Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Vioxx (Merck Sharp & Dohme)
12.5 mg and 25 mg tablets
Approved indication: osteoarthritis
Australian Medicines Handbook Section 15.1
Rofecoxib is the second inhibitor of cyclo-oxygenase 2 (COX-2) to be marketed in Australia. Unlike celecoxib (see 'New drugs' Aust Prescr 1999;22:147-8), in Australia its approval is limited to osteoarthritis.
Compared to celecoxib, rofecoxib is more selective for COX-2. It therefore has little effect on the synthesis of prostaglandins in the gut. Rofecoxib has a half-life of 17 hours and can be taken once a day. Each dose is well absorbed resulting in a bioavailability of 93%. The drug is metabolised in the liver and most of the metabolites are excreted in the urine.
In clinical trials rofecoxib has reduced joint pain in osteoarthritis more than placebo. It also improves stiffness and joint function. During a six-week study the efficacy of 12.5 mg or 25 mg rofecoxib daily was similar to that of 800 mg ibuprofen three times a day. In a year-long comparison, rofecoxib was comparable to 50 mg diclofenac three times a day.
Studies which used endoscopy to look for gastroduodenal ulcers, found that rofecoxib 25 mg or 50 mg/day caused significantly fewer ulcers than ibuprofen2400 mg/day during 24 weeks of treatment. However, gastrointestinal bleeding can still occur. Among the 3357 patients treated with rofecoxib in clinical trials, three experienced a haemorrhage. This incidence is lower than that seen with non-steroidal anti-inflammatory drugs, but a long-term study of comparative safety has not been performed.
In the clinical trials of rofecoxib the most commonly reported adverse effects were headache, diarrhoea and abdominal pain. Some patients will have increased blood pressure or fluid retention so extra caution is required if a patient has heart failure or reduced renal function. Approximately 1% of patients will develop abnormal liver function tests. Rofecoxib interacts with several drugs including warfarin and ACE inhibitors.
For patients with osteoarthritis, who cannot be managed with other analgesics, prescribers now have a choice between celecoxib and rofecoxib. Although rofecoxib is more selective it may not be safer. Until evidence of long-term safety and efficacy is available the choice of treatment will be influenced by the cost of the drugs.
