Introduction

Allopurinol is used in the prevention of gout.

Mechanism of action

It works by inhibiting xanthine oxidase.

Indications

Initiating allopurinol prophylaxis - see indications below
  • 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 ┬Ámol/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'
  • tophi
  • renal disease
  • uric acid renal stones
  • prophylaxis if on cytotoxics or diuretics

*patients with Lesch-Nyhan syndrome often take allopurinol for life

Adverse effects

The most significant adverse effects are dermatological and patients should be warned to stop allopurinol immediately if they develop a rash:
  • 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.

Contraindications

Interactions

Azathioprine
  • 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

Cyclophosphamide
  • allopurinol reduces renal clearance, therefore may cause marrow toxicity

Theophylline
  • allopurinol causes an increase in plasma concentration of theophylline by inhibiting its breakdown