RECENT MAJOR CHANGES

Boxed Warning May 2010

Indications and Usage, Treatment of Asthma (1.1)May 2010

Dosage and Administration, Asthma (2.1) May 2010

Warnings and Precautions, Asthma-Related Death (5.1) May 2010

INDICATIONS AND USAGE

SYMBICORT is a combination product containing a corticosteroid and a long-acting beta2-adrenergic agonist indicated for:

• Treatment of asthma in patients 12 years of age and older. (1.1)

• Maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema. (1.2)

Important limitations:

• Not indicated for the relief of acute bronchospasm. (1.1, 1.2)

DOSAGE AND ADMINISTRATION

For oral inhalation only.

• Treatment of asthma in patients >12 years: 2 inhalations twice daily of SYMBICORT 80/4.5 or 160/4.5. Starting dosage is based on asthma severity. (2.1)

• Maintenance treatment of airflow obstruction in COPD: 2 inhalations of SYMBICORT 160/4.5 twice daily (2.2)

DOSAGE FORMS AND STRENGTHS

Metered-dose inhaler containing a combination of budesonide (80 or 160 mcg) and formoterol (4.5 mcg) as an inhalation aerosol (3)

CONTRAINDICATIONS

• Primary treatment of status asthmaticus or acute episodes of asthma or COPD requiring intensive measures. (4)

• Hypersensitivity to any of the ingredients in SYMBICORT (4)

WARNINGS AND PRECAUTIONS

• Asthma-related death: Long-acting beta2-adrenergic agonists increase the risk. Prescribe only for recommended patient populations. (5.1)

• Deterioration of disease and acute episodes: Do not initiate in acutely deteriorating asthma or to treat acute symptoms. (5.2)

• Use with additional long-acting beta2-agonist: Do not use in combination because of risk of overdose. (5.3)

• Localized infections: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically for signs of adverse effects on the oral cavity. Advise patients to rinse the mouth following inhalation. (5.4)

• Pneumonia: Increased risk in patients with COPD. Monitor patients for signs and symptoms of pneumonia and other potential lung infections. (5.5)

• Immunosuppression: Potential worsening of infections (e.g., existing tuberculosis, fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. (5.6)

• Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from oral steroids. Taper patients slowly from systemic corticosteroids if transferring to SYMBICORT. (5.7)

• Hypercorticism and adrenal suppression: May occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue SYMBICORT slowly. (5.8)

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. Exercise caution when used with SYMBICORT. (5.9)

• Paradoxical bronchospasm: Discontinue SYMBICORT and institute alternative therapy if paradoxical bronchospasm occurs. (5.10)

• Patients with cardiovascular or central nervous system disorders: Use with caution because of beta-adrenergic stimulation. (5.12)

• Decreases in bone mineral density: Assess bone mineral density initially and periodically thereafter. (5.13)

• Effects on growth: Monitor growth of pediatric patients. (5.14)

• Glaucoma and cataracts: Close monitoring is warranted. (5.15)

• Metabolic effects: Be alert to eosinophilic conditions, hypokalemia, and hyperglycemia. (5.16, 5.18)

• Coexisting conditions: Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. (5.17)

ADVERSE REACTIONS

Most common adverse reactions (incidence > 3%) are:

• Asthma: nasopharyngitis, headache, upper respiratory tract infection, pharygolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis. (6.1)

• COPD: nasopharyngitis, oral candidiasis, bronchitis, sinusitis, upper respiratory tract infections. (6.2)

To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects.

• Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of formoterol on vascular system. (7.2)

• Beta-blockers: Use with caution. May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. (7.3)

• Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with nonpotassium-sparing diuretics may worsen with concomitant beta-agonists. (7.4)

USE IN SPECIFIC POPULATIONS

Hepatic impairment: Monitor patients for signs of increased drug exposure. (8)