FDA Orders Stronger Warnings for Pain and Smoking Meds

The FDA recently ordered boxed warnings on labels for pain medications containing propoxyphene, as well as for the smoking cessation drugs varenicline (Chantix) and bupropion (Zyban).

The agency is requiring manufacturers of propoxyphene-containing products, such as Darvon and Darvocet, to strengthen the label to emphasize the potential for overdose. Manufacturers also will be required to provide a medication guide to patients stressing the importance of using these drugs as directed.

In an earlier petition to the FDA, the public interest group Public Citizen requested a phased market withdrawal of propoxyphene, which has been available in the United States since 1957. The FDA denied the petition, noting that the benefits of using the medication for pain relief at recommended doses outweigh the safety risks at this time. The agency is, however, requiring a new safety study assessing the effects of propoxyphene on the heart at higher-than-recommended doses. Last month, the European Medicines Agency recommended that the drug (known as dextropropoxyphene in Europe) be withdrawn from the market.

Reports of changes in behavior, depressed mood, hostility, and suicidal thoughts prompted the FDA's action on the 2 smoking cessation products, and the new boxed warnings will highlight the risk of these serious mental health events. Similar information will be required for bupropion marketed as the antidepressant Wellbutrin and for generic versions of bupropion. These drugs already carry a boxed warning for suicidal behavior in treating psychiatric disorders.

"Smoking is the leading cause of preventable disease, disability, and death in the United States, and we know these products are effective aids in helping people quit," said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research. "The risks of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking," she added. She said clinicians need to monitor patients for any unusual changes in mood or behavior after starting these drugs.

In announcing the need for new warnings, the FDA noted that neither varenicline nor bupropion contain nicotine, and some of the symptoms reported may be a response to nicotine withdrawal. In addition to the boxed warning, manufacturers will be required to conduct a clinical trial to determine how often serious neuropsychiatric symptoms occur in patients using various smoking cessation therapies, including patients who currently have psychiatric disorders.

The FDA's review of adverse events for patients using nicotine patches did not identify a clear link between those medications and suicidal events.

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