Safety Issues May Be Slow to Surface

What can we learn from the Darvon debacle? The popular prescription pain killer propoxyphene has been sold since 1957. At one time the names Darvon and Darvocet were household names. They were perceived as really powerful analgesics.
Even though the drug has been available generically for years, it is still widely prescribed. In 2009 over 17 million bottles of propoxyphene were dispensed, making it one of the more commonly prescribed generic drugs on the market.
Despite its reputation, consumer health advocates have maintained for decades that propoxyphene was not a very effective pain reliever and carried significant risks. Sidney Wolfe, MD, of Public Citizen’s Health Research Group has been calling for restrictions for more than thirty years. In 2006 the group called for its outright removal after the drug was banned in Britain.
The FDA resisted efforts to limit sales of propoxyphene and even went against a recommendation from its own panel of experts in July of 2009. Finally, though, the agency could no longer ignore evidence that the drug causes harm. A heart study revealed that “the drug puts patients at risk of abnormal or even fatal heart rhythm abnormalities,” according to John Jenkins, MD, director of FDA’s Office of New Drugs. Last month the agency banned sales of propoxyphene.
What took so long? According to Dr. Wolfe, animal studies revealed heart toxicity decades ago. He estimates that at least 1,000 people in the U.S. died while taking propoxyphene during the last five years. Goodness knows how many died over the 50 plus years the drug was on the market.
This isn’t the first time the FDA has been slow to respond to safety threats posed by popular medications. Phenylpropanolamine (PPA) was marketed in the 1960s as a nonprescription nasal decongestant and diet pill. By the late 1970s and early 1980s physicians were detecting problems with PPA. Reports of high blood pressure and stroke were worrisome.
Despite such red flags, the FDA left PPA on the market and deferred final decisions on its safety both in 1985 and 1994. Finally, the agency acted in 2000 after a Yale study confirmed that the drug was causing bleeding strokes. The FDA asked companies to remove PPA from their products, but it took several more years to finalize the rules eliminating the drug from the market.
A prescription diet pill, fenfluramine, was introduced in 1973. It didn’t attract much attention until the 1990s when the combination Phen-Fen became very popular. Heart and lung problems were eventually detected and led to the withdrawal of fenfluramine in 1997.
Other drugs that have made headlines and have been withdrawn after years on the market include pain relievers like Bextra and Vioxx, allergy medicines like Seldane and Hismanal and the cholesterol-lowering drug Baycol. In each case, thousands of people suffered before the FDA figured out there was a problem.
What can we learn from these tragic examples? Even though the law requires all drugs be proven “safe and effective” before FDA approval, it can take decades for the agency to discover that a drug puts patients at an unacceptable risk. Physicians and patients need to realize that the FDA is fallible and that they need to be vigilant for any signs of trouble.