Allopurinol in chronic gout

Allopurinol is the most widely prescribed drug for gout prophylaxis in the UK.

• allopurinol is the recommended first-line ULT (urate lowering therapy) to consider. It should be started at a low dose (50-100 mg daily) and the dose then increased in 100 mg increments approximately every 4 weeks until the sUA (serum uric acid) target has been achieved (maximum dose 900 mg)
  • in patients with renal impairment, smaller increments (50 mg) should be used and the maximum dose will be lower, but target urate levels should be the same
• febuxostat can be used as an alternative second-line xanthine oxidase inhibitor for patients in whom allopurinol is not tolerated or whose renal impairment prevents allopurinol dose escalation sufficient to achieve the therapeutic target
  • start with a dose of 80 mg daily and, if necessary, increase after 4 weeks to 120 mg daily, to achieve therapeutic target
• colchicine 0.5mg bd or od should be considered as prophylaxis against acute attacks resulting from initiation or up-titration of any ULT and continued for up to 6 months
  • in patients who cannot tolerate colchicine, a low-dose NSAID or coxib, with gastroprotection, can be used as an alternative providing there are no contraindications

Notes:

• initiation of prophylactic therapy may provoke an acute gout attack and so an NSAID or colchicine should be given concomitantly for at least the first 3 months
  • regarding colchicine:
    • there is evidence that patients starting allopurinol for crystal-proven chronic gouty arthritis while receiving colchicine 0.6 mg po bd reduces the frequency and severity of acute flares, and reduces the likelihood of recurrent flares. Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported (2)
• prophylactic therapy should not be started during an acute attack because it can prolong symptoms
• if an acute attack occurs during prophylactic treatment, this should be continued at the same dose while the acute attack is treated with an NSAID or colchicine
• maximum dose of allopurinol (3)
  • maximum dose of allopurinol in the UK is 900 mg daily. However, the maximum permitted dose of allopurinol is lower in the presence of impaired renal function, determined by the degree of impairment. In severe renal failure, allopurinol should be commenced at the lower dose of 50 mg daily and increased in 50 mg increments. ULT is usually considered to be lifelong. Serum urate levels should be checked annually once target levels have been achieved
• comparing allopurinol and febuxostat (4):
  • allopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease

The summary of product characteristics must be consulted before prescribing this drug.

Reference:

1. Hui M et al. for the British Society for Rheumatology Standards, Audit and Guidelines Working Group, The British Society for Rheumatology Guideline for the Management of Gout, Rheumatology (2017), 56 (7): 1056-1059, https://doi.org/10.1093/rheumatology/kex150
2. Borstad GC et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J. Rhuematol 2004;31:2429-32.
3. Arthritis Research UK (2011). Hands On (9) - gout: presentation and management in primary care.
4. O'Dell JR et al.Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management NEJM Evid 2022; 1 (3) DOI:https://doi.org/10.1056/EVIDoa2100028