Allopurinol Dosing in Chronic Renal Failure
For patients with chronic renal failure (CRF), allopurinol should be started at 50 mg daily for stage 4 or worse CKD, with gradual titration upward every 2-5 weeks to achieve target serum uric acid levels. 1
Initial Dosing Based on Renal Function
- Normal to mild renal impairment: Start at 100 mg/day
- Stage 4 or worse CKD (creatinine clearance <30 ml/min): Start at 50 mg/day 1, 2
- Extreme renal impairment (creatinine clearance <10 ml/min): Daily dosage should not exceed 100 mg 2
- Very severe renal impairment (creatinine clearance <3 ml/min): Consider extending dosing interval 2
Dose Titration Protocol
- Begin with low dose as indicated above
- Increase dose by 100 mg increments every 2-5 weeks 1
- Monitor serum uric acid levels, targeting <6 mg/dL 1
- Continue upward titration until target is achieved or maximum tolerated dose is reached
Maximum Dosing Considerations
- Doses can be raised above 300 mg daily even with renal impairment 1
- This must be accompanied by:
- Adequate patient education
- Close monitoring for drug toxicity (pruritis, rash, elevated hepatic transaminases)
- Regular assessment of renal function
Monitoring Recommendations
- Serum uric acid levels every 2-5 weeks during titration
- Renal function (BUN, creatinine, creatinine clearance)
- Signs of hypersensitivity reactions (rash, fever, eosinophilia) 3
- Oxipurinol levels if available (target <15.2 μg/ml) 4
Important Precautions
- Consider HLA-B*5801 testing in high-risk populations (Koreans with stage 3 or worse CKD; Han Chinese and Thai patients) before initiating therapy 1, 3
- Maintain adequate hydration (2.5-3L fluid intake daily) 3
- Consider prophylaxis against acute attacks during initiation with colchicine (0.5-1 mg daily) and/or an NSAID with gastroprotection 1, 3
Rationale for Cautious Dosing
The need for reduced dosing in renal impairment is based on the pharmacokinetics of oxipurinol (the active metabolite of allopurinol), which has decreased clearance in renal dysfunction 4, 5. Studies have shown that oxipurinol clearance is directly proportional to creatinine clearance, and high oxipurinol levels are associated with increased risk of severe adverse reactions, including potentially life-threatening cutaneous reactions 5, 6.
Alternative Options for CRF Patients
If allopurinol is not tolerated:
- Febuxostat can be used without dose adjustment in moderate to severe renal impairment 3
- Benzbromarone can be considered for patients with mild to moderate renal insufficiency 1, 3
- Probenecid is not recommended in patients with creatinine clearance <50 ml/min 1
Despite the need for dose adjustment, appropriate allopurinol therapy in CRF patients may help preserve remaining kidney function, as some studies suggest it may slow the progression of renal disease 7, 8.