double-blind, group: placebo-controlled pooled data from two clinical double-blind, COPD trials placebo-controlled clinical COPD trials acts or glaucoma were evaluated cataracts in a subset or of glaucoma 461 patients were with evaluated COPD in a the subset 12-month of 461 study. patients Ophthalmic with COPD examinations the 12-month a Treatment* study. Ophthalmic examinations SYMBICORT Treatment* Budesonide SYMBICORT Formoterol Budesonide Placebo Formoterol Placebo conducted at baseline, 24 weeks, were and 52 conducted weeks. There at baseline, were subjects weeks, and (6%) 52 with weeks. an increase There were in posterior 26 subjects subcapsular (6%) with an increase in posterior subcapsular ) 160/4.5 mcg 160 mcg 160/ mcg mcg 160 mcg 4.5 mcg e from baseline to maximum value score (>0.7) from during baseline the to randomized maximum treatment value (>0.7) period. during Changes the randomized in posterior treatment subcapsular period. Changes in posterior subcapsular. N = 771 N = 275 N = N 771 = 779 N = N 275 = 781 N = 779 N = 781 es of >0.7 from baseline to treatment scores maximum of >0.7 from occurred baseline 11 to patients treatment (9.0%) maximum in the occurred SYMBICORT in /4.5 patients group, (9.0%) in the n Adverse SYMBICORT Event 160/4.5 group, Adverse % Event % % % % % % % tients (3.8%) in the SYMBICORT 480/4.5 patients group, (3.8%) 5 patients in the SYMBICORT (4.2%) in the 80/4.5 formoterol group, group, 5 patients and 6 (4.2%) patients in (5.2%) the formoterol in the group, - Nasopharyngitis and 6 patients (5.2%) in the Nasopharyngitis bo group. placebo group. lt Oral candidiasis Oral 6.0 candidiasis inophilic Conditions and Eosinophilic Churg-Strauss Conditions Syndrome and Churg-Strauss Syndrome Bronchitis Bronchitis re cases, patients on inhaled corticosteroids In rare cases, may patients present on with inhaled systemic corticosteroids eosinophilic may conditions. present with Some systemic of these eosinophilic patients conditions. Some of these patients e Sinusitis Sinusitis clinical features of vasculitis consistent have clinical with Churg-Strauss features of vasculitis syndrome, consistent a condition with Churg-Strauss that is often treated syndrome, with systemic a condition that is often treated with systemic Upper respiratory tract Upper respiratory tract costeroid therapy. These events usually, corticosteroid but not therapy. always, These have been events associated usually, but with not the always, reduction have and/or been withdrawal associated with of the reduction and/or withdrawal of infection viral infection 3.5 viral corticosteroid therapy following the oral introduction corticosteroid of therapy inhaled corticosteroids. following the introduction Physicians of should inhaled be corticosteroids. alert to eosinophilia, Physicians should be alert to eosinophilia, ulitic - rash, worsening pulmonary vasculitic symptoms, rash, cardiac worsening complications, pulmonary and/or symptoms, neuropathy cardiac presenting complications, in their and/or patients. neuropathy Average presenting Duration in of their patients. Average Duration of Exposure (days) Exposure (days) sal relationship between budesonide A causal and relationship these underlying between conditions budesonide has not and been these established. underlying conditions has not been established. - xisting Conditions Coexisting Conditions * All treatments were administered as two inhalations * All treatments twice daily. were administered as two inhalations twice daily. BICORT, like all medications containing SYMBICORT, sympathomimetic like all medications amines, containing should be sympathomimetic used with caution amines, patients should with be used Lung with infections caution other in patients than pneumonia with Lung (mostly infections bronchitis) other than occurred pneumonia in a greater (mostly percentage bronchitis) of occurred subjects in treated a greater with percentage of subjects treated with ulsive t disorders or thyrotoxicosis convulsive and in those disorders who are or unusually thyrotoxicosis responsive and in to those sympathomimetic who are unusually amines. responsive Doses of to the sympathomimetic SYMBICORT 160/4.5 amines. compared Doses of the with placebo SYMBICORT (7.9% 160/4.5 vs. 