• SYMBICORT 160/4.5 for the maintenance treatment of COPD and for reducing COPD exacerbations
  • SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms.

SPEED

See COPD Safety Profile.

ONSET OF EFFECT DATA

SYMBICORT 160/4.5 for the maintenance treatment of COPD

BETTER BREATHING—FAST1-3

The majority of patients’ FEV1 improvement occurred at 5 minutes in COPD1-3

5 mins Icon

In a serial spirometry subset of patients taking SYMBICORT 160/4.5* (n=121) in the SUN Study, 67% of 1-hour postdose FEV1 improvement occurred at 5 minutes on day of randomization, 83% at month 6, and 84% at end of treatment1-3

Sustained improvement in lung function was demonstrated in COPD in a 12-month efficacy and safety study1,2

*Administered as 2 inhalations twice daily.

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms

The most common adverse reactions ≥3% reported in COPD lung function clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection.

STUDY DESIGN & COMPARATOR ARMS: Lung Function Study

Study 2 (SUN): A 12-month, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 1964 patients with COPD compared SYMBICORT pMDI 160/4.5 mcg (n=494), SYMBICORT pMDI 80/4.5 mcg (n=494), formoterol 4.5 mcg (n=495), and placebo (n=481), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD and symptoms for >2 years.

The study included a 2-week run-in period followed by a 12-month treatment period. This study was designed to assess change from baseline to the average over the randomized treatment period in predose FEV1 and in 1-hour postdose FEV1. The prespecified primary comparisons for predose FEV1 were vs placebo and formoterol and the primary comparison for 1-hour postdose was vs placebo.

COMPARATOR ARMS

Mean improvement in 1-hour postdose FEV1 (mL/%) over 12 months (serial spirometry subset):

Day of randomization

SYMBICORT 160/4.5 mcg: 240 mL/26%

Formoterol 4.5 mcg: 180 mL/20%

Placebo: 40 mL/5%

6 months

SYMBICORT 160/4.5 mcg: 270 mL/28%

Formoterol 4.5 mcg: 200 mL/23%

Placebo: 60 mL/7%

End of month 12 (LOCF)

SYMBICORT 160/4.5 mcg: 240 mL/26%

Formoterol 4.5 mcg: 170 mL/19%

Placebo: 30 mL/5%

SYMBICORT 160/4.5 mcg* (n=121)

Formoterol 4.5 mcg* (n=124)

Placebo* (n=125)

*Administered as 2 inhalations twice daily.

Onset of effect data in asthma

SYMBICORT for asthma patients years of age uncontrolled on an ICS

CONTROL

See COPD Safety Profile.

EXACERBATION DATA

SYMBICORT 160/4.5 for reducing COPD exacerbations

REDUCTION IN COPD EXACERBATIONS

In a 12-month exacerbation clinical trial (Study 4), SYMBICORT 160/4.5 significantly reduced the annual rate of moderate/severe COPD exacerbations vs formoterol3,4

Annual rate estimate:
1.05, formoterol 4.5 mcg* (n=403)

Reduction in COPD Exacerbation Rate

P<.0001 vs formoterol4
Estimate Rate Ratio=0.65;
95% CI: 0.53, 0.80

Annual rate estimate:
0.68, SYMBICORT 160/4.5 mcg* (n=404)

In a second exacerbation clinical trial of 6-month duration (Study 3), SYMBICORT 160/4.5 significantly reduced the annual rate of moderate/severe COPD exacerbations by 26% vs formoterol (Estimate Rate Ratio=0.74; 95% CI: 0.61, 0.91; P=.004)3,4

Annual rate estimate was 0.94 for SYMBICORT 160/4.5 mcg* (n=606) vs 1.27 for formoterol 4.5 mcg* (n=613)

*Administered as 2 inhalations twice daily.

In Study 3, COPD exacerbations were defined as worsening of ≥2 major symptoms (dyspnea, sputum volume, sputum color/purulence) or worsening of any 1 major symptom together with ≥1 of the minor symptoms (sore throat, colds [nasal discharge and/or nasal congestion], fever without other cause, increased cough or increased wheeze) for ≥2 consecutive days. COPD exacerbation severity was classified as moderate if symptoms required systemic corticosteroid (≥3 days) and/or antibiotic treatment, and severe if symptoms required hospitalization.

