When would a patient diagnosed with hyperuricaemia who had been successfully managed with allopurinol be switched to febuxostat?
Allopurinol is a purine analogue and competitive inhibitor of xanthine oxidase, a key enzyme in the production of uric acid by purine metabolism. Thus, allopurinol can effectively reduce plasma urate levels in the management of hyperuricaemia and chronic gout. Febuxostat is a non-purine competitive inhibitor of xanthine oxidase recommended for people who cannot tolerate allopurinol.
Allopurinol is associated with increased risk of rare but potentially fatal serious cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Risk factors for allopurinol-induced SCAR include HLA-B5801 allele, starting dose of allopurinol, and renal impairment. The HLA-B5801 allele is more common among people of Asian ancestry, particularly the Han Chinese and Koreans. For example, in Singapore, the frequency of HLA-B*5801 prevalence is estimated at 18.5% (approximately 1 in 5 Singaporeans or 1 in 5 Chinese, 1 in 15 Malays, and 1 in 25 Indians).
Suppose a patient’s urate levels have responded well to allopurinol, but the patient has developed allopurinol-induced adverse effects, such as SCAR. In that case, switching to the other available xanthine oxidase inhibitor, febuxostat is a reasonable option.