Mechanism of action
- allopurinol should not be started until 2 weeks after an acute attack has settled
- initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of < 300 µmol/l
- NSAID or colchicine cover should be used when starting allopurinol
Indications for allopurinol*
- recurrent attacks - the British Society for Rheumatology recommend 'In uncomplicated gout uric acid lowering drug therapy should be started if a second attack, or further attacks occur within 1 year'
- renal disease
- uric acid renal stones
- prophylaxis if on cytotoxics or diuretics
*patients with Lesch-Nyhan syndrome often take allopurinol for life
- severe cutaneous adverse reaction (SCAR)
- drug reaction with eosinophilia and systemic symptoms (DRESS)
- Stevens-Johnson syndrome
Certain ethnic groups such as the Chinese, Korean and Thai people seem to be at an increased risk of these dermatological reactions.
Patients at a high risk of severe cutaneous adverse reaction should be screened for the HLA-B *5801 allele.
- metabolised to active compound 6-mercaptopurine
- xanthine oxidase is responsible for the oxidation of 6-mercaptopurine to 6-thiouric acid
- allopurinol can therefore lead to high levels of 6-mercaptopurine
- a much reduced dose (e.g. 25%) must therefore be used if the combination cannot be avoided
- allopurinol reduces renal clearance, therefore may cause marrow toxicity
- allopurinol causes an increase in plasma concentration of theophylline by inhibiting its breakdown