Allopurinol
Zyloric · Allopurinol Sandoz
First-line urate-lowering treatment for gout, with the goal of titrating upward until serum urate is stably below 360 μmol/l — not setting a fixed dose and leaving it. Treatment is lifelong, and the first months require flare prophylaxis because falling urate levels themselves trigger attacks. Two features make this drug dangerous: the hypersensitivity syndrome and the combination with azathioprine.
Allopurinol blocks xanthine oxidase and thereby the breakdown of azathioprine and mercaptopurine — the combination causes life-threatening bone marrow suppression unless the thiopurine dose is reduced to 25 %. Allopurinol-induced hypersensitivity syndrome (DRESS) and Stevens–Johnson syndrome typically debut within the first two months and carry high mortality.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Gout, initiation | 100 mg orally daily, increase by 100 mg every 2–4 weeks | never initiate during an acute attack without prophylaxis |
| Gout, maintenance | titrate to serum urate < 360 μmol/l, usually 300–600 mg daily | target < 300 μmol/l in tophaceous gout |
| Flare prophylaxis at initiation | colchicine 0,5 mg 1–2 times daily for 3–6 months | alternatively NSAID or low-dose prednisolone |
| Urate nephropathy and recurrent urate stones | 300–600 mg orally daily | combine with alkalinisation and high fluid intake |
| Tumour lysis syndrome, prophylaxis | 100–300 mg daily from the day before cytotoxic therapy | rasburicase in high-risk cases |
The starting dose should be reduced in impaired renal function: 50–100 mg daily at eGFR 30–60 ml/min and 50 mg daily or every other day at eGFR < 30 ml/min. Titration toward the urate target may still proceed in renal impairment, but more slowly and with closer monitoring — the active metabolite oxipurinol accumulates.
Dose reduction in impaired hepatic function, with monitoring of liver tests during the first months.
Used in children primarily for tumour lysis syndrome and inborn errors of purine metabolism, 10–20 mg/kg/day, under specialist supervision. Gout is very rare in children.
Do not initiate allopurinol during an acute gout attack without concurrent flare prophylaxis — the rapid fall in urate mobilises crystals and worsens or prolongs the attack, and the patient will conclude that the drug does not work. Do not, however, discontinue ongoing treatment when an attack occurs.
Pharmacokinetics
- BIOAVAIL.
- 70–90 %
- t½ ALLOPURINOL
- 1–2 hours
- t½ OXIPURINOL
- 18–30 hours (prolonged in renal impairment)
- PROTEIN BINDING
- Negligible
- METABOLISM
- Xanthine oxidase to oxipurinol (active)
- EXCRETION
- Renal
- ONSET
- Urate reduction within 1–2 weeks, full effect after 2–4 weeks
- TARGET LEVEL
- Serum urate < 360 μmol/l, < 300 μmol/l in tophaceous gout