Complications and Death linked to Serevent

Washington, DCSerevent, the inhaler medication for asthmatics, and Advair, the inhaler combining Serevent and Flovent, continue to be widely prescribed despite a 13-year history of complications. Serevent, Flovent and Advair, manufactured by GlaxoSmithKline, are a wildly successful line of inhaler drugs for the company, but Serevent has been the kiss of death for too many unfortunate users.

The ethical question about this "successful" drug remains unanswered. How many deaths have to occur before a frequently helpful drug is pulled from the market? Experts continue to argue over the answer to the question.

Serevent hit the news with a splash most recently in 2006 when the Food and Drug Administration ordered an upgraded Black Box warning on its packaging that for some users, the active ingredient in the drug, salmeterol, could cause a severe asthma attack and even death.

Described as a "long-lasting beta-agonist", Serevent became available in the U.S. in 1994. Serevent causes the bronchial muscles to relax and open up. Flovent is an inhaled steroid that reduces airway inflammation, and seems to be a helpful, relatively problem-free drug. Advair combines both Serevent and Flovent in one inhaler. According to figures for the year 2005, in the U.S. Serevent was prescribed 1.7 million times, Flovent 3.5 million times and Advair 21.1 million times. The sales total for these three inhaler drugs in the U.S. was more than $4 billion. It's easy to see why Glaxo wants to keep a good thing going.

On the other hand, in a clinical trial done by Glaxo in 1993, there were 12 asthma deaths among almost 17,000 patients who used Serevent for four months, compared to four in an equivalent control group. Not statistically significant, said Glaxo. The FDA received reports of deaths among users soon after Serevent came out, but Glaxo denied any problem.

The company did, however, set up a big safety trial in 1996, aiming to track 60,000 patients on Serevent for many years. Glaxo only got 26,000 patients to participate in the study, and by 2003 reported that that 13 people in the Serevent group had died of asthma, compared to three in the control group. Statistically this meant that there would be one extra death for every 700 patients using Serevent for one year. Glaxo sent a warning to doctors, and later discontinued the trial because of the difficulty of getting volunteers to take part.

There are about 20 million asthma sufferers in the U.S., about 5.8 million of whom are children. With such large numbers of people taking Serevent and Advair, including some people who are not asthmatics but seek treatment for a bronchial cough, even a small percentage of adverse reactions means a large group of people at risk.

One expert, Shelley Salpeter, a clinical professor of medicine at Stanford University, told journalist Robert Langreth last year that as many as 4000 of the 5000 asthma deaths in the U.S. each year could be prevented if patients stopped taking Serevent-style drugs. She says that the patients taking these drugs have been found to have twice the rate of asthma hospitalizations, twice the rate of life-threatening asthma and four times as many deaths as patients who aren't on these drugs.

You have to wonder. If your doctor says you should take Serevent or Advair, how do you know for sure which group you will fall into? You could be with the majority of patients who do well with the drug. But you could also end up in an ambulance, clutching the inhaler and hoping you will get to the hospital in time to live through the ordeal