In clinical studies, adverse events (regardless of causality) occurring at an incidence of ≥3% and more commonly than with placebo*†
SYMBICORT has safety data in studies of up to 1 year
In patients‡ taking up to twice the maximum daily dose for up to 1 year, studies demonstrated no significant or unexpected patterns of abnormalities
- Chemistry
- Hematology
- Holter monitor
- Hypothalamic pituitary adrenal (HPA)-axis assessments
- Electrocardiogram (ECG)
The maximum daily recommended dose is 640/18 mcg budesonide/formoterol (given as 2 inhalations of SYMBICORT 160/4.5 twice daily) for patients 12 years and older. Do not use more than twice daily or use a higher number of inhalations (more than 2 inhalations twice daily) of the prescribed strength of SYMBICORT as this will result in a daily dose of formoterol in excess of the dose determined to be safe. For all patients, consideration should be given to titrating to the lowest effective strength after adequate asthma stability has been achieved.
SYMBICORT should not be used more often or at higher doses than recommended. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma.
It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear in a small number of patients, particularly at higher doses.
There was a robust evaluation of the cardiac safety profile of SYMBICORT
2152 patients were evaluated in five 12-week, active- and placebo-controlled studies.
- No patient had a QT or QTc value ≥500 msec during treatment
553 patients taking SYMBICORT had evaluable continuous 24-hour Holter monitoring in 3 placebo-controlled studies involving 1232 patients.
- No important differences in occurrence of ventricular or supraventricular ectopy and no evidence of increased risk for clinically significant dysrhythmia in the group receiving SYMBICORT, compared with placebo
SYMBICORT like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Beta-agonists have been reported to produce electrocardiogram changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown.
SYMBICORT should be used with caution in patients with cardiovascular disorders. Some patients may experience an increase in blood pressure or heart rate.
*All treatments were administered as 2 inhalations twice daily.
†The incidence of common adverse events in the table above is based upon three 12-week, double-blind, placebo-controlled US clinical trials in which 401 adult and adolescent patients aged 12 years and older were treated twice daily with 2 inhalations of SYMBICORT 80/4.5 mcg or SYMBICORT 160/4.5 mcg, budesonide HFA metered-dose inhaler (MDI) 80 or 160 mcg, formoterol dry powder inhaler (DPI) 4.5 mcg, or placebos (MDI and DPI).
‡≥12 years of age with asthma.
Updated Important Safety Information, including boxed WARNING
- WARNING: Long-acting beta2-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
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.
Patients who are receiving SYMBICORT should not use additional formoterol or other LABA for any reason.
Due to possible immunosuppression, potential worsening of infections could occur; a more serious course of chickenpox or measles can occur in susceptible patients.
Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. SYMBICORT, like all products containing sympathomimetic amines, should be used with caution in patients with convulsive disorders, thyrotoxicosis, and cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Beta-adrenergic agonist medications may produce hypokalemia and hyperglycemia in some patients. As with other inhaled medications, paradoxical bronchospasm may occur with SYMBICORT. Use with caution in patients with diabetes mellitus.
Long-term use of orally inhaled corticosteroids, such as budesonide, a component of SYMBICORT, may result in a reduction in growth velocity and/or a loss of bone mineral density.
Glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids, including budesonide, a component of SYMBICORT.
In rare cases, patients on inhaled corticosteroids may present with systemic eosinophilic conditions.
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. Caution should also be exercised in patients on long-term ketoconazole and other known potent CYP3A4 inhibitors.
The most common adverse reactions ≥ 3% reported in clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis.
Indications
SYMBICORT is indicated for the treatment of asthma in patients 12 years and older (also see boxed WARNING).
SYMBICORT is NOT indicated for the relief of acute bronchospasm and should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma.
Please see full Prescribing Information
, including boxed WARNING.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call
1-800-FDA-1088.
This product information is intended for US health care professionals only.
