Celebrex (Searle)
100 mg and 200 mg capsules
Approved indication: arthritis
Australian Medicines Handbook Section 15.1
Non-steroidal anti-inflammatory drugs act by inhibiting the enzyme cyclo-oxygenase(COX).1 This enzyme is required for the synthesis of prostaglandins and its activity increases in inflammation. It has two isoforms, COX-1 andCOX-2, both of which are blocked to varying degrees by non-steroidal anti-inflammatory drugs. As COX-1 may produce protective prostaglandins in the stomach, its inhibition could be responsible for some of the adverse effects of the drugs. Celecoxib is much more selective for COX-2, so it may cause fewer adverse effects than the older drugs.
Patients with symptoms of rheumatoid arthritis take celecoxib in two divided doses. A single daily dose may be used in osteoarthritis. The drug is quickly absorbed. Although taking the capsules with food delays absorption, the bioavailability is increased. Celecoxib is metabolised in the liver by cytochrome P450 CYP2C9so there is a potential for interactions with drugs such as fluconazole.
In studies lasting up to 12 weeks, celecoxib has reduced the pain of osteoarthritis more effectively than placebo. Trials, of up to 24 weeks, in patients with rheumatoid arthritis have found the efficacy of celecoxib to be similar to that of naproxen 500 mg twice daily.
The effect of celecoxib on the gut has been assessed by endoscopy. Gastric ulcers were seen significantly less frequently during treatment with celecoxib, than they were in patients taking naproxen or diclofenac. Celecoxib, however, is not free of gastrointestinal adverse effects. Dyspepsia, abdominal pain and diarrhoea occur more frequently than with placebo. In animal studies, COX-2inhibitors retard ulcer healing.1
Most of the enzyme activity in platelets is COX-1, so celecoxib should have little effect on bleeding time. The potential of COX-2 inhibitors to cause fluid retention, renal impairment or hypertension is unknown. In clinical trials peripheral oedema occurred with equal frequency (2.1%) in patients taking celecoxib or naproxen. Celecoxib is not recommended for patients with aspirin-sensitive asthma.
The COX-2 inhibitors have the potential to replace non-steroidal anti-inflammatory drugs for the relief of arthritic symptoms. Whether or not they fulfill this potential will depend on their long-term safety. For example, will they cause fewer gastrointestinal haemorrhages than the non-steroidal anti-inflammatory drugs?
Reference
1. Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307-14.
