The Role of the FDA in Post-Marketing Safety
The U.S. Food and Drug Administration (FDA) approves drugs based on clinical trials, but some risks only become apparent after a medication is used by a larger population over time [1.8.3]. The FDA's post-marketing surveillance system monitors adverse event reports from patients and healthcare professionals [1.8.3]. If a drug is found to be defective or potentially harmful, the FDA can request or, in some cases, mandate a recall [1.8.4]. A company may also voluntarily withdraw a product [1.8.1]. This crucial oversight has led to the removal of several widely used pain medications.
The Rise and Fall of COX-2 Inhibitors: Vioxx and Bextra
COX-2 inhibitors were a class of nonsteroidal anti-inflammatory drugs (NSAIDs) designed to be gentler on the stomach than older NSAIDs. However, some of the most prominent drugs in this class were withdrawn due to serious cardiovascular risks [1.3.6].
Rofecoxib (Vioxx) Marketed by Merck, Vioxx was a blockbuster painkiller approved in 1999 [1.3.2, 1.3.7]. It was incredibly popular for treating arthritis and other acute pain. However, concerns about its safety mounted. In 2004, a clinical trial revealed that Vioxx doubled the risk of heart attack and stroke in patients who had been taking it for 18 months or more [1.3.4, 1.3.7]. Following these findings, Merck announced a worldwide voluntary withdrawal of the drug on September 30, 2004 [1.3.2]. It's estimated that Vioxx may have been linked to between 88,000 and 139,000 heart attacks in the five years it was on the market [1.3.5].
Valdecoxib (Bextra) Following the Vioxx recall, scrutiny fell upon other COX-2 inhibitors. Bextra, made by Pfizer, was another popular drug in this class. In April 2005, the FDA asked Pfizer to voluntarily withdraw Bextra from the market [1.4.1]. The decision was based on an unfavorable risk-benefit profile, which included an increased risk of heart attack and stroke, particularly in patients who had recently undergone coronary artery bypass surgery [1.4.4, 1.4.7]. Additionally, Bextra was linked to reports of rare but serious and potentially life-threatening skin reactions [1.4.4].
Withdrawal of a Long-standing Opioid: Propoxyphene
Propoxyphene was an opioid pain reliever that had been on the market since 1957, sold under brand names like Darvon and, in combination with acetaminophen, as Darvocet [1.2.3, 1.5.5]. It was prescribed for mild to moderate pain for decades.
In November 2010, the FDA requested that all manufacturers voluntarily remove propoxyphene-containing products from the U.S. market [1.5.1]. This decision was prompted by new data from a clinical study showing that the drug could cause serious and sometimes fatal heart rhythm abnormalities, even when taken at the recommended therapeutic doses [1.5.1, 1.5.2, 1.5.3]. By the time of the U.S. withdrawal, the drug had already been banned in the United Kingdom and the European Union for years due to concerns over fatal overdoses [1.2.7].
Other Notable Withdrawals
Another example is Bromfenac (Duract), an NSAID approved in 1997 for the short-term management of acute pain (10 days or less) [1.6.1]. It was voluntarily withdrawn by its manufacturer in 1998 after post-marketing reports revealed cases of severe liver failure, some requiring transplants or resulting in death, in patients who used the drug for longer than the recommended period [1.6.1, 1.6.4].
| Drug Name (Generic) | Brand Name(s) | Drug Class | Year of Withdrawal | Primary Reason for Withdrawal |
|---|---|---|---|---|
| Rofecoxib | Vioxx | COX-2 Inhibitor | 2004 | Increased risk of heart attack and stroke [1.2.4, 1.3.3]. |
| Valdecoxib | Bextra | COX-2 Inhibitor | 2005 | Increased cardiovascular risk and serious skin reactions [1.4.1, 1.4.4]. |
| Propoxyphene | Darvon, Darvocet | Opioid | 2010 | Serious heart rhythm abnormalities (cardiac toxicity) [1.5.1, 1.5.2]. |
| Bromfenac | Duract | NSAID | 1998 | Severe liver failure when used long-term [1.6.1, 1.6.4]. |
Conclusion: Lessons in Drug Safety
The history of withdrawn pain medications underscores the vital importance of ongoing, post-market safety monitoring. While drugs are approved based on the best available evidence at the time, new risks can emerge once they are used by millions of people. These recalls have led to stricter labeling requirements, including "black box" warnings on all prescription NSAIDs highlighting cardiovascular and gastrointestinal risks [1.3.6, 1.4.1]. They also serve as a critical reminder for patients and healthcare providers to have open discussions about the risks and benefits of any medication and to explore a wide range of pain management strategies, including non-pharmacological options like physical therapy, exercise, and mindfulness techniques [1.7.1, 1.7.4].
For the latest information on drug recalls, you can visit the FDA's website.
