Are Black Box Warnings Simply an Easy "Out" for the FDA?

When faced with a possible danger, how much of a warning do you need? As far as the Food and Drug Administration is concerned, your tolerance for risk is pretty high. And what about its responsibility for sounding the alarm? Eh, that can wait a while.

When picking up a prescription drug from your pharmacist, you usually receive a few sheets of paper detailing how to use the medication and its possible side effects. Some warnings don’t sound so bad—nausea, loss of appetite, drowsiness. But then there are more extreme warnings…suicidal tendencies, liver failure, heart attack or even death. The text of these stronger warnings is outlined with a black square. Hopefully your doctor or pharmacist will point it out.

Called “black box warnings,” this wording is printing on drug packaging inserts after a drug has shown, through medical studies, to be quite harmful—even deadly—and the FDA deems it worthy of its strictest caution (yet seemingly not serious enough to remove it from pharmacy shelves).

For instance, Seattle Genetics Inc. announced last week that its Hodgkin lymphoma drug, Adcetris (brentuximab), will carry a box warning due to brain infection risk called progressive multifocal leukoencephalopathy (PML). This is a fatal condition that starts with memory loss, clumsiness and aphasia, an inability to communicate using language. There’s no known cure.

The box will also warn that taking Adcetris with cancer drug bleomycin may cause lung toxicity. Since it was approved in August 2011, three people have developed PML and about 2,000 people continue to take the drug.

So why doesn’t the FDA pull Adcetris off the market? According to Bloomberg estimates, Adcetris sales may surpass $275 million in 2014. Even if prescriptions wane between now and then, there’s still plenty for the drug to bring in. Will the FDA stand in the way? Not yet, it appears.

This is just one of many drugs that carries a box warning. In 2007, the FDA issued a black box warning for all antidepressants for users 18 to 24 years old who risk committing suicide when taking drugs like Paxil and Prozac and the other 37 antidepressants on the market. However, millions continue to take antidepressants, even though they’ve also been proven to cause pulmonary hypertension in babies of mothers who took them during pregnancy and triple the risk of potentially fatal falls for people with dementia living in nursing homes.

And there are many other popular drugs with black box warnings … Pfizer has a few you’ve heard of: the anti-inflammatory Celebrex, contraceptive Depo-Provera and smoking cessation drug Chantix. And although they’ve been shown to cause cardiovascular problems, bone loss and suicidal actions (respectively), they remain on the market.

A classic case of prolonging a drug’s availability through a black box warning is Avandia (rosiglitazone), used to increase the body’s sensitivity to insulin in type 2 (adult-onset) diabetes. Its risk? A 43 percent increase chance of having a heart attack. Manufacturer GlaxoSmithKline provided less-than-transparent clinical data that focused on efficacy rather than safety, which the FDA used to fast-track its approval in 1999.

Eight years later, Avandia was making more than $2 billion a year for GSK before it got a black box warning. Some experts estimate that 100,000 heart attacks can be attributed to Avandia. In November 2011, the FDA severely restricted access to the drug, making it no longer available at retail pharmacies (but not pulled from the market completely). But there was still time for GSK to rake in more than $655 million in 2009 and $355 million in 2010 in U.S. sales alone, according to the firm’s annual report. In December 2011, GSK settled an illegal marketing suit related to Avandia and other drugs for $3 billion. The drug maker still came out ahead. Way ahead.

But the bigger point is: Why isn’t the FDA acting faster? You have to wonder who the FDA is truly looking out for. The drug manufacturers? They get to continue business as usual. Americans whose hearts, livers and lives are on the line? Well, at least we get a warning.