Risk of Problems from Asthma Drugs Lead to New FDA Warnings

Federal regulators have moved to restrict the use of Advair, Symbicort, Foradil and Serevent, after determining that side effects of the asthma drugs may increase the risk of severe asthma problems and death in both adults and children.

On February 18, the FDA indicated that Advair, Symbicort, Foradil and Serevent should never be used alone in the treatment of asthma in children and adults. The agency is contraindicating the drugs for solo use and requiring manufacturers to create risk management strategies to educate and train health care professionals and patients about the risks of using the drugs for long-term asthma treatment.

The decision comes after an FDA analysis of a number of studies on the drugs, which are known as long-acting beta agonists (LABAs). The review was undertaken after studies raised concerns that long-term use of LABAs could cause a worsening of asthma symptoms and death in some users. Foradil, Severent, Symbicort and Advair side effects can mask worsening inflammation in the airways, the FDA determined, and worsening asthma symptoms may not be recognized in a timely manner, potentially leading to severe health risks and death.

Advair (salmeterol and fluticasone) and Serevent (salmeterol) are manufactured by GlaxoSmithKline PLC. Foradil (formoterol) is made by Novartis AG and marketed in the U.S. by Schering-Plough Corp. Symbicort is manufactured by AstraZeneca. Advair is the biggest seller out of the four drugs, with sales of nearly $7 billion annually.

In December 2008, an FDA advisory panel recommended a Foradil and Serevent should no longer be approved for asthma treatment. However the panel did not make the same recommendations for Advair and Symbicort, because the drugs are combination products that include a corticosteroid medication.

The FDA decision on Thursday means that the labels of all four drugs will state that LABAs are contraindicated without the use of an asthma controller medication, like an inhaled corticosteroid. The drugs will also include label warnings indicating that they should be used for the shortest duration possible and then discontinued, and that they should only be considered for long-term asthma treatment by patients whose asthma cannot be adequately controlled by other medications.

In addition to the label changes, the manufacturers will be required to create a risk management strategy (REMS) outlining a plan to minimize the health risks to patients. The companies will have to make a revised medication guide for patients and will have to create education plans to ensure that health care professionals are well-informed about the appropriate use of LABAs.

“The risks of hospitalization and poor outcomes are of particular concern for children,” said the FDA Office of Pediatric Therapeutics Director Dianne Murphy.” Parents need to know that their child should not be on a LABA alone.”

Asthma affects 20 million Americans, including 6.5 million children. It is a chronic disease with symptoms like wheezing, difficulty breathing and spasms, which can severely limit activities and impact quality of life.