FDA orders new asthma drug warnings to take effect

WASHINGTON (Reuters) - U.S. health regulators have finalized new warnings for controversial inhaled asthma drugs, but exercised new powers to order the changes on products made by GlaxoSmithKline Plc and AstraZeneca Plc.

The warnings, expected since February, say medicines known as long-acting beta-agonists, or LABAs, should never be used on their own to treat asthma, Food and Drug Administration officials said on Wednesday. While some of the companies accepted the changes, the two British drugmakers resisted, agency officials said.

Glaxo’s Serevent and Novartis AG’s Foradil, which Merck & Co Inc markets in the United States, are LABA drugs. Two more widely used blockbuster medicines -- Glaxo’s Advair and AstraZeneca’s Symbicort -- are combination drugs that include a LABA with a corticosteroid.

Letters announcing the final label warning were also sent to Sepracor Inc, now part of Dainippon Sumitomo Pharma Co and the maker of Brovana, and Dey Pharma, a subsidiary of Mylan Inc that makes Perforomist, the FDA said.

“FDA is ordering the involved companies to make labeling changes capturing these new recommendations,” Dr. Badrul Chowdhury, head of the FDA’s pulmonary drugs division, told Reuters. “Not all of the companies have accepted all the changes ... so that’s where the ordering comes in.”

In a statement, Glaxo said it would work quickly to include the updated warnings but did not say why the company had objected or what specific warnings it took issue with. Representatives for Glaxo did not immediately respond to a request for further comment.

AstraZeneca said in a statement that it was confident in the “positive benefit-risk profile” of Symbicort in asthma. “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 statement said.

Wednesday’s move marks the eighth time the FDA has been forced to leverage its new power to change drug labeling since Congress granted it the authority in a 2007 law.

The label warnings are effective immediately and will be online, but it was unclear how long it would take for the new cautions to be added to actual products, the FDA said.

FDA officials initially called on doctors to halt use of LABA drugs in patients also using a steroid once their asthma was under control, but on Wednesday amended that warning to instruct doctors to wean patients off the LABAs over time in a “step down” approach.

Earlier draft warnings, including a call for children with asthma who need additional LABA drug therapy to be prescribed a combination product to ensure that the drug is not used alone, remain, the FDA said.

LABAs work by relaxing the muscles of the airways to help people breathe easier, but they can cause an increased risk of severely worse asthma symptoms that can lead to hospitalizations and death, the FDA has said.

FDA officials hope the warnings will reduce stand-alone use of LABA drugs in asthma patients, which Chowdhury said has already become an uncommon practice given the agency’s closer scrutiny of the drugs.

LABAs, which are also used to treat the more serious lung condition chronic obstructive pulmonary disease (COPD), are blockbuster products for the companies with Advair’s sales reaching about $7.8 billion in 2009, while Symbicort’s sales were about $2.3 billion.

Use of the drugs in COPD patients is not affected by the new warnings.

Sally Seymour, deputy director of FDA’s pulmonary drugs division, said the agency will monitor use of the drugs to look for any patterns and see if any future agency action is needed.

The FDA has also called on manufacturers to conduct further studies to better understand the safety of LABA drugs when used with an inhaled steroid.

In March, the agency’s outside advisers met to discuss how to conduct such studies, but Seymour said it was not yet clear when those studies would commence or how long they would take.

The FDA posted the final warning on its website at

Reporting by Susan Heavey; Editing by Leslie Gevirtz, Bernard Orr and Richard Chang