FDA Updates U.S. Product Labels for LABA-Containing Medications Including AstraZeneca's SYMBICORT

WILMINGTON, Del., June 2 /PRNewswire-FirstCall/ -- Today, the U.S. Food and Drug Administration (FDA) released final label revisions for respiratory medications that contain an active ingredient known as a long-acting beta-agonist (LABA).  This follows the FDA communication on 18 February 2010 requesting all manufacturers of LABA-containing medications to undertake class-labeling changes.

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The FDA made label revisions to both single ingredient and combination LABA-containing medications.  For the treatment of asthma, single ingredient LABAs should only be used with an asthma controller medication such as an inhaled corticosteroid (ICS), they should not be used alone.  SYMBICORT® (budesonide/formoterol fumarate dihydrate) is an asthma combination medication that contains both an ICS (budesonide) and a LABA (formoterol).  

The updated label for combination asthma medications, including SYMBICORT, provides guidance on how these products should be prescribed to treat asthma, including:

• 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.

In addition, the Boxed Warning, and other relevant sections of the label, have been revised to inform healthcare professionals and patients that LABAs, when used as single ingredient products, increase the risk of asthma-related death based on a large placebo-controlled study with salmeterol (a single ingredient LABA product).  FDA considers this risk to be a class effect of all LABAs, including formoterol, one of the components of SYMBICORT. 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.

"AstraZeneca is confident in the positive benefit-risk profile of SYMBICORT in asthma.  Combination therapies, such as SYMBICORT, continue to play a critical role in helping appropriate patients control asthma symptoms," said Dr. Cathy Bonuccelli, Vice President, Clinical Respiratory & Inflammation, AstraZeneca.  "Regular assessments of patients' asthma control by their physicians is important for ensuring that they are on the appropriate therapy based on their individual treatment needs."

In SYMBICORT clinical studies, AstraZeneca has shown that the combination of budesonide and formoterol  provides clear benefits to appropriate patients with asthma, such as improvement in asthma measures of control and quality of life.

Patients who are currently taking SYMBICORT should continue their prescribed medication, and talk to their doctor regarding any questions they may have about their treatment.

The updated label only impacts the asthma indication for SYMBICORT and does not pertain to the other approved use of SYMBICORT for chronic obstructive pulmonary disease (COPD).

To view the FDA communication, visit the following FDA Web site link: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213836.htm

Important Safety Information, including boxed WARNING

WARNING: ASTHMA RELATED DEATH

Long-acting beta2-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 beta2- 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.

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

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 long-acting inhaled beta2-agonists for any reason.

Caution should be exercised when considering the coadministration of SYMBICORT with long-term ketoconazole and other known potent CYP3A4 inhibitors.

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 cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Long-term use of orally inhaled corticosteroids, such as budesonide, a component of SYMBICORT, may affect normal bone metabolism resulting in 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.

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.

Additional Information Specific to Asthma

The most common adverse events greater than or equal to 5% reported in clinical trials included nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, and stomach discomfort.

Additional Information Specific to COPD

For patients with COPD, the approved dosage of SYMBICORT is 160/4.5 mcg, 2 inhalations twice daily.

The most common adverse events greater than or equal to 3% reported in COPD clinical trials included nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection.

Lower respiratory tract infections, including pneumonia, have been reported following the inhaled administration of corticosteroids.

In 2 placebo-controlled SYMBICORT COPD clinical studies, pneumonia did not occur with greater incidence in the SYMBICORT 160/4.5 group, compared with placebo, while the incidence of lung infections other than pneumonia (eg, bronchitis) was higher for SYMBICORT than placebo.

Indications

SYMBICORT is indicated for the treatment of asthma in patients 12 years of age and older.

SYMBICORT 160/4.5 mcg is also indicated for the maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. For patients with COPD, the approved dosage of SYMBICORT is 160/4.5 mcg two inhalations twice daily. SYMBICORT does not replace fast-acting inhalers and should not be used to treat acute symptoms of COPD or asthma. SYMBICORT should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.

Please see full Prescribing Information, including boxed WARNING, and visit www.MySYMBICORT.com.

About AstraZeneca

AstraZeneca (NYSE: AZN) is engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and in the supply of healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with global healthcare sales of $31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines.  In the United States, AstraZeneca is a $13.5 billion dollar healthcare business.  

For more information about AstraZeneca in the US or our AZ&Me™ Prescription Savings programs, please visit: www.astrazeneca-us.com.

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SOURCE AstraZeneca