Etoricoxib: a COX-2 inhibitor for arthritis and acute gout

According to the UK product information, etoricoxib is indicated in adults and adolescents aged 16 and over for symptomatic relief of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, and for the pain and signs of inflammation associated with acute gouty arthritis. It is also licensed for short-term treatment of moderate pain after dental surgery.

It is a selective cyclo-oxygenase-2 inhibitor. COX-2 is the enzyme form associated with pain, inflammation and fever, and etoricoxib reduces it without inhibiting COX-1 or affecting platelet function at normal doses. That is why it does not replace aspirin when aspirin has been prescribed to prevent blood clots.

The product information stresses using the shortest duration and lowest effective daily dose, and reviewing the need for it periodically, particularly in osteoarthritis, because cardiovascular risks may rise with dose and duration. Doses differ by condition, and the information states ceilings for each, which a prescriber applies. Some doses are deliberately short: acute gout treatment is limited to a maximum of 8 days, and dental surgery pain to 3 days.

It is taken by mouth with or without food. Onset may be faster when taken without food, which can matter when quick relief is wanted. People with mild or moderate liver impairment are given lower maximum doses, and it is contraindicated in severe liver impairment.

The contraindications include allergy to the active substance, active stomach ulcer or gut bleeding, breathing or allergic-type reactions after aspirin or other NSAIDs, pregnancy and breastfeeding, severe liver impairment, kidney function below the stated threshold, under-16s, inflammatory bowel disease, congestive heart failure (NYHA II-IV), persistently high blood pressure above 140/90 mmHg that is not adequately controlled, and established ischaemic heart disease, peripheral arterial disease or cerebrovascular disease.

Because of the blood pressure and circulation points, prescribers normally check blood pressure and cardiovascular risk factors such as high cholesterol, diabetes and smoking before choosing a COX-2 inhibitor.

Like other NSAIDs it can cause stomach and gut problems, including ulcers and bleeding, raised blood pressure, fluid retention and swelling, dizziness and headache. Serious reactions reported include heart attack and stroke, heart failure, severe skin and allergic reactions including angioedema and anaphylaxis, and liver and kidney effects.

Seek urgent help for chest pain, breathlessness, weakness on one side or slurred speech, black stools or vomiting blood, swelling of the face or throat, or yellowing of the skin. Anyone who gets dizziness, vertigo or sleepiness should not drive or operate machinery.

There are no clinical data on exposed pregnancies, and animal studies have shown reproductive toxicity, so it is contraindicated in pregnancy. Like other prostaglandin-inhibiting drugs it may affect the baby's kidneys later in pregnancy. Women must not breastfeed while using it, because it is excreted in the milk of lactating rats and effects in humans are unknown.

Use of any COX-2 inhibitor is not recommended in women attempting to conceive.

Warfarin and other anticoagulants need monitoring because prothrombin time (INR) can rise. NSAIDs may reduce the effect of diuretics, ACE inhibitors and angiotensin II blockers, and the risk of kidney problems is higher in dehydrated or older people. Ciclosporin and tacrolimus may have increased kidney toxicity with NSAIDs, and lithium levels can rise, so blood lithium is monitored closely.

Weekly methotrexate interactions are described and warrant monitoring. Etoricoxib can increase ethinylestradiol levels in some oral contraceptives and in hormone replacement therapy, which a prescriber will weigh. It can be used with low-dose aspirin, though the stomach risk is higher. Using another non-aspirin NSAID at the same time is generally avoided.