Xanodyne Pharmaceuticals Inc., the maker Darvon and Darvocet
-- the brand version of the prescription pain medication propoxyphene -- has
agreed to withdraw the medication from the U.S. market.
The move comes at the request of the Food and Drug
Administration (FDA), which has also informed the generic manufacturers of
propoxyphene-containing products of Xanodyne's decision and requested that they
voluntarily remove their products as well.
Risk of heart problems
The FDA sought market withdrawal of propoxyphene after
receiving new clinical data showing the drug puts users at risk of potentially
serious or even fatal heart rhythm abnormalities. As a result of these data --
combined with other information, including new epidemiological data -- the
agency concluded that the risks of the medication outweigh the benefits.
"The FDA is pleased by Xanodyne's decision to voluntarily
remove its products from the U.S. market," said John Jenkins, M.D., director of
the Office of New Drugs in FDA's Center for Drug Evaluation and Research
(CDER). "These new heart data significantly alter propoxyphene's risk-benefit
profile. The drug's effectiveness in reducing pain is no longer enough to
outweigh the drug's serious potential heart risks."
Doctors notified
The FDA is advising health care professionals to stop
prescribing propoxyphene to their patients. Anyone currently taking the drug
should contact his or her health care professional as soon as possible to
discuss switching to another pain management therapy.
Propoxyphene is an opioid used to treat mild to moderate
pain. First approved by the FDA in 1957, the drug is sold by prescription under
various names both alone (e.g., Darvon) or in combination with acetaminophen
(e.g., Darvocet).
New information
Since 1978, the FDA has received two requests to remove
propoxyphene from the market. Until now, the agency had concluded that the
benefits of propoxyphene for pain relief at recommended doses outweighed the
safety risks of the drug.
In January 2009, the FDA held an advisory committee meeting
to address the efficacy and safety of propoxyphene. After considering the data
submitted with the original drug applications for propoxyphene, as well as
subsequent medical literature and postmarketing safety databases, the committee
voted 14 to 12 against the continued marketing of propoxyphene products.
In making this recommendation, the committee noted that
additional information about the drug's cardiac effects would be relevant in
weighing its risks and benefits.
European precedent
In June 2009, the European Medicines Agency (EMEA)
recommended that the marketing authorizations for propoxyphene be withdrawn
across the European Union. A phased withdrawal of propoxyphene is underway.
In July 2009, the FDA decided to permit continued marketing,
but required that a new boxed warning be added to the drug label alerting
patients and health care professionals to the risk of a fatal overdose. In
addition, the agency required Xanodyne to conduct a new safety study assessing
unanswered questions about the effects of propoxyphene on the heart.
Further review
The agency now has reviewed the data from that study, which
show that, even when taken at recommended doses, propoxyphene causes
significant changes to the electrical activity of the heart. These changes,
which can be seen on an electrocardiogram (EKG), can increase the risk for
serious abnormal heart rhythms that have been linked to serious adverse
effects, including sudden death.
The available data also indicate that the risk of adverse
events for any particular patient (even patients who have taken the drug for
many years) is subject to change based on small changes in the health status of
the patient, such as dehydration, a change in medications, or decreased kidney
function.
"With the new study results, for the first time we now have
data showing that the standard therapeutic dose of propoxyphene can be harmful
to the heart," said Gerald Dal Pan, M.D., M.H.S., director of the Office of
Surveillance and Epidemiology, CDER. "However, long-time users of the drug need
to know that these changes to the heart's electrical activity are not
cumulative. Once patients stop taking propoxyphene, the risk will go away."
Xanodyne is based in Newport, Ky.
