Allopurinol

Common indications

• To prevent acute attacks of gout. 
• To prevent uric acid and calcium oxalate renal stones. 
• To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy.

 

Physiology

• Xanthine oxidase metabolises xanthine (produced from purines) to uric acid.

 

Mechanisms of action

• Allopurinol is a xanthine oxidase inhibitor.
• Inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys.

 

Important adverse effects

• Allopurinol is generally well tolerated. 
• The most common side effect is a skin rash, which may be mild or may indicate a more serious hypersensitivity reaction such as Stevens–Johnson syndrome or toxic epidermal necrolysis. 
• Drug hypersensitivity syndrome is a rare, life-threatening reaction to allopurinol that can include fever, eosinophilia, lymphadenopathy and involvement of other organs, such as the liver and skin. 
• Starting allopurinol can trigger or worsen an acute attack of gout.

 

Warnings

• Allopurinol should not be started during acute attacks of gout, but can be continued if a patient is already established on it, to avoid sudden fluctuations in serum uric acid levels.  
• Recurrent skin rash or signs of more severe hypersensitivity to allopurinol are contraindications to therapy. 
• Allopurinol is metabolised in the liver and excreted by the kidney. The dose should therefore be reduced in patients with severe renal impairment or hepatic impairment.