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- Title
Valdecoxib.
- Authors
Ormrod, D.; Wellington, K.; Wagstaff, A.J.
- Abstract
▴ In ten large, well-controlled, randomised trials (n = 203 to 1089), valdecoxib, a selective inhibitor of cyclo-oxygenase-2, was significantly more effective than placebo in the treatment of osteoarthritis, rheumatoid arthritis and pain associated with primary dysmenorrhoea, and for postsurgical analgesia. ▴ Valdecoxib 1.25 to 10mg twice daily and valdecoxib 10mg once daily were more effective than placebo for the relief of pain in patients with osteoarthritis of the knee, and dosages above 5mg twice daily were similar in efficacy to naproxen 500mg twice daily. Similarly, valdecoxib 5 and 10 mg/day were as effective for osteoarthritis of the hip as naproxen 500mg twice daily. ▴ In patients with rheumatoid arthritis, valdecoxib 10, 20 or 40 mg/day was significantly more effective than placebo, and similar in efficacy to naproxen 500mg twice daily; there were no significant differences in efficacy between the three dosages of valdecoxib. ▴ Valdecoxib 20 or 40mg administered 1 to 3 hours before and 12, 24 and 36 hours after hip arthroplasty provided significantly better analgesia than placebo, and significantly reduced the amount of morphine taken by patients. ▴ Single doses of valdecoxib 10 to 80mg administered before foot or oral surgery provided significantly better analgesia than placebo; when administered after oral surgery, valdecoxib 20 or 40mg provided greater sustained analgesia than oxycodone 10mg/paracetamol 1000mg or rofecoxib 50mg. ▴ In contrast to three nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), valdecoxib 40mg twice daily did not cause significant changes in platelet function and bleeding times. ▴ Chronic users of NSAIDs who were switched to valdecoxib 10 or 20 mg/day for 12 weeks experienced significantly fewer gastroduodenal erosions or ulcers than patients receiving ibuprofen 2400 mg/day or diclofenac 150 mg/day for 12 weeks. ▴ Valdecoxib was generally well tolerated in clinical trials, with a similar incidence of adverse events to placebo. Mild to moderate chronic pain caused by osteo- or rheumatoid arthritis is most often managed with nonsteroidal anti-inflammatory drugs (NSAIDs). These agents, often combined with opioids or local anaesthetics, are also used in the prevention and treatment of acute pain after surgery. NSAIDs share a common mode of action, namely inhibiting cyclo-oxygenase (COX) enzymes that are involved in the synthesis of prostaglandins. There are two isoforms of COX enzymes: the constitutively expressed COX-1 and the inducible COX-2. COX-1 is involved in prostaglandin synthesis in the gastric mucosa, platelets and kidneys, and inhibition of this enzyme by nonselective NSAIDs is thought to be responsible for the damage to the gastric mucosa and the antiplatelet activity associated with this class of drug. Furthermore, the inhibition of platelet function by nonselective NSAIDs increases the risk of bleeding in a peri-operative setting. In contrast, COX-2 is thought to primarily affect the generation of prostaglandins involved in inflammation. Thus, drugs that selectively inhibit COX-2 should suppress inflammation without causing the gastric adverse effects associated with the nonselective NSAIDs, or without increasing the risk of bleeding due to their lack of effects on platelet function. The launch of the first COX-2 inhibitors (celecoxib and rofecoxib) in 1999 provided the clinician with drugs that could be used to treat mild to moderate pain with reduced risk of gastric damage or antiplatelet activity. A new COX-2 inhibitor, valdecoxib, was recently approved in the US and is the subject of this review. An injectable prodrug of valdecoxib, parecoxib, has also been developed and reviewed previously in Drugs. Valdecoxib has been investigated for the treatment of chronic pain associated with osteoarthritis (OA), rheumatoid arthritis and pain associated with dysmenorrhoea, and for the prevention and suppression of acute postsurgical pain.
- Subjects
CYCLOOXYGENASE 2 inhibitors; ANALGESICS; PHARMACOKINETICS
- Publication
Drugs, 2002, Vol 62, Issue 14, p2059
- ISSN
0012-6667
- Publication type
Article
- DOI
10.2165/00003495-200262140-00005