Rofecoxib

• Rofecoxib was a selective COX-2 inhibitor used to treat pain and inflammation.
• It was prescribed for conditions such as osteoarthritis, rheumatoid arthritis, acute pain, and dysmenorrhea.
• Common side effects included gastrointestinal issues, while serious risks involved cardiovascular events like heart attack and stroke.
• The drug was voluntarily withdrawn from the market in 2004 by its manufacturer due to evidence of increased cardiovascular risk.

What is Rofecoxib: Drug Class, Mechanism, and Uses

Rofecoxib is a medication that was classified as a selective cyclooxygenase-2 (COX-2) inhibitor, a type of nonsteroidal anti-inflammatory drug (NSAID). The rofecoxib drug class and mechanism involved selectively blocking the COX-2 enzyme, which is primarily responsible for producing prostaglandins that mediate pain and inflammation. Unlike traditional NSAIDs that inhibit both COX-1 and COX-2, rofecoxib was designed to spare COX-1, an enzyme involved in protecting the stomach lining and regulating platelet function. This selectivity was initially thought to reduce the gastrointestinal side effects commonly associated with non-selective NSAIDs.

Regarding what is rofecoxib used for, it was prescribed for the management of various painful and inflammatory conditions. Its primary indications included the symptomatic treatment of osteoarthritis, rheumatoid arthritis, and acute pain. Additionally, it was used for the treatment of primary dysmenorrhea (menstrual pain). The drug’s efficacy in reducing pain and inflammation made it a popular choice for patients seeking relief from chronic and acute musculoskeletal conditions.

Rofecoxib Side Effects and Risks

While effective in managing pain and inflammation, rofecoxib side effects and risks were a significant concern, ultimately leading to its withdrawal. Like other NSAIDs, rofecoxib could cause gastrointestinal issues such as stomach upset, nausea, and abdominal pain. Although initially believed to have a lower risk of serious gastrointestinal events (like ulcers and bleeding) compared to non-selective NSAIDs, these risks were still present.

More critically, serious cardiovascular risks emerged with rofecoxib use. These included an increased risk of myocardial infarction (heart attack) and stroke. Other potential side effects included:

• Hypertension (high blood pressure)
• Peripheral edema (swelling in the ankles and feet)
• Kidney problems, including acute kidney injury
• Liver problems, such as elevated liver enzymes
• Allergic reactions, including skin rashes and, rarely, severe anaphylaxis

The cardiovascular safety profile became the primary concern, particularly after clinical trial data revealed a statistically significant increase in thrombotic cardiovascular events in patients taking rofecoxib compared to placebo or other NSAIDs. For instance, studies showed that patients on rofecoxib had approximately twice the risk of serious cardiovascular events compared to those on placebo, as highlighted in research published in prominent medical journals.

Why Was Rofecoxib Withdrawn from the Market?

The primary rofecoxib withdrawal from market reasons stemmed from mounting evidence of increased cardiovascular risk. The drug, marketed as Vioxx, was voluntarily pulled from the global market by its manufacturer, Merck & Co., on September 30, 2004. This decision followed the results of the “APPROVe” (Adenomatous Polyp Prevention on Vioxx) trial, which was designed to evaluate the drug’s effectiveness in preventing colon polyps.

The APPROVe trial, a long-term study, revealed that patients taking rofecoxib for more than 18 months had a significantly increased risk of serious cardiovascular events, including heart attacks and strokes, compared to those taking a placebo. This finding corroborated earlier concerns raised by the VIGOR (Vioxx Gastrointestinal Outcomes Research) study, which had also indicated an elevated risk of myocardial infarction, though its initial interpretation was debated. The cumulative evidence from these and other studies demonstrated a clear and unacceptable cardiovascular safety profile, leading to the manufacturer’s decision to withdraw the drug to protect public health. The withdrawal of rofecoxib had a profound impact on drug development and regulatory oversight for other COX-2 inhibitors and NSAIDs.