5.1%, compared respectively). with placebo There were (7.9% no vs. clinically 5.1%, respectively). important or unexpected There were no clinically important or unexpected ed f beta 2 -adrenoceptor agonist albuterol, related beta when 2 -adrenoceptor administered agonist intravenously, albuterol, have when been administered reported to aggravate intravenously, preexisting have been patterns reported of to abnormalities aggravate preexisting observed for patterns up to 1 year of abnormalities in chemistry, observed haematology, for up ECG, to 1 ECG year (Holter) in chemistry, monitoring, haematology, HPA-axis, ECG, bone ECG (Holter) monitoring, HPA-axis, bone rtes mellitus and ketoacidosis. diabetes mellitus and ketoacidosis. mineral density and ophthalmology assessments. mineral density and ophthalmology assessments. T okalemia and Hyperglycemia Hypokalemia and Hyperglycemia Postmarketing Experience Postmarketing Experience -adrenergic l agonist medications may Beta-adrenergic produce significant agonist medications hypokalemia may in some produce patients, significant possibly hypokalemia through intracellular some patients, The following possibly through adverse reactions intracellular have The been following reported adverse during post-approval reactions have use been of reported SYMBICORT. during Because post-approval these reactions use of SYMBICORT. are Because these reactions are y ting, which has the potential to shunting, produce which adverse has cardiovascular the potential effects to produce [see adverse CLINICAL cardiovascular PHARMACOLOGY effects in [see full CLINICAL reported PHARMACOLOGY voluntarily from a in population full reported of uncertain voluntarily size, from it is not a population always possible of uncertain to reliably size, estimate it is not their always frequency possible or to reliably estimate their frequency or cribing Information (12.2)]. The Prescribing decrease in Information serum potassium (12.2)]. is The usually decrease transient, in serum not requiring potassium supplementation. is usually transient, establish not requiring a causal supplementation. relationship to drug establish exposure. a causal Some relationship of these adverse to drug reactions exposure. may Some also have of these been adverse observed reactions in clinical may also have been observed in clinical cally d significant changes in blood Clinically glucose significant and/or serum changes potassium in blood were glucose seen infrequently and/or serum during potassium clinical were studies seen with infrequently studies during with SYMBICORT. clinical studies with studies with SYMBICORT. BICORT r at recommended doses. SYMBICORT at recommended doses. Cardiac disorders: angina pectoris, tachycardia, Cardiac disorders: atrial and angina ventricular pectoris, tachyarrhythmias, tachycardia, atrial atrial and fibrillation, ventricular extrasystoles, tachyarrhythmias, atrial fibrillation, extrasystoles, y ERSE REACTIONS ADVERSE REACTIONS palpitations palpitations -acting beta 2-adrenergic agonists, Long-acting such as formoterol beta 2-adrenergic one of the agonists, active ingredients such as formoterol in SYMBICORT, one of the increase active ingredients the risk Endocrine SYMBICORT, disorders: increase hypercorticism, the risk growth Endocrine velocity disorders: reduction hypercorticism, in pediatric patients growth velocity reduction in pediatric patients othma-related death. Currently available of asthma-related data are inadequate death. Currently to determine available whether data are concurrent inadequate use to of determine inhaled cortico- or other long-term asthma steroids control drugs or other mitigates long-term the asthma increased control risk drugs of asthma-related mitigates the death increased from LABA. risk of asthma-related Gastrointestinal death disorders: from oropharyngeal LABA. Gastrointestinal candidiasis, disorders: nausea oropharyngeal candidiasis, nausea whether Eye concurrent disorders: use cataract, of inhaled glaucoma, cortico- increased Eye disorders: intraocular cataract, pressure glaucoma, increased intraocular pressure sids lable k data from controlled clinical Available trials suggest data from that controlled LABA increase clinical the trials risk suggest of asthma-related