• Start allopurinol after two or more attacks of gout within a year or after the first attack in people who are at higher risk with one or more tophi, X-ray features of gouty arthritis, renal impairment, uric acid stones, or on long-term diuretic medication:
• Start allopurinol 1–2 weeks after the inflammation has settled and titrate the dose every few weeks until the serum uric acid (SUA) level is below 300 micromol/L.
• Co-prescribe a low dose of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose colchicine for a minimum of 6 weeks, to prevent acute attacks of gout when starting allopurinol. Consider the need for gastroprotective medication when prescribing an NSAID.
• If NSAIDs and colchicine are contraindicated or not tolerated, low-dose oral prednisolone once a day for 4 to 12 weeks is recommended.
• Consider febuxostat as second-line therapy if allopurinol is not tolerated or contraindicated. The dose may be increased after 2–4 weeks if the SUA level remains above 360 micromol/L.
• Co-prescribe a low dose of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose colchicine for at least 6 months, to prevent acute attacks of gout when starting febuxostat. Consider the need for gastroprotective medication when prescribing an NSAID.
• If NSAIDs and colchicine are contraindicated or not tolerated, low-dose oral prednisolone once a day for 4 to 12 weeks is recommended.

• It is important to explain that urate-lowering medication is normally lifelong and regular monitoring is needed.
• Advise the person that allopurinol or febuxostat may cause acute attacks of gout just after initiating treatment, and for some weeks afterwards. Explain that they should start their anti-inflammatory treatment as soon as possible and not to stop their allopurinol or febuxostat during acute attacks.

The recommendations regarding allopurinol are based on published expert opinion, pragmatic advice and a guideline produced by expert representatives of the British Society for Rheumatology (BSR). The evidence supporting the BSR recommendations is based on a systematic review of literature [Jordan et al, 2007]. The quality of the evidence on allopurinol is poor and CKS could not find any prospective randomized controlled trials (RCTs) comparing different agents.

The recommendations regarding febuxostat are based on a NICE technology appraisal Febuxostat for the management of hyperuricaemia in people with gout [NICE, 2008], and the Summary of Product Characteristics [ABPI Medicines Compendium, 2010].

• In the UK, allopurinol is the first-line urate-lowering drug recommended. Probenecid, sulfinpyrazone, or benzbromarone are not commonly used and have limitations to their use.
• Starting a urate-lowering drug is usually recommended after a second attack of gout in a year, as 40% of people will not experience another attack within the first year and lifestyle modifications can be effective. People with very high serum uric acid levels, renal impairment, previous uric acid stones, visible tophi, or on diuretic medication may be vulnerable to repeated attacks of gout and end organ damage (kidneys and joints), so treatment may be advisable after the first attack [Jordan et al, 2007].
• Urate-lowering drugs: the evidence suggests that use of a urate-lowering drug is effective at reducing recurrent acute attacks of gout. Clinical observation suggests that starting prophylactic treatment too early after an attack (before 1–2 weeks after the inflammation has settled) can lead to a prolonged flare up of gout.
• Evidence for using nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine: there is no evidence base for prophylactic low-dose NSAIDs, although these are routinely used in practice. One small RCT (n = 43) showed that colchicine (0.6 mg) twice daily for 6 months reduced the number of flares when starting allopurinol, compared with placebo (at least one flare occurred in 33% of the colchicine group compared with 77% of the placebo group, NNT = 3) [Borstad et al, 2004].
• Evidence for duration of NSAIDs or colchicine: it is recommended to co-prescribe a low-dose NSAID or colchicine for a minimum of 6 weeks when starting allopurinol, although this may be necessary for up to 6 months. The British National Formulary recommends gout flare prophylaxis for 3 months [BNF 53, 2007]. The Summary of Product Characteristics for febuxostat recommends gout flare prophylaxis for at least 6 months [ABPI Medicines Compendium, 2010].
• Oral prednisolone: if the use of NSAIDs and colchicine are contraindicated, the recommendation to use oral prednisolone for up to 3 months is based on the professional opinion of expert reviewers.