Timing of Allopurinol Administration
Allopurinol can be taken once daily at any time of day—morning or night—as a single dose provides sustained uric acid control equivalent to divided dosing. 1
Evidence for Once-Daily Dosing
A controlled study in gout patients demonstrated that allopurinol 300 mg given as a single morning dose achieved the same sustained control of plasma uric acid levels as divided administration (100 mg three times daily). 1
The pharmacokinetics of allopurinol support once-daily dosing: the parent drug has a short half-life of approximately 1.2 hours, but its active metabolite oxypurinol has a much longer elimination half-life of 23.3 hours, providing sustained xanthine oxidase inhibition throughout the day. 2
Oxypurinol accumulates during long-term administration and is responsible for the majority of allopurinol's hypouricemic efficacy, making the timing of the daily dose clinically irrelevant. 2, 3
Practical Dosing Recommendations
Start at 100 mg daily (or lower in patients with chronic kidney disease) and titrate upward by 100 mg increments every 2-4 weeks until target serum uric acid <6 mg/dL is achieved. 4, 5
The maximum FDA-approved dose is 800 mg/day, though doses above 300 mg/day are often required to reach therapeutic targets. 5
For pediatric patients with tumor lysis syndrome prophylaxis, allopurinol is dosed every 8 hours (50-100 mg/m² per dose), but this reflects a different clinical context requiring more intensive monitoring. 4
Key Clinical Considerations
Always provide anti-inflammatory prophylaxis (colchicine 0.5-1 mg/day, NSAIDs, or low-dose corticosteroids) when initiating allopurinol to prevent paradoxical gout flares during the first 6 months of therapy. 4, 5, 6
Patient adherence may improve with once-daily dosing compared to multiple daily doses, and plasma oxypurinol monitoring can help identify non-adherent patients. 2
In renal impairment, reduce the starting dose but oxypurinol accumulation means the timing of administration remains flexible—focus on appropriate dose adjustment rather than timing. 2, 3