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allopurinol

allopurinol

see also gout

Summary

  • 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.

Common Adverse Effects:

  • Well tolerated by most patients, most commonly HS reactions even after yrs Rx !;
  • May induce incr. freq. ac. gout attacks initial months of Rx
  • Xanthine stones in kidney uncommon but esp. high uric acid producers → increase fluid intake to prevent;
  • 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;

C/I:

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

Specific precautions

  • 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

Drug Interactions:

  • 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. →
allopurinol.txt · Last modified: 2011/08/25 21:23 (external edit)