Asthma inhaler Advair linked to increase in mortality from bronchial asthma

Advair, a combination of salmeterol (Serevent) and fluticasone (Flovent) is one of the best selling drugs in the world. Salmeterol is a bronchodilator which dilates the airways and fluticasone is a steroid which reduces airway inflammation. However, the drug has come under scrutiny because of a recent report that Advair may actually increase asthma deaths. The manufacturer GlaxoSmithKline, however, has rejected the findings and calls the article extremely irresponsible and riddled with inaccuracies.

Forbes magazine had in an article on 6th April, reported that "growing evidence suggests that a small percentage of patients--perhaps 4,000 people a year, by one doctor's estimate--may be dying because of Advair or its Serevent component".

It quotes Dr. Shelley Salpeter, a clinical professor of medicine at Stanford University who argues who says both Advair and Serevent should be recalled. Dr. Shelley reviewed the results of 19 previous trials of Serevent-style drugs and found that patients have twice the rate of asthma hospitalizations, twice the rate of life-threatening asthma and four times as many deaths as patients who are not on those drugs.

Apparently, Advair and Serevent cause four of every five asthma-related deaths each year. "These drugs make asthma worse," Dr. Shelley says. By some estimates, asthma kills roughly 5,000 Americans a year. This extrapolates to 4000 asthma deaths related to these drugs.

In response, Glaxo says its detractors are exaggerating the risks. "The safety and efficacy of Advair are extremely well-established with regulators and physicians across the world," A Glaxo spokeswoman said. "The data we have are inconclusive," says Kathy A. Rickard, a Glaxo vice president, echoing early responses by Wyeth about its Redux diet drug and Merck & Co. about its Vioxx painkiller.

Last month GlaxoSmithKline had reached an agreement with the U.S. regulator to update Advair's label with a new warning advising doctors to limit the use of the drug to patients who don't benefit from other asthma drugs, or who are severe cases.

Drug safety authority was aware of the dangers of TGN1412 drug trial

Before the first human trials of TGN1412, UK Government's drugs safety authority was notified that there was a risk of a catastrophic reaction. The trial left six men in intensive care after they developed a severe reaction.

TeGenero, the German manufacturer of TGN1412, had in its application to the Medicines and Healthcare Products Regulatory Authority (MHRA) reported that there had been previous incidence in which similar drugs had provoked serious adverse reaction in human volunteers. Still the MHRA allowed the trial to go ahead and six men who received the drug developed a "cytokine storm".

An interim report of the inquiry issued last Wednesday said no human error had been found in the manufacture, preparation or dose of the drug. The Investigators Brochure, which summarises evidence for the study, says: "Although not to be expected after TGN1412 administration, a cytokine release syndrome or other immunological complications may occur after infusion of TGN1412".

Tests on animals had revealed no ill effects. Apparently, the MHRA felt that TeGenero's decision to administer to volunteers a 500-fold dilution of the drug provided sufficient protection.