that LABA increase hospitalization the risk inof asthma-related Immune system hospitalization disorders: immediate in Immune and delayed system hypersensitivity disorders: immediate reactions, and such delayed as anaphylactic hypersensitivity reaction, reactions, angioedema, such as anaphylactic reaction, angioedema, atric l and adolescent patients. Data pediatric from a and large adolescent placebo-controlled patients. US Data study from that a large compared placebo-controlled the safety of another US study long- beta 2-adrenergic agonist (salmeterol) acting beta or placebo 2-adrenergic added agonist to usual (salmeterol) asthma therapy or placebo showed added an increase to usual in asthma-related therapy showed an increase in asthma-related that compared bronchospasm, the safety urticaria, of another exanthema, long- bronchospasm, dermatitis, pruritus urticaria, exanthema, dermatitis, pruritus sg Metabolic and nutrition disorders: hyperglycemia, Metabolic and hypokalemia nutrition disorders: hyperglycemia, hypokalemia s in patients receiving salmeterol deaths [see WARNINGS in patients receiving AND PRECAUTIONS]. salmeterol [see WARNINGS AND PRECAUTIONS]. Musculoskeletal, connective tissue, and bone disorders: muscle cramps emic s Musculoskeletal, connective tissue, and bone disorders: muscle cramps and inhaled corticosteroid use Systemic may result and inhaled the following: corticosteroid use may result in the following: Candida c albicans infection [see WARNINGS - Candida AND albicans PRECAUTIONS] infection [see WARNINGS AND PRECAUTIONS] Nervous system disorders: tremor, dizziness Nervous system disorders: tremor, dizziness Pneumonia r or lower respiratory tract - infections Pneumonia in patients or lower with respiratory COPD [see tract WARNINGS infections in AND patients PRECAUTIONS] with COPD [see WARNINGS Psychiatric AND PRECAUTIONS] disorders: behavior disturbances, Psychiatric sleep disorders: disturbances, behavior nervousness, disturbances, agitation, sleep disturbances, depression, restlessness nervousness, agitation, depression, restlessness Immunosuppression [see WARNINGS - Immunosuppression AND PRECAUTIONS] [see WARNINGS AND PRECAUTIONS] Hypercorticism and adrenal suppression - Hypercorticism [see WARNINGS and AND adrenal PRECAUTIONS] suppression [see WARNINGS AND PRECAUTIONS] ngrowth effects in pediatric patients -[see Growth WARNINGS effects AND in pediatric PRECAUTIONS] patients [see WARNINGS AND PRECAUTIONS] Respiratory, thoracic, and mediastinal Respiratory, disorders: dysphonia, thoracic, and cough, mediastinal throat irritation disorders: dysphonia, cough, throat irritation Skin and subcutaneous tissue disorders: Skin skin and bruising subcutaneous tissue disorders: skin bruising Vascular disorders: hypotension, hypertension Vascular disorders: hypotension, hypertension Glaucoma e and cataracts [see WARNINGS - Glaucoma AND PRECAUTIONS] and cataracts [see WARNINGS AND PRECAUTIONS] DRUG INTERACTIONS DRUG INTERACTIONS yuse clinical trials are conducted Because under widely clinical varying trials conditions, are conducted adverse under reaction widely rates varying observed conditions, in the adverse clinical reaction trials rates In clinical observed studies, in the concurrent clinical trials administration In clinical of SYMBICORT studies, concurrent and other administration drugs, such of as SYMBICORT short-acting and betaother 2 -agonists, drugs, intranasal such as short-acting beta 2 -agonists, intranasal drug cannot be directly compared of to a drug rates cannot in the clinical be directly trials compared of another to drug rates and in the may clinical not reflect trials the of another rates observed drug and may corticosteroids, not reflect the and rates antihistamines/decongestants observed corticosteroids, has and not antihistamines/decongestants resulted in increased frequency has not of adverse resulted reactions. in an increased No formal frequency of adverse reactions. No formal eactice. in practice. drug interaction studies have been performed drug interaction with SYMBICORT. studies have been performed with SYMBICORT. Flat Size: 7.25 in (W) Flat x 10.5 Size: in 7.25 (H) Finished (W) x 10.5 Size: in 14.5 (H) in Finished (W) x 10.5 Size: in 14.5 (H) in (W) x 10.5 in (H)