Febuxostat: an alternative uric acid-lowering medicine for gout

The UK product information (Adenuric) states that febuxostat is indicated in adults for chronic hyperuricaemia in conditions where urate deposition has already occurred, including a history or presence of tophi or gouty arthritis. It is also indicated for prevention and treatment of hyperuricaemia in adults undergoing chemotherapy for blood cancers who are at intermediate to high risk of tumour lysis syndrome.

Uric acid is the end product of purine breakdown, produced through steps catalysed by xanthine oxidase. Febuxostat blocks that enzyme, which lowers uric acid production. It is a preventer: it is neither a painkiller nor a treatment for an attack.

For gout the recommended oral dose is 80mg once daily, with or without food. If serum uric acid is still above 6 mg/dL (357 micromol/L) after 2 to 4 weeks, a higher dose of 120mg once daily may be considered. The medicine acts quickly enough for serum uric acid to be rechecked after 2 weeks, with the aim of keeping it below 6 mg/dL.

Flare prophylaxis for at least 6 months is recommended. For tumour lysis syndrome the dose is started 2 days before cytotoxic therapy for a minimum of 7 days. No dose change is needed in older people or mild to moderate kidney impairment, though safety in severe renal impairment has not been fully evaluated.

Febuxostat should not be started until an acute attack has completely subsided. Flares may occur when treatment begins because changing uric acid levels can mobilise urate from tissue deposits. If a flare occurs during treatment it should not be discontinued; the flare is managed alongside, as appropriate for the individual.

Clinicians are advised to titrate febuxostat appropriately to minimise flares after starting. The flare protection, which is commonly an anti-inflammatory or colchicine, is one reason treatment is a long-term plan rather than a quick fix.

The product information says that in people with pre-existing major cardiovascular disease, such as previous heart attack, stroke or unstable angina, a higher rate of cardiovascular death was seen with febuxostat than with allopurinol in one post-authorisation study, while a later study did not show the same result. Treatment in people with pre-existing major cardiovascular disease should be undertaken cautiously and with regular monitoring.

People at risk of tumour lysis syndrome treated with febuxostat should be under cardiac monitoring as clinically appropriate.

Gout flares are listed among common effects, particularly early on. Headache, diarrhoea, nausea and rash occur, and uncommon effects include blurred vision, decreased libido and weight changes. Rare effects include blood count changes, anaphylaxis and drug hypersensitivity.

Serious allergic reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and anaphylaxis, have been reported rarely, and treatment must be stopped immediately if they are suspected. Somnolence, dizziness, paraesthesia and blurred vision have been reported, so take care before driving.

Using febuxostat with mercaptopurine or azathioprine is not recommended because inhibiting xanthine oxidase can raise their levels; if combined, their dose should be cut to 20 percent or less of the previous dose. It can be given with naproxen without dose changes. Interaction studies with other cytotoxic chemotherapy have not been conducted.

Data from a very limited number of exposed pregnancies did not show adverse effects, and animal studies do not indicate harm, but whether it enters breast milk is unknown, and a risk to a nursing infant cannot be excluded, so it should not be used while breastfeeding. Its effect on human fertility is unknown.