US FDA safety alert could threaten sales of Indian salmetrol brands to treat asthma

Anti-asthma drugs containing salmetrol could face tougher challenges in Indian market as US FDA has issued strong concern about the use of long-acting beta agonists (LABAs) to treat the disease.

In its safety alerts, the U.S. Food and Drug Administration recently announced that drugs in the class of long-acting beta agonists (LABAs) should never be used alone in the treatment of asthma in children or adults.

Salmetrol containing medicines can increase the risk of severe worsening of asthma symptoms, leading to hospitalization in both children and adults and death in some patients with asthma.

In India, salmetrol- the most commonly used LABA drug)- formulations are being sold under different brand names including Azrol (Sun Pharma), Salmeter (Dr Reddy’s), Serobid (Cipla Ltd), ForAir (GSK) etc.

The drugs involved include the single agent products Serevent and Foradil and combination medications Advair and Symbicort that also contain inhaled corticosteroids.

Advair and Serevent are marketed by Collegeville, PA-based GlaxoSmithKline. Foradil is marketed by Lebanon, PA-based Novartis AG.Symbicort is marketed by Wilmington, DE-based AstraZeneca.

Advair, the combination preparation fluticasone/salmeterol is a formulation containing fluticasone propionate and salmeterol xinafoate used in the management of asthma and chronic obstructive pulmonary disease (COPD), is marketed in India under the brand name ForAir by GSK India.

Symbicort which contain combination preparation (budesonide/B) in an inahaler was pulled back in India after launching it in the country in November 2003.

Salmetrol manufacturers will be required to include this warning in the product labels of these drugs, along with taking other steps to reduce the overall use of these medications.

These new requirements are based on US FDA analyses of clinical trials showing that use of these long-acting medicines is associated with an increased risk of severe worsening of asthma symptoms, leading to hospitalization in both children and adults and death in some patients with asthma.

These medications improve a patient’s ability to breathe freely and reduce the symptoms of asthma by relaxing muscles in the lung’s airways.

US FDA will now require that the product labels reflect the following:

* The use of LABAs is contraindicated without the use of an asthma controller medication such as inhaled corticosteroid. Single-agent LABAs should only be used in combination with an asthma controller medication; they should not be used alone

* LABAs should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medications

* LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved. Patients should then be maintained on an asthma controller medication

* Pediatric and adolescent patients who require a LABA in addition to an inhaled corticosteroid should use a combination product containing both an inhaled corticosteroid and a LABA to ensure compliance with both medications.

“Although these medicines play an important role in helping some patients control asthma symptoms, our review of the available clinical trials determined that their use should be limited, whenever possible, due to an increased risk of asthma exacerbations, hospitalizations and death,” said Badrul Chowdhury, M.D., director of the Division of Pulmonary and Allergy Products in the FDA’s Center for Drug Evaluation and Research.

The risks of hospitalization and poor outcomes are of particular concern for children; parents need to know that their child with asthma should not be on a LABA alone, according to US FDA’s Office of Pediatric Therapeutics.

LABAs are approved to treat both people with asthma or with chronic obstructive pulmonary disease (COPD). The new recommendations only apply to the use of LABAs in the treatment of asthma.

The FDA will be requiring the manufacturers of LABAs to conduct additional studies to further evaluate the safety of LABAs when used in combination with inhaled corticosteroids. The FDA will seek input on the design of these studies at a public advisory committee meeting in March 2010.

In addition to these actions, FDA will work with public and private partners under the agency’s ongoing Safe Use Initiative to study LABA prescribing practices.

Advair is marketed by GlaxoSmithKline under various trade names including Advair (US, CA), Seretide (EU, Australia), Viani (Germany), Adoair (Japan).

Advair, the leading product in the LABA segment, generated 4.98 billion pounds ($7.7 billion) in sales for Glaxo last year. Patents of Advair are set to expire on 2010.

Symbicort has sales of 1.47 billion pounds.