In Study 4, COPD exacerbations were defined as worsening of COPD that required treatment with a course of oral steroids and/or hospitalization.

The safety findings from the two exacerbation clinical trials were consistent with the lung function studies.

STUDY DESIGN: Exacerbation Studies

Study 3 (RISE): A 6-month, Phase IIIB, randomized, double-blind, double-dummy, parallel-group, multicenter study of 1219 patients with COPD compared SYMBICORT pMDI 160/4.5 mcg (n=606) with formoterol 4.5 mcg (n=613), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD, COPD symptoms for >1 year, and a history of ≥1 moderate or severe COPD exacerbation in the previous year requiring treatment with systemic corticosteroids or hospitalization. The study included a 4-week run-in period, a 26-week randomized treatment period, and telephone follow-up 2 weeks after end of study completion. This study was designed to assess the annual rate of moderate and severe COPD exacerbations for SYMBICORT vs formoterol.

Study 4: A 12-month, Phase IIIB, randomized, double-blind, double-dummy, parallel-group, multicenter study of 811 patients with COPD compared SYMBICORT pMDI 160/4.5 mcg (n=407) with formoterol 4.5 mcg (n=404), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD, COPD symptoms for >2 years, and a history of ≥1 COPD exacerbation in the previous year treated with a course of systemic corticosteroids and/or antibiotics. The study included a 2-week run-in period, a 12-month randomized treatment period, and telephone follow-up 2 weeks after end of study completion. This study was designed to assess the annual rate of COPD exacerbations for SYMBICORT vs formoterol.

LUNG FUNCTION DATA

SYMBICORT 160/4.5 for the maintenance treatment of COPD

SUSTAINED EFFECT OVER 12 MONTHS1,2

Improvement in 1-hour postdose FEV₁ over 12 months

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms

SUN: A 12-month efficacy and safety study

  • SYMBICORT 160/4.5 significantly improved predose FEV1 averaged over the course of the study compared to placebo and formoterol, a coprimary endpoint1
  • The most common adverse reactions ≥3% reported in COPD lung function clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection

*Administered as 2 inhalations twice daily.

†Baseline is defined as the predose FEV1 value on the day of randomization.

‡Month 12, last observation carried forward.

STUDY DESIGN & COMPARATOR ARMS

Study 2 (SUN): A 12-month, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 1964 patients with COPD compared SYMBICORT pMDI 160/4.5 mcg (n=494), SYMBICORT pMDI 80/4.5 mcg (n=494), formoterol 4.5 mcg (n=495), and placebo (n=481), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD and symptoms for >2 years.

The study included a 2-week run-in period followed by a 12-month treatment period. This study was designed to assess change from baseline to the average over the randomized treatment period in predose FEV1 and in 1-hour postdose FEV1. The prespecified primary comparisons for predose FEV1 were vs placebo and formoterol and the primary comparison for 1-hour postdose was vs placebo.

COMPARATOR ARMS

Mean improvement in 1-hour postdose FEV1 (mL/%) over 12 months:

Month 1

SYMBICORT 160/4.5 mcg: 220 mL/21%

Formoterol 4.5 mcg: 170 mL/17%

Placebo: 10 mL/1%

Month 2

SYMBICORT 160/4.5 mcg: 240 mL/23%

Formoterol 4.5 mcg: 180 mL/17%

Placebo: 30 mL/3%

Month 4

SYMBICORT 160/4.5 mcg: 230 mL/22%

Formoterol 4.5 mcg: 190 mL/18%

Placebo: 50 mL/5%

Month 6

SYMBICORT 160/4.5 mcg: 220 mL/21%

Formoterol 4.5 mcg: 190 mL/18%

Placebo: 30 mL/3%

Month 9

SYMBICORT 160/4.5 mcg: 220 mL/21%

Formoterol 4.5 mcg: 180 mL/17%

Placebo: 30 mL/3%

Month 12

SYMBICORT 160/4.5 mcg: 210 mL/20%

Formoterol 4.5 mcg: 170 mL/16%

Placebo: 0 mL/0%

End of treatment

SYMBICORT 160/4.5 mcg: 200 mL/20%

Formoterol 4.5 mcg: 170 mL/17%

Placebo: 10 mL/1%

SYMBICORT 160/4.5 mcg* (n=494)

Formoterol 4.5 mcg* (n=495)

Placebo* (n=479)

*Administered as 2 inhalations twice daily.

