A second COX-2 inhibitor

In July, the Food and Drug Administration approved Merck’s Vioxx (rofecoxib), which will join Pfizer’s Celebrex (celecoxib) as the second selective cyclooxygenase type 2 (COX-2) inhibitor on the market within the new class of nonsteroidal anti-inflammatory drugs (NSAIDs) available for the treatment of osteoarthritis (OA). Celebrex was approved in December 1998.

Rofecoxib’s approval indicates use for OA, the management of acute pain, and for the treatment of dysmenorrhea. The label indications for celecoxib are for the management of OA and rheumatoid arthritis. Merck’s ability to obtain labeling information for acute pain is timely and potentially advantageous, based on the newly recognized shift in OA treatment from decreased inflammation to simple pain relief (see cover story).

Joseph Golbus, MD, however, head of the division of rheumatology at Evanston (IL) Northwestern Healthcare, says both drugs achieve the desired effect of pain relief without the gastrointestinal (GI) side effects of the widely used first-generation NSAIDs.

The COX-2 inhibitors breakthrough came when researchers found two forms of the cyclooxygenase enzyme that NSAIDs are used to block. The COX-1 enzyme protects the stomach lining, while the COX-2 enzyme causes inflammation.

Traditional NSAIDs block both enzymes, making the body vulnerable to GI toxicity that can result in bleeding and ulcers. The selective COX-2 drugs attack only the inflammatory enzyme, leaving the COX-1 enzyme to protect the stomach lining. Both COX-2 inhibitors are recommended at a dose of between 12.5 mg and 25 mg once daily.

In clinical trials of celecoxib, the recommended dosage proved similar in efficacy to 800 mg of ibuprofen or 50 mg of diclofenac.

In terms of the decreased toxicity of the COX-2 inhibitors, trials of rofecoxib as high as 50 mg daily were associated with lower rates of ulcers than the standard dosage of 2,400 mg of ibuprofen daily. Approval of rofecoxib followed trials of approximately 3,300 patients.

Interaction cautions include its use with rifampin, methotrexate, and warfarin. Like celecoxib, rofecoxib’s label will carry a warning concerning GI ulcers and bleeding, though few cases were documented during trials.

The drug is expected to be on the shelves by this fall, supplied as 12.5 mg and 25 mg tablets in bottles of 30, 100, 1,000, and 8,000, and in an oral suspension at 12.5 mg or 25 mg per 5 mL. The drug is expected to be priced at $2.02 per tablet and $3 per 5 mL suspension.

[For more on rofecoxib, contact Merck in West Point, PA, at (800) 672-6372. For more on celecoxib, contact Pfizer in New York City at (800) 438-1985 and see the July 1999 issue of Drug Utilization Review.]