Rofecoxib is a non-steroidal anti-inflammatory drug (NSAID) that selectively inhibits the cyclooxygenase-2 (COX-2) enzyme [1]. This selective action is what protects the stomach compared to traditional NSAIDs.

Non-selective NSAIDs, such as ibuprofen and naproxen, inhibit both COX-1 and COX-2 enzymes. COX-1 plays a crucial role in protecting the stomach lining by producing prostaglandins, which maintain the mucosal barrier [2]. When non-selective NSAIDs inhibit COX-1, they reduce prostaglandin production, leading to an increased risk of gastrointestinal (GI) side effects, such as ulcers, bleeding, and perforation [3].

Rofecoxib, as a COX-2 selective inhibitor, primarily targets the enzyme responsible for inflammation and pain, without significantly affecting COX-1 and prostaglandin production in the stomach [1][2]. Consequently, rofecoxib has a lower risk of GI side effects compared to non-selective NSAIDs [3].

However, it is essential to note that rofecoxib was withdrawn from the market in 2004 due to an increased risk of cardiovascular events, such as heart attacks and strokes [4]. Therefore, while rofecoxib's selective action protects the stomach, its use is generally not recommended due to its cardiovascular risks.

Sources:

1. DrugPatentWatch.com. (n.d.). Rofecoxib. Retrieved from https://www.drugpatentwatch.com/drugs/rofecoxib
2. University of Washington. (n.d.). COX-1 and COX-2 Inhibitors. Retrieved from https://www.washington.edu/research/pathology/teaching/cox1-2.html
3. U.S. National Library of Medicine. (2021, May 11). Nonsteroidal anti-inflammatory drugs (NSAIDs). Retrieved from https://medlineplus.gov/nonsteroidalantiinflammatorydrugs.html
4. U.S. Food and Drug Administration. (2005, February). FDA Announces Rofecoxib (Vioxx) Withdrawal. Retrieved from https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-announces-rofecoxib-vioxx-withdrawal