Painkiller May Be Banished After Half a Century

In recent years, there has been an increasing number of drugs pulled from the market, and many observers have been blaming the drug approval process of an understaffed, underfunded, industry-dependent US Food and Drug Administration (FDA). But even old drugs, predating today’s FDA environment, also are subject to recall.

Now the FDA may consider shelving Darvon, a painkiller first approved half a century ago. An FDA advisory panel, by a narrow 14-12 vote, determined that the benefits of the drug do not outweigh the risks, and recommended pulling it from the market. The FDA often takes an advisory committee’s advice, but not always.

The consumer watchdog group Public Citizen has long fought the marketing of Darvon – which has the generic name propoxyphene hydrochloride – as well as a version of the drug frequently sold under the trade name Darvocet. The group has filed petitions and lawsuits in opposition to its ongoing availability.

Darvon, which has been on the market since 1957 in the United States, is not a first-choice painkiller. “It’s not on many formularies any longer,” says Lori Reisner, PharmD, a UCSF clinical pharmacist and painkiller specialist. “It’s still prescribed, probably most often by practitioners who have used it a long while and are comfortable with it.”

Physicians sometimes prescribe it for patients who suffer intolerable nausea or constipation due to opioids, Reisner says, but these opioid side effects often can be managed.

Darvon has a narrow therapeutic window, Reisner notes, meaning that the difference between an effective dose and a toxic dose is relatively small. Overdoses may lead to liver or other organ toxicity. “It’s considered less effective than many alternatives that are available,” Reisner says, comparable to generally safe alternatives such as codeine or tramadol.

Darvon can worsen mental depression and increase nervous system depression in combination with other agents such as alcohol, according to Reisner. Acute accidental overdoses have been known to disturb normal heart rhythm.

The FDA database of adverse events is reported to include more than 1,000 deaths – including suicides, intentional and unintentional drug overdoses, and heart attacks –associated with this class of drugs.

The FDA recently appointed Sidney Wolfe, MD, who helped lead Public Citizen’s opposition to the drug, to a four-year term on the agency’s Drug Safety and Risk Management Advisory Committee. Wolfe is slated to deliver the UCSF Chancellor’s Health Policy Lecture on Tuesday, Feb. 24, in Cole Hall at noon.

Related Links:

Ban on Painkiller Darvon Is Recommended to FDA
New York Times, Jan. 30, 2009

The FDA’s Big Bad Wolfe
Forbes.com, Jan. 21, 2009