Etoricoxib

Arcoxia (Merck Sharp & Dohme)
30 mg, 60 mg and 120 mg tablets
Approved indications: analgesia, gout, osteoarthritis
Australian Medicines Handbook section 15.1.1

Etoricoxib is a non-steroidal anti-inflammatory drug which mainly inhibits the cyclo-oxygenase-2 enzyme (see 'COX-2 inhibitors', Aust Prescr 2000;23:30-2). By reducing the synthesis of inflammatory mediators, etoricoxib can modify the pain response.

Acute gout presents with pain and inflammation. Etoricoxib has therefore been studied in the early treatment of acute gout in a double-blind trial involving 150 patients. The patients were randomised to take indomethacin 50 mg three times a day or a once-daily dose of etoricoxib 120 mg for eight days. Both drugs reduced pain and swelling with no significant differences in efficacy. Overall, there was no significant difference in adverse events, but etoricoxib caused fewer drug-related adverse effects.¹

Etoricoxib is also approved for use in primary dysmenorrhoea and postoperative dental pain. A single dose of 120 mg provides similar analgesia to ibuprofen 400 mg and naproxen 550 mg.

The early studies of etoricoxib in osteoarthritis used a dose of 60 mg daily. This dose was found to have the maximum efficacy in a six-week dose-ranging trial involving 617 patients with osteoarthritis of the knee.² In a 12-week study of 501 patients with osteoarthritis of the hip or knee, etoricoxib 60 mg reduced pain significantly more than placebo. Its efficacy was similar to that of naproxen 500 mg twice daily.³

Two longer-term studies also compared etoricoxib 60 mg daily with naproxen 500 mg twice daily. Almost 1000 patients were randomised to take etoricoxib, naproxen or a placebo for 12 weeks. This was followed by a 40-week comparison of etoricoxib and naproxen and then an 86-week extension study. The active drugs were significantly better than placebo in the first 12 weeks. After 52 weeks there was no significant difference between etoricoxib and naproxen. The reduction in pain was maintained over the whole 138 weeks of the studies.⁴

Following the withdrawal of rofecoxib in 2004, there has been increased concern about the adverse effects of COX-2 inhibitors. Although 60 mg is a more effective dose2, the recommended dose of etoricoxib for osteoarthritis has been reduced to 30 mg daily. This dose was used in a trial which compared the drug with placebo or ibuprofen 800 mg three times daily for 12 weeks. The 528 patients in the study had osteoarthritis of the knee or hip. The active drugs had comparable efficacy, but were significantly better than placebo. Most of the benefit was achieved by the second week of treatment.⁵

Although COX-2 inhibitors were expected to have fewer serious gastrointestinal complications than other non-steroidal anti-inflammatory drugs, abdominal pain can be a reason for people stopping treatment with etoricoxib. After 40 weeks of treatment, 8.5% of the patients discontinued etoricoxib 60 mg because of drug-related adverse events (11.4% of the naproxen group discontinued). Common adverse effects included dyspepsia, epigastric discomfort, heartburn and hypertension.⁴ In the study of etorixocib 30 mg, only 3.3% of the patients discontinued because of drug-related adverse events, compared with 9% of the ibuprofen group.⁵

Data from long-term comparisons of etoricoxib and diclofenac have been used to investigate cardiovascular and gastrointestinal safety. These studies involved more than 34 000 patients over the age of 50 years with rheumatoid arthritis or osteoarthritis. They took diclofenac 75 mg twice daily or 50 mg three times a day, or etoricoxib 60 mg or 90 mg daily. The mean duration of treatment was approximately 18 months. Thrombotic events, such as myocardial infarction and stroke, affected 468 of the patients taking diclofenac and 495 of those taking etoricoxib. This difference is not statistically significant.⁶ Upper gastrointestinal events occurred in 246 patients taking diclofenac and in 176 taking etoricoxib. This statistically significant advantage for etoricoxib was mainly accounted for by uncomplicated ulcers. Etoricoxib did not significantly reduce the rate of complications such as perforation and bleeding.⁷

Active peptic ulceration is a contraindication to etoricoxib as are vascular disease, heart failure and uncontrolled hypertension. Treatment should be stopped if hepatic dysfunction develops.

Etoricoxib is well absorbed and does not have to be taken with food. It is almost completely metabolised with most of the metabolites appearing in the urine. The long half-life enables once-daily dosing. Etoricoxib is contraindicated in patients with severe renal or hepatic impairment.

Caution is also advised if etoricoxib is considered for patients who are also taking drugs that are known to potentially interact with non-steroidal anti-inflammatory drugs. These drugs include ACE inhibitors, diuretics, oestrogens and lithium. Etoricoxib may also increase the effect of warfarin.

If etoricoxib is used for acute pain the daily dose should not exceed 120 mg. This can only be used for a maximum of eight days.

Australian guidelines do not support long-term use of non-steroidal anti-inflammatory drugs or COX-2 inhibitors in osteoarthritis. Etoricoxib should be used at the lowest dose for the shortest possible time. If a patient's arthritic pain does not improve within a few weeks, the drug should be stopped. Although etoricoxib has been studied in rheumatoid arthritis, it is not approved for this condition.

manufacturer provided the product information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

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.