SYMPTOM DATA

SYMBICORT 160/4.5 for the maintenance treatment of COPD

REDUCED SYMPTOM SCORES VS FORMOTEROL ALONE5

Reduction in BCSS Symptom Scores vs Formoterol Alone

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms

SUN: A 12-month efficacy and safety study

  • BCSS§ measurement was a secondary endpoint, with the primary comparison being SYMBICORT vs placebo (P<.001) for the treatment average over 12 months5

6-Month Study (SHINE) Results

  • In a 6-month study, SYMBICORT 160/4.5 reduced COPD symptom scores by 97% vs placebo (P=.01), by 23% vs formoterol (P=.351), and by 28% vs budesonide alone (P=.247)
  • BCSS§ measurement was a secondary endpoint with the primary comparison being SYMBICORT vs placebo for the treatment average over 6 months

The most common adverse reactions ≥3% reported in COPD lung function clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection

*Administered as 2 inhalations twice daily.

§The Breathlessness, Cough, and Sputum Scale (BCSS) was a secondary endpoint measured in diary cards every day before the evening dose. Patients were asked to evaluate each symptom/item on a Likert-type scale ranging from 0 to 4, with higher scores indicating a more severe manifestation of the symptom. A total symptom score is expressed as the sum of 3 item scores, with a range from 0 to 12.

||Baseline is defined as the mean of all values obtained during the last 10 days of the run-in period. Mean BCSS baseline values were 5.35 for SYMBICORT 160/4.5, 5.39 for formoterol 4.5, and 5.34 for placebo.

P values based on treatment comparison of absolute mean change from baseline for SYMBICORT vs formoterol and placebo.

STUDY DESIGN

Study 1 (SHINE): A 6-month, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 1704 patients with COPD compared SYMBICORT pressurized metered-dose inhaler (pMDI) 160/4.5 mcg (n=277), SYMBICORT pMDI 80/4.5 mcg (n=281), budesonide 160 mcg (n=275), formoterol 4.5 mcg (n=284), the free combination of budesonide 160 mcg plus formoterol 4.5 mcg (n=287), and placebo (n=300), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD and symptoms for >2 years.

The study included a 2-week run-in period followed by a 6-month treatment period. This study was designed to assess change from baseline to the average over the randomized treatment period in predose FEV1 and in 1-hour postdose FEV1. The prespecified primary comparison for predose FEV1 was vs formoterol and for 1-hour postdose was vs budesonide.

Study 2 (SUN): A 12-month, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 1964 patients with COPD compared SYMBICORT pMDI 160/4.5 mcg (n=494), SYMBICORT pMDI 80/4.5 mcg (n=494), formoterol 4.5 mcg (n=495), and placebo (n=481), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD and symptoms for >2 years.

The study included a 2-week run-in period followed by a 12-month treatment period. This study was designed to assess change from baseline to the average over the randomized treatment period in predose FEV1 and in 1-hour postdose FEV1. The prespecified primary comparisons for predose FEV1 were vs placebo and formoterol and the primary comparison for 1-hour postdose was vs placebo.

RESCUE MEDICATION USE DATA

SYMBICORT 160/4.5 for the maintenance treatment of COPD

REDUCED RESCUE MEDICATION USE6

Reduction in Rescue Medication Use Over 12 Months

SYMBICORT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms

SUN: A 12-month efficacy and safety study

  • Rescue medication use was a secondary endpoint, with the primary comparison being SYMBICORT vs placebo (P<.001)6

6-Month Study (SHINE) Results

In a 6-month study, the reduction in rescue medication use for SYMBICORT 160/4.5 vs formoterol was not significant (25% decrease, P=.280). Rescue medication use was a secondary endpoint, with the primary comparison being SYMBICORT vs placebo (P<.001). 

The most common adverse reactions ≥3% reported in COPD lung function clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection

*Administered as 2 inhalations twice daily.

Baseline is defined as the mean of all values obtained during the last 10 days of the run-in period.

#P values based on treatment comparison of absolute mean change from baseline for SYMBICORT vs formoterol and placebo.

