allopurinol

the xanthine oxidase inhibitor

The first-line urate-lowering therapy for gout and prophylaxis against tumour lysis syndrome.

• Mechanism: Inhibits Xanthine Oxidase, preventing conversion of Hypoxanthine $\to$ Xanthine $\to$ Uric Acid.

indications

1. Gout: Chronic management (Target Uric Acid $<360$ µmol/L).
   • Initiation: Start low (100 mg) to prevent flares. Cover with Colchicine/NSAID.
2. Tumour Lysis Syndrome: Prophylaxis in intermediate-risk patients. (Not effective for existing high uric acid - see Rasburicase).

dosing

• Renal Adjustment: Active metabolite (Oxypurinol) accumulates in renal failure.
• Standard: 100-300 mg daily. Max 800-900 mg.

adverse effects

• Allopurinol Hypersensitivity Syndrome (AHS/DRESS):
  • Risk: High mortality. Rash, Eosinophilia, Hepatitis, AKI.
  • Genetics: HLA-B*5801 (Han Chinese, Thai, Korean, African descent). Screening recommended in high-risk groups.
• Drug Interaction: Azathioprine / 6-MP.
  • Danger: Allopurinol blocks metabolism of Azathioprine $\to$ Fatal Bone Marrow Suppression.
  • Action: Reduce Azathioprine dose by 75% or switch urate agent.