allopurinol
xanthine oxidase inhibitor· Brands: Zyloric, AloprimPO
Mechanism of action
Allopurinol inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid. This reduces uric acid production, lowering serum uric acid concentration and preventing urate crystal deposition in tissues.
Pharmacokinetics
Allopurinol is well absorbed after oral administration and is rapidly metabolised to its active metabolite, oxypurinol. Allopurinol has a half-life of about 1 to 2 hours, while oxypurinol's half-life is 18 to 30 hours, allowing once-daily dosing. Excretion is primarily renal, so dose adjustment is required in renal impairment.
Indications & dosing
Gout (prophylaxis and treatment)
Start 100 mg daily; titrate to target serum uric acid <360 micromol/L. Reduce dose in renal impairment.
- adult · PO: 100–600 mg OD · Start 100 mg daily; titrate to target serum uric acid <360 micromol/L. Reduce dose in renal impairment.
Tumour lysis syndrome (prevention)
Usually started 1-2 days before cytotoxic therapy; adjust based on uric acid and renal function.
- adult · PO: 200–300 mg OD · Usually started 1-2 days before cytotoxic therapy; adjust based on uric acid and renal function.
Uric acid nephrolithiasis
Dose adjusted to keep urine uric acid <600 mg/day; ensure adequate hydration.
- adult · PO: 100–300 mg OD · Dose adjusted to keep urine uric acid <600 mg/day; ensure adequate hydration.
Tumour lysis syndrome (prevention) in children
Maximum 400 mg/day. Adjust for renal impairment; monitor serum uric acid.
- pediatric · PO: 10–20 mg/kg OD · Maximum 400 mg/day. Adjust for renal impairment; monitor serum uric acid.
Contraindications & precautions
- Hypersensitivity to allopurinol or any of its excipients · A history of anaphylaxis or severe allergic reaction to allopurinol precludes its use.
- Acute gout attack · Do not initiate allopurinol during an acute attack; if already taking, continue. Starting may exacerbate or prolong the attack.
- Monitor serum uric acid and renal function regularly; adjust dose accordingly.
- Reduce dose in renal impairment and consider alternative if severe.
- If used with azathioprine or mercaptopurine, reduce the thiopurine dose by up to 75% (local protocols may vary).
- Do not initiate during an acute gout attack; continue if already established.
- Advise patient to stop the drug and seek immediate medical advice if a skin rash or other signs of hypersensitivity develop.
- Use caution in hepatic impairment; monitor liver function.
Adverse effects
- Skin rash
- Acute gout attack during initiation
- Nausea, vomiting, diarrhoea
- Stevens-Johnson syndrome / toxic epidermal necrolysisserious
- Hypersensitivity syndrome (DRESS)serious
- Blood dyscrasias (leucopenia, agranulocytosis, thrombocytopenia)serious
- Hepatic dysfunction or hepatitisserious
Interactions
- azathioprinemajorAvoid co-prescription. If unavoidable, reduce the azathioprine dose to approximately one quarter of the usual dose and monitor full blood count closely, especially during the first few weeks of therapy. Consider alternative agents or use of allopurinol with a different immunosuppressant.
Renal & hepatic adjustment
- eGFR 30–60: Reduce dose to 100 mg once daily; titrate according to serum urate levels.
- eGFR 10–30: Reduce dose to 50 mg once daily; use with caution.
- eGFR 0–10: Use with caution; consider 50 mg every other day.
Monitoring, pregnancy & toxicity
- Serum urate · Periodically, every 1 to 3 months during dose titration, then every 6 months.
- Renal function (serum creatinine / eGFR) · Before starting therapy and periodically during treatment.
- Liver function tests · At baseline and periodically, especially in hepatic impairment or if symptoms develop.
- Skin for rash (hypersensitivity) · Monitor for any skin reactions; advise patients to seek immediate medical attention if rash develops.
- Full blood count · If blood dyscrasias are suspected.
- Pregnancy: Allopurinol is not recommended during pregnancy unless clearly necessary, as there is limited human data. It should be used only if the potential benefit to the mother outweighs the potential risk to the fetus.
- Toxicity: Overdose may cause gastrointestinal symptoms (nausea, vomiting, diarrhoea), rash, and flu-like illness. Severe cases may cause hepatotoxicity or nephrotoxicity. · Discontinue allopurinol and provide supportive care; monitor renal and hepatic function. Consider activated charcoal if ingestion is within 1 hour.
Clinical notes
Allopurinol is used for hyperuricaemia associated with gout, uric acid stones, and tumour lysis syndrome. Initiate at a low dose and titrate to achieve target urate levels. Common adverse effects include rash and gastrointestinal upset; serious hypersensitivity reactions can occur. In patients with renal impairment, reduce dose. Consider HLA-B*5801 screening in high-risk populations. Do not start during an acute attack; continue during attack if already taking. Avoid in pregnancy unless clearly necessary.
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BNF; local formulary