WASHINGTON, July 7 — The FDA has called for a boxed warning regarding overdose risk with propoxyphene-containing painkillers (Darvocet, Darvon) but will not require their withdrawal from the market.

The agency also ordered manufacturers to undertake a study to investigate evidence of higher than expected fatality rates with propoxyphene overdose compared with other analgesics and possible cardiotoxicity beyond the recommended doses.

However, the FDA rejected a petition from the consumer group Public Citizen calling for phased withdrawal of these products.

The agency’s action, which was announced during a press briefing today, did not follow the recommendation of an FDA advisory panel, which voted 14-12 to ban propoxyphene products because of overdose risk and doubts about analgesic efficacy. (See FDA Panel Calls for Propoxyfene Withdrawal)

Some pain specialists, like Lloyd Saberski, MD, of the Yale-New Haven Hospital, criticized propoxyphene as a weak narcotic.

“There is no legitimate medical advantage to keeping propoxyphene available,” Dr. Saberski said. “You are much better off using small amounts of a potent narcotic; there will be little in the way of side effects.”

Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, defended propoxyphene as an effective treatment option with efficacy beyond that offered by acetaminophen (Tylenol) alone.

“All current pharmacologic options for pain have significant liability,” she said in a media briefing. “Given the data currently available to the FDA, propoxyphene is an acceptable choice for the treatment of mild to moderate pain when it’s taken as directed.”

Today’s announcement comes just a week after an FDA advisory panel recommended a black box warning for prescription products containing acetaminophen. That panel also voted by a narrow margin to recommend that the FDA pull prescription acetaminophen-containing analgesics from the market. (See FDA Panel Backs ‘Black Box’ Warning for Acetaminophen Prescription Combos and Drug Companies Defend Acetaminophen as FDA Considers Restrictions)

Propoxyphene-containing analgesics may have fewer adverse effects than other options for mild to moderate pain in older patients when nonsteroidal anti-inflammatory drugs are inappropriate, said Sharon H. Hertz, MD, also of the Center for Drug Evaluation and Research.

They don’t have the same constipation risk as codeine-containing agents or the confusion and sedation risk of hydrocodone-containing analgesics, she said, noting that the American Geriatrics Society has discouraged use of NSAIDs in the elderly. (See NSAID, COX-2 Use Discouraged for Geriatric Pain)

This assessment drew sharp remarks from Sidney M. Wolfe, MD, acting president of Public Citizen.

“The agency has decided to allow the continued marketing of a drug with the most patient-unfavorable ratio of risks of any drug I have ever seen,” he said. “We will either appeal this anti-public health decision to the new FDA commissioner or argue in federal court that the decision was arbitrary and capricious.”

The FDA decided instead to attempt to mitigate the risks while keeping this treatment option open for patients.

The agency will require manufacturers of these drugs to provide a medication guide with all prescriptions and refills stressing the importance of taking the drugs as directed to reduce overdose risk.

In addition, Dr. Woodcock said there are plans under way with CMS and the VA system to conduct additional studies, including a study into the safety and prescribing patterns of propoxyphene among the elderly, specifically with regard to the rates of fatalities and hip fractures.

The FDA will also analyze a review of medical examiner data in the Substance Abuse and Mental Health Administration’s Drug Abuse Warning Network (DAWN).

So far, there’s been little data available on overdose since intentional overdoses are typically not reported to the FDA, said Gerald Dal Pan, MD, of its Center for Drug Evaluation and Research.

Over a 35-year period, 91 deaths related to propoxyphene have been reported to the FDA. But most were suicide attempts with multiple drugs, so it’s hard to establish a direct causal role for propoxyphene, Dr. Dal Pan said.

Related Article(s):

• FDA Panel Calls for Propoxyphene Withdrawal
• FDA Panel Backs ‘Black Box’ Warning for Acetaminophen Prescription Combos
• Drug Companies Defend Acetaminophen as FDA Considers Restrictions
• NSAID, COX-2 Use Discouraged for Geriatric Pain