SYMBICORT SIDE EFFECTS

Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

LABA use may result in the following:

• Serious asthma-related events – hospitalizations, intubations, death
• Cardiovascular and central nervous system effects

Systemic and inhaled corticosteroid use may result in the following:

• Candida albicans infection
• Pneumonia or lower respiratory tract infections in patients with COPD
• Immunosuppression
• Hypercorticism and adrenal suppression
• Growth effects in pediatric patients
• Glaucoma and cataracts

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience In Asthma

Adult And Adolescent Patients 12 Years Of Age And Older

The overall safety data in adults and adolescents are based upon 10 active-and placebo-controlled clinical trials in which 3393 patients ages 12 years and older (2052 females and 1341 males) with asthma of varying severity were treated with SYMBICORT 80/4.5 or 160/4.5 taken 2 inhalations once or twice daily for 12 to 52 weeks. In these trials, the patients on SYMBICORT had a mean age of 38 years and were predominantly Caucasian (82%).

The incidence of common adverse events in Table 2 below is based upon pooled data from three 12-week, double-blind, placebo-controlled clinical studies in which 401 adult and adolescent patients (148 males and 253 females) age 12 years and older were treated with 2 inhalations of SYMBICORT 80/4.5 or SYMBICORT 160/4.5 twice daily. The SYMBICORT group was composed of mostly Caucasian (84%) patients with a mean age of 38 years, and a mean percent predicted FEV₁ at baseline of 76 and 68 for the 80/4.5 mcg and 160/4.5 mcg treatment groups, respectively. Control arms for comparison included 2 inhalations of budesonide HFA metered dose inhaler (MDI) 80 or 160 mcg, formoterol dry powder inhaler (DPI) 4.5 mcg, or placebo (MDI and DPI) twice daily. Table 1 includes all adverse events that occurred at an incidence of >3% in any one SYMBICORT group and more commonly than in the placebo group with twice-daily dosing. In considering these data, the increased average duration of patient exposure for SYMBICORT patients should be taken into account, as incidences are not adjusted for an imbalance of treatment duration.

Table 1 : Adverse reactions occurring at an incidence of ≥ 3% and more commonly than placebo in the SYMBICORT groups: pooled data from three 12-week, double-blind, placebo-controlled clinical asthma trials in patients 12 years and older

Treatment1	SYMBICORT		Budesonide		Formoterol	Placebo N = 400 %
Adverse Event	80/4.5 N = 277 %	160/4.5 N = 124 %	80 mcg N = 121 %	160 mcg N = 109 %	4.5 mcg N = 237 %
Nasopharyngitis	10.5	9.7	14.0	11.0	10.1	9.0
Headache	6.5	11.3	11.6	12.8	8.9	6.5
Upper respiratory tract infection	7.6	10.5 12	8.3	9.2	7.6	7.8
Pharyngolaryngeal pain	6.1	8.9	5.0	7.3	3.0	4.8
Sinusitis	5.8	4.8	5.8	2.8	6.3	4.8
Influenza	3.2	2.4	6.6	0.9	3.0	1.3
Back pain	3.2	1.6	2.5	5.5	2.1	0.8
Nasal congestion	2.5	3.2	2.5	3.7	1.3	1.0
Stomach discomfort	1.1	6.5	2.5	4.6	1.3	1.8
Vomiting	1.4	3.2	0.8	2.8	1.7	1.0
Oral Candidiasis	1.4	3.2	0	0	0	0.8
Average Duration of Exposure (days)	77.7	73.8	77.0	71.4	62.4	55.9
1. All treatments were administered as 2 inhalations twice daily.

 

Long-Term Safety -Asthma Clinical Trials In Patients 12 Years And Older

Long-term safety studies in adolescent and adult patients 12 years of age and older, treated for up to 1 year at doses up to 1280/36 mcg/day (640/18 mcg twice daily), revealed neither clinically important changes in the incidence nor new types of adverse events emerging after longer periods of treatment. Similarly, no significant or unexpected patterns of abnormalities were observed for up to 1 year in safety measures including chemistry, hematology, ECG, Holter monitor, and HPA-axis assessments.

