Acting on a petition from the public interest group Public Citizen, a Food & Drug Administration (FDA) advisory panel last Friday voted narrowly to recommend that a widely used opioid pain medication be removed from the market. The drug is prophoxyphene, which has been in the pharmacopeia for more than a half century, and is most widely prescribed under the brand names Darvon and Darvocet.
65 mg Darvon pills (usdoj.gov)
Prescribed for the relief of mild to moderate pain, prophoxyphene is used in dozens of generic pain medications, too. According to a briefing paper
prepared by Xanodyne Pharmaceuticals, the manufacturer of Darvon and Darvocet, some 26 million prescriptions for the pain-fighting pair were written in 2005.
The FDA approved new Darvon formulations as recently as 2003 and a generic phophoxyphen pain medication in 2005. The drug has also passed a number of FDA reviews in the past half-century, including one occasioned by another Public Citizen petition in 1978. The FDA can ban a drug if it is proven unsafe or ineffective when taken as directed.
The agency collected reports of more than 1,400 deaths in people who had taken the drug since 1957, though experts stressed the figure does not prove the drug was the cause of death in all cases. Nor does it seem an exceptionally large figure for an opioid drug prescribed millions of times a year for more than 50 years.
The panel also relied on a Florida Medical Examiner Commission report on 2007 drug-related deaths that showed 87 deaths linked to prophoxyphene.
"If that's not a risk, I don't know what is," said Dr. Sidney Wolfe, head doctor for Public Citizen.
There may be a risk, but it's relative. That same report listed 476 deaths caused by alcohol poisoning, 743 from tranquilizer overdoses, and 843 from cocaine. Among opiate-caused deaths, methadone led with 785, then Oxycontin with 705, hydrocodone with 264, morphine with 255, Fentanyl with 117, and heroin with 93 -- all greater than the number of deaths attributed to Darvon and its generic equivalents. Even the tranquilizer Meprobamate killed more people with 88 deaths listed. (Cannabis was listed as the cause of death in zero deaths.)
Still, despite weak evidence to justify removing Darvon and its brothers from the pharmacopeia, the FDA advisory panel voted to recommend that 14-12 last Friday. A final decision will come in a few weeks.
"It's not a very clear-cut picture," Sharon Hertz, MD, deputy director of the agency's analgesia drugs division, said at a press briefing after the decision. "It's not straightforward that it should or shouldn't come off the market."
Some panel members saw little benefit in keeping Darvon on the market. "I would say, little 'b', big 'r' for this drug. That's little benefit and lots of risk. And that's unsettling," said Ruth Day, PhD, who voted to remove the drug.
It "looks like it offers placebo benefits with opioid risks," saids Sean Hennessey, PhD, a panel member and epidemiologist from the University of Pennsylvania.
But other panel members warned that banning prophoxyphene could leave pain patients in the lurch. It could also drive them to other pain, more potent pain medications, like Oxycontin, they warned.
"Every drug you're talking about that's going to deal with pain has difficulty," said Mary Tinetti, MD, a professor of medicine at Yale University. "There is the possibility that the drugs that would take its place would cause at least as much harm in some people."
Xanodyne hopes it can keep the drug on the market. "I'm hoping to do everything we can to keep this product available to the 22 million people who need it," the company's vice president for clinical development and medical affairs, James Jones, told WebMD.