Makindo Medical Notes

Related Subjects: | Hyperuricaemia | Acute and Chronic Gout | Allopurinol | Rasburicase

⚠️ Key safety warning: Allopurinol can cause Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), especially in individuals with the HLA-B*5801 allele (common in Han Chinese, Thai, and Korean patients). It has potentially lethal drug interactions with Azathioprine, Mercaptopurine, and Ciclosporin due to xanthine oxidase inhibition, causing accumulation of toxic metabolites. Always monitor FBC and LFTs and educate patients to report rashes immediately.

📘 About: Always check the BNF link here

• Allopurinol is a xanthine oxidase inhibitor used to reduce uric acid production in chronic gout and tumour lysis syndrome.
• Its active metabolite, oxypurinol (alloxanthine), accounts for the sustained urate-lowering effect.
• It is not an innocuous drug and should never be started for asymptomatic hyperuricaemia.

⚙️ Actions

• Inhibits conversion of xanthine → uric acid, lowering plasma urate concentration.
• By decreasing uric acid formation, it reduces urate crystal deposition and recurrence of gouty attacks.
• May take several weeks to achieve urate target (<360 μmol/L or <6 mg/dL).

🎯 Indications / Dosing (Check BNF)

• Chronic gout: Start at 100 mg daily; titrate by 100 mg every few weeks up to 300 mg daily (max 900 mg/day).
• Tumour lysis syndrome: 100–300 mg every 8 hours (often with hydration and alkalinisation of urine).
• Start ≥4 weeks after an acute gout attack to avoid exacerbation; use concurrent NSAID or colchicine prophylaxis for 1–3 months.
• Reduce dose in renal impairment — accumulation increases toxicity risk.

📊 Dose Range

🚫 Contraindications

• During acute gout attack (initiation only — continue if already established).
• Severe hepatic or renal impairment (unless specialist-adjusted).
• Known hypersensitivity to allopurinol or other xanthine oxidase inhibitors.

⚠️ Cautions

• Ensure adequate hydration to prevent renal uric acid crystallisation.
• Reduce dose in renal and hepatic dysfunction.
• Test for HLA-B*5801 in high-risk ethnic groups prior to initiation.

💊 Interactions

• Azathioprine / Mercaptopurine: Severe or fatal myelosuppression — reduce dose to ≤25% if co-administered (specialist only).
• Ciclosporin: Increased ciclosporin toxicity — monitor closely.
• Warfarin: Potentiates anticoagulant effect — monitor INR.
• ACE inhibitors / ARBs: Increased risk of leucopenia or hypersensitivity.
• Cyclophosphamide: May increase myelosuppression risk.

💥 Side Effects

• Skin reactions: Rash, pruritus — discontinue immediately if rash develops (risk of SJS/TEN).
• DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) — can be life-threatening.
• Hepatitis, eosinophilia, interstitial nephritis.
• Bone marrow suppression: leucopenia, thrombocytopenia.
• Gastrointestinal upset, metallic taste, headache, and rarely gynaecomastia.

🧠 Teaching Point

Allopurinol exemplifies the principle of enzyme inhibition therapy in metabolic disease. It reduces new uric acid formation but does not dissolve existing crystals — hence, gout may flare initially. The HLA-B*5801 association underscores how pharmacogenomics now guides safe prescribing. Clinicians must respect its powerful metabolic effects — lifesaving in tumour lysis, lethal in the wrong drug combination.

📚 References

• BNF: Allopurinol
• NICE CKS: Gout
• RCP National Guideline for the Management of Gout

🕓 Revisions

• 2025-10 — Reviewed and enhanced by Dr O’Kane (Makindo edition)