**Treatment Average (Trt Avg) is defined as the mean of all values obtained during the double-blind treatment period.

STUDY DESIGN

Study 1 (SHINE): A 6-month, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 1704 patients with COPD compared SYMBICORT pressurized metered-dose inhaler (pMDI) 160/4.5 mcg (n=277), SYMBICORT pMDI 80/4.5 mcg (n=281), budesonide 160 mcg (n=275), formoterol 4.5 mcg (n=284), the free combination of budesonide 160 mcg plus formoterol 4.5 mcg (n=287), and placebo (n=300), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD and symptoms for >2 years.

The study included a 2-week run-in period followed by a 6-month treatment period. This study was designed to assess change from baseline to the average over the randomized treatment period in predose FEV1 and in 1-hour postdose FEV1. The prespecified primary comparison for predose FEV1 was vs formoterol and for 1-hour postdose was vs budesonide.

Study 2 (SUN): A 12-month, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 1964 patients with COPD compared SYMBICORT pMDI 160/4.5 mcg (n=494), SYMBICORT pMDI 80/4.5 mcg (n=494), formoterol 4.5 mcg (n=495), and placebo (n=481), each administered as 2 inhalations twice daily. Subjects were current or ex-smokers with a smoking history of ≥10 pack-years, aged ≥40 years with a clinical diagnosis of COPD and symptoms for >2 years.

The study included a 2-week run-in period followed by a 12-month treatment period. This study was designed to assess change from baseline to the average over the randomized treatment period in predose FEV1 and in 1-hour postdose FEV1. The prespecified primary comparisons for predose FEV1 were vs placebo and formoterol and the primary comparison for 1-hour postdose was vs placebo.

See symptom data in asthma

SYMBICORT for asthma patients years of age uncontrolled on an ICS

SAFETY PROFILE FOR SYMBICORT IN COPD

SYMBICORT 160/4.5 for the maintenance treatment of COPD and for reducing COPD exacerbations.

Incidence of Pneumonia

Physician should remain vigilant for the possible development of pneumonia in patients with COPD. There was a higher incidence of lung infections other than pneumonia in patients receiving SYMBICORT vs placebo.3

Incidence of pneumonia was not greater in the SYMBICORT 160/4.5 mcg group compared with placebo in the pooled safety data from the lung function studies (SUN and SHINE)7

    THE INCIDENCE
    OF PNEUMONIA
    IN CLINICAL TRIALS
    SYMBICORT 160/4.5 (n=771)
    3.0%
    PLACEBO (n=781)
    3.6%

Adverse reactions in COPD lung function studies 3††‡‡

Adverse reactions occurring in the COPD lung function clinical studies at an incidence of ≥3% and more commonly than placebo in the SYMBICORT group3

Adverse reactions in COPD lung function studiesAdverse reactions in COPD lung function studies

The safety findings from the 2 exacerbation clinical trials were consistent with the lung function studies.

††Combined data from 2 pivotal clinical lung function studies of patients with COPD taking SYMBICORT.

‡‡All treatments were administered as 2 inhalations twice daily.

§§Because the SUN Study did not include a budesonide arm, there are fewer patients in this treatment group.

SEE ASTHMA SAFETY PROFILE

SYMBICORT for asthma patients years of age uncontrolled on an ICS

IMPORTANT SAFETY INFORMATION

  • Use of long-acting beta2-adrenergic agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA. When LABA are used in fixed dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone
  • 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 administration of ICS
  • 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 ICS. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available ICS
  • 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 ICS 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
  • ICS may result in a reduction in growth velocity when administered to pediatric patients
  • Glaucoma, increased intraocular pressure, and cataracts have been reported following the administration of ICS, 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 ICS 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
  • The most common adverse reactions ≥3% reported in asthma clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, pharyngitis, rhinitis, 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 beta-agonists, such as formoterol, but may produce severe bronchospasm in patients with asthma
  • ECG changes and/or hypokalemia associated with nonpotassium-sparing 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 6 years and older not adequately controlled on a long-term asthma-control medication such as an ICS or whose disease warrants initiation of treatment with both an ICS and LABA (also see DOSAGE AND ADMINISTRATION).
  • 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/or emphysema, and to reduce COPD exacerbations.
  • SYMBICORT is NOT indicated for the relief of acute bronchospasm.

Please see full Prescribing Information , including Patient Information.

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