Pediatric Patients 6 To Less Than 12 Years Of Age

The safety data for pediatric patients aged 6 to less than 12 years is based on 1 trial of 12 weeks treatment duration. Patients (79 female and 105 male) receiving inhaled corticosteroid at trial entry were randomized to SYMBICORT 80/4.5 (n=92) or budesonide pMDI 80 mcg (n=92), 2 inhalations twice daily. The overall safety profile of these patients was similar to that observed in patients 12 years of age and older who received SYMBICORT 80/4.5 twice daily in studies of similar design. Common adverse reactions that occurred in patients treated with SYMBICORT 80/4.5 with a frequency of ≥3% and more frequently than patients treated only with budesonide pMDI 80 mcg included upper respiratory tract infection, pharyngitis, headache, and rhinitis.

Clinical Trials Experience In Chronic Obstructive Pulmonary Disease

The safety data described below reflect exposure to SYMBICORT 160/4.5 in 1783 patients. SYMBICORT 160/4.5 was studied in two placebo-controlled lung function studies (6 and 12 months in duration), and two active-controlled exacerbation studies (6 and 12 months in duration) in patients with COPD.

The incidence of common adverse events in Table 3 below is based upon pooled data from two double-blind, placebo-controlled lung function clinical studies (6 and 12 months in duration) in which 771 adult COPD patients (496 males and 275 females) 40 years of age and older were treated with SYMBICORT 160/4.5, two inhalations twice daily. Of these patients 651 were treated for 6 months and 366 were treated for 12 months. The SYMBICORT group was composed of mostly Caucasian (93%) patients with a mean age of 63 years, and a mean percent predicted FEV₁ at baseline of 33%. Control arms for comparison included 2 inhalations of budesonide HFA (MDI) 160 mcg, formoterol (DPI) 4.5 mcg or placebo (MDI and DPI) twice daily. Table 2 includes all adverse events that occurred at an incidence of ≥3% in the SYMBICORT group and more commonly than in the placebo group. In considering these data, the increased average duration of patient exposure to SYMBICORT should be taken into account, as incidences are not adjusted for an imbalance of treatment duration.

Table 2 : Adverse reactions occurring at an incidence of ≥ 3% and more commonly than placebo in the SYMBICORT group: pooled data from two double-blind, placebo-controlled clinical COPD trials

Treatment1	SYMBICORT	Budesonide	Formoterol	Placebo N = 781 %
Adverse Event	160/4.5 N = 771 %	160 mcg N = 275 %	4.5 mcg N = 779 %
Nasopharyngitis	7.3	3.3	5.8	4.9
Oral candidiasis	6.0	4.4	1.2	1.8
Bronchitis	5.4	4.7	4.5	3.5
Sinusitis	3.5	1.5	3.1	1.8
Upper respiratory tract infection viral	3.5	1.8	3.6	2.7
Average Duration of Exposure (days)	255.2	157.1	240.3	223.7
1. All treatments were administered as 2 inhalations twice daily.

 

Lung infections other than pneumonia (mostly bronchitis) occurred in a greater percentage of subjects treated with SYMBICORT 160/4.5 compared with placebo (7.9% vs. 5.1%, respectively). There were no clinically important or unexpected patterns of abnormalities observed for up to 1 year in chemistry, hematology, ECG, ECG (Holter) monitoring, HPA-axis, bone mineral density and ophthalmology assessments.

The safety findings from the two double-blind, active-controlled exacerbations studies (6 and 12 months in duration) in which 1012 adult COPD patients (616 males and 396 females) 40 years of age and older were treated with SYMBICORT 160/4.5, two inhalations twice daily were consistent with the lung function studies.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of SYMBICORT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Some of these adverse reactions may also have been observed in clinical studies with SYMBICORT.

Cardiac disorders: angina pectoris, tachycardia, atrial and ventricular tachyarrhythmias, atrial fibrillation, extrasystoles, palpitations

Endocrine disorders: hypercorticism, growth velocity reduction in pediatric patients

Eye disorders: cataract, glaucoma, increased intraocular pressure

Gastrointestinal disorders: oropharyngeal candidiasis, nausea

Immune system disorders: immediate and delayed hypersensitivity reactions, such as anaphylactic reaction, angioedema, bronchospasm, urticaria, exanthema, dermatitis, pruritus

Metabolic and nutrition disorders: hyperglycemia, hypokalemia

Musculoskeletal, connective tissue, and bone disorders: muscle cramps

Nervous system disorders: tremor, dizziness

Psychiatric disorders: behavior disturbances, sleep disturbances, nervousness, agitation, depression, restlessness

Respiratory, thoracic, and mediastinal disorders: dysphonia, cough, throat irritation

Skin and subcutaneous tissue disorders: skin bruising

Vascular disorders: hypotension, hypertension