U.S. regulators concerned about the possibility of fatal overdoses on Tuesday ordered stronger warnings about overdoses with the painkilling drugs containing propoxyphene, including Darvon and Darvocet.

The Food and Drug Administration said manufacturers whose products contain propoxyphene would have to strengthen the labels and add boxed warnings that emphasize the risk for overdose.  Medication guides would also be given to each person filling or refilling a prescription.

In a statement the agency said, "FDA is taking action to reduce the likelihood of such fatal overdoses in the United States while we investigate the safety of propoxyphene more fully. In Europe, there is recent evidence that this medication may be more lethal in overdose than other pain medications."

Propoxyphene is an opioid widely used to treat mild to moderate pain and has been on the market since 1957 under the brand name Darvon and is marketed today by a wide number of generic drug makers.

Dr. Janet Woodcock, director of the U.S. Food and Drug Administration's Center for Drug Evaluation and Research, during a news conference said the manufacturers would also be required to conduct a new safety study to assess unanswered questions, such as how propoxyphene affects the heart when taken at higher-than-recommended doses.

The tougher, boxed warnings on the medicines were being called for because of reports of accidental and intentional overdoses, including some that were fatal.

Dr. Gerald Dal Pan, head of the FDA's office of surveillance and epidemiology said between 1959 and 2005, 91 deaths attributed to an overdose of these products have been recorded in the adverse-events database.

However the FDA has denied a petition from the consumer advocacy group Public Citizen asking for a phased withdrawal of products containing propoxyphene. An agency advisory panel voted 14-12 in favor of pulling the drugs from the market.

"The reason for the denial is that FDA has determined that propoxyphene is an acceptable option for relief of mild-to-moderate pain when taken as directed," Woodstock said. "Moreover, FDA recognizes that other options clinicians might have for pain management come with their own safety concerns."

The FDA said it rejected a ban because "the benefits of using the medication for pain relief at recommended doses outweighs the safety risks at this time."                                                  

The agency will further evaluate the safety of propoxyphene and take additional action if necessary, FDA officials said. The FDA is also working with several health-care organizations to collect additional safety data on these products, Woodcock said, adding that "the data we accumulate could result in additional regulatory action."