Hotline Archive - Rofecoxib (Vioxx)
July 1999
On May 21, 1999, the FDA approved the use of rofecoxib (Vioxx) for the relief of the signs and symptoms of osteoarthritis (OA), management of acute pain in adults, and treatment of menstrual pain. Rofecoxib is the second COX-2 inhibitor approved in the U.S. to date. Submission for an indication to treat rheumatoid arthritis (RA) has not occurred, although clinical trials are in progress.
In studies of patients with hip or knee OA, rofecoxib at 12.5 mg or 25 mg once daily was found to be superior to placebo and comparable to traditional NSAIDs -- including ibuprofen 800 mg t.i.d. or diclofenac 50 mg t.i.d. -- using outcomes such as pain, functional measures, and morning stiffness in studies lasting from six to 52 weeks. The analgesic effect of a single 50 mg dose of rofecoxib has further been shown to be comparable to a single dose of naproxen sodium 550 mg for relief of menstrual pain or ibuprofen 400 mg for relief of dental pain. In a pilot study in RA, at six weeks a greater percentage of patients taking rofecoxib showed improvement in signs and symptoms of RA than those taking placebo.
Rofecoxib has been shown to cause less GI blood loss and is associated with a lower rate of new ulcer formation than traditional NSAIDs. In one study of healthy volunteers, fecal blood loss was comparable in those treated with rofecoxib 25 mg or 50 mg q.d. and placebo, and less than that in those treated with ibuprofen 800 mg t.i.d. over a four-week period. In one trial, 1,516 patients with no prior ulcer history were randomized to receive rofecoxib 25 mg, 50 mg, placebo, or ibuprofen 800 mg t.i.d. Upper endoscopy at 12 weeks revealed comparable incidence of ulcers for placebo (7.3%), rofecoxib 25 mg q.d. (4.7%), or 50 mg q.d. (8.1%) - much lower than that seen in the group treated with ibuprofen (28.5%). At 24 weeks, the difference in cumulative ulcer incidence between rofecoxib 25 mg q.d. (9.7%), 50 mg q.d. (13.5%), and ibuprofen (46.7%) was even more striking. Whether longer term use will be associated with less gastrointestinal toxicity than traditional NSAIDs is not yet established.
The most common adverse effects associated with rofecoxib noted in clinical trials - URIs, diarrhea, nausea, and headache - have occurred with comparable frequency in those treated with traditional NSAIDs. Lower extremity edema (3.7%) and hypertension (3.5%) occurred at similar rates in those treated with rofecoxib and with traditional NSAIDs, which was higher than in those taking placebo. The higher 50 mg dose rofecoxib has been associated with a higher incidence of pedal edema (6.3%), hypertension (8.2%), and gastrointestinal symptoms. Rofecoxib taken with warfarin can cause a small (approximately 10%) increase in prothrombin time.
There are no data published in peer-reviewed journals comparing safety and efficacy of rofecoxib to celecoxib (Celebrex) or to acetaminophen. Unlike celecoxib, rofecoxib is a sulfone, not a sulfonamide, and should not cause reactions in patients allergic to sulfonamides. The wholesale price of rofecoxib 12.5 mg or 25 mg daily is roughly comparable to that of celecoxib 100 mg twice daily or 200 mg daily. Rofecoxib is also available as an oral solution (12.5 m g/5 ml).
July 13, 1999
Robert F. Spiera, MD
Editor, ACR Hotline
Hotline is provided by the ACR Communications and Marketing Committee as a service to members. This Hotline reflects the views of the author(s) and does not represent a position statement of the College.
