Allopurinol Indications
Allopurinol is primarily indicated for the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy), management of patients with cancer-related hyperuricemia, and management of patients with recurrent calcium oxalate calculi with excessive daily uric acid excretion. 1
Primary Indications
- Allopurinol is indicated for patients with recurrent acute gout attacks, arthropathy, tophi, or radiographic changes of gout 2
- It is used in the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels 1
- Allopurinol is indicated for patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients 1
Important Considerations for Use
- Allopurinol is not recommended for the treatment of asymptomatic hyperuricemia 1
- Treatment should be discontinued when the potential for overproduction of uric acid is no longer present (in cases of cancer therapy) 1
- Therapy should be carefully assessed initially and reassessed periodically to determine that treatment benefits outweigh risks 1
Therapeutic Goals and Dosing
- The therapeutic goal of allopurinol therapy is to maintain serum uric acid below 6 mg/dL (360 μmol/L) to promote crystal dissolution and prevent crystal formation 2
- For patients with severe gout (tophi, chronic arthropathy, frequent attacks), a lower target of <5 mg/dL (300 μmol/L) is recommended until total crystal dissolution occurs 2
- Allopurinol should be started at a low dose (100 mg daily or less in patients with renal insufficiency) and gradually increased by 100 mg every 2-4 weeks until the target serum uric acid level is reached 2
- Doses above 300 mg daily are often necessary to achieve target urate levels, with doses up to 800 mg daily approved by the FDA 3, 4
Special Populations
- In patients with renal impairment, allopurinol should be started at a lower dose (50-100 mg daily) and titrated cautiously 5, 3
- The American College of Rheumatology recommends allopurinol as the preferred first-line agent for all patients with gout, including those with moderate to severe chronic kidney disease (stage ≥3) 3
Monitoring and Follow-up
- Regular monitoring of serum urate (every 2–5 weeks) during dose titration is recommended 2
- Once the target serum urate is achieved, monitoring should continue every 6 months to ensure maintenance of target levels and assess adherence 6, 3
- Monitor for adverse effects, particularly hypersensitivity reactions, which can include rash, pruritis, elevated hepatic transaminases, and eosinophilia 2
Prophylaxis During Initiation
- Concomitant anti-inflammatory prophylaxis (colchicine 0.5-1 mg daily and/or an NSAID with gastric protection) is strongly recommended during the first months of allopurinol therapy to prevent acute gout flares 2, 3
- Prophylaxis should typically be continued for 3-6 months 3
Common Pitfalls to Avoid
- Discontinuing allopurinol after achieving symptom control is a significant error that leads to recurrence of gout attacks in approximately 87% of patients within 5 years 6, 3
- Relying solely on the standard 300 mg dose, which fails to achieve target urate levels in more than half of gout patients 2, 4
- Underestimating the need for lifelong therapy based on temporary symptomatic improvement 6, 5
Allopurinol remains the first-line urate-lowering therapy for gout due to its efficacy, safety profile, and cost-effectiveness 3, 7. When properly dosed and monitored, it effectively reduces serum uric acid levels and prevents the long-term complications of gout.