Rofecoxib: clinical pharmacology and clinical experience

BACKGROUND: Rofecoxib is a member of a subgroup of nonsteroidal anti-inflammatory drugs (NSAIDs) known as cyclooxygenase-2 (COX-2)-selective inhibitors. It has been studied in adult and elderly patients in a number of painful conditions (primary dysmenorrhea, acute pain after dental and orthopedic surgery, osteoarthritis [OA], and rheumatoid arthritis). OBJECTIVE: This review discusses the clinical pharmacology of and clinical experience with rofecoxib, and the role of COX-2-selective inhibitors in clinical practice. METHODS: Pertinent studies were identified through searches of MEDLINE and EMBASE, as well as the Web sites and proceedings of relevant scientific meetings. RESULTS: Although the published literature is limited, the data indicate that rofecoxib is an effective analgesic agent for the painful conditions in which it has been studied. As a COX-2-selective inhibitor, rofecoxib offers safety advantages over traditional NSAIDs. In clinical trials, gastrointestinal (GI) toxicity, including mucosal damage, perforation, ulcers, and bleeding, occurred significantly less often in healthy volunteers and patients treated with rofecoxib than in those who received NSAIDs such as ibuprofen, naproxen, or diclofenac (all comparisons, P < 0.001). In terms of renal toxicity, rofecoxib does not appear to offer a safety advantage over traditional NSAIDs. Rofecoxib has not been shown to affect platelets (bleeding time and platelet aggregation), unlike traditional NSAIDs. CONCLUSIONS: Rofecoxib is an appropriate choice for patients who do not obtain adequate analgesia with acetaminophen and those who have not obtained adequate analgesia from, cannot tolerate, or are at risk for GI toxicity with traditional NSAIDs. Patients who require chronic analgesic medication (ie, those with OA), including those who take other medications daily for comorbid conditions, may also benefit from the once-daily dosing regimen of rofecoxib.