see also gout

• Originally synthesised as candidate for antineoplastic activity which it lacked but proved to be a substrate for & inhibitor of xanthine oxidase thus reducing uric acid production although it also inhibits uric acid renal excretion;
• Normally uric acid is the sole urinary purine, but in with allopurinol, purines are excreted in urine as hypoxanthine & xanthine as well which are more soluble;
• The lowered [uric acid]serum below its limit of solubility facilitates the dissolution of tophi & prevents development or progression of chronic gouty arthritis as well as preventing formation of uric acid stones & thus prevents nephropathy assoc. with gout;
• usually start at 200mg/d and gradually increase to 600mg/d.

• Well tolerated by most patients, most commonly HS reactions even after yrs Rx !;
• May induce incr. freq. ac. gout attacks initial months of Rx
  • → cover with colchicine or non-steroidal anti-inflammatory drugs (NSAIDs);
  • → don't start allopurinol within 6wks of an acute attack
• Xanthine stones in kidney uncommon but esp. high uric acid producers → increase fluid intake to prevent;
  • see urolithiasis
• Headache, drowsiness, N/V/D/gastric irrit., vertigo occas. but cont. Rx ;
• Pruritic rash, fever, malaise, myalgia in 3% but more likely if decr. renal function;

• PH serious side effect; lactation; children (unless malig./inborn errors);
• Idiopathic haemochromatosis & their immed. relatives; 1st sign drug rash;

• impaired renal/hepatic function ⇒ risk of fatal exfoliative syndrome 1-6wk after starting Rx:
  • exfoliative rash
  • fever
  • hepatitis
  • renal failure
  • NB. this syndrome is more likely if pre-existing renal insufficiency or concomitant diuretics

• Azathioprine → decr. metab. azathioprine → decr. dose by 33%;
• Mercaptopurine → decr. metab. mercaptopurine → decr. dose by 25%;
• warfarin → decr. metab. warfarin → monitor INR carefully;
• Theophylline → decr. theoph. clearance → monitor [] & ? decr. dose;
• Thiazides → incr. serum [uric acid] → may need incr. allopurinol dose;
• Fe suppl. →