Can Hydroxyurea Cause or Worsen Gout?
Yes, hydroxyurea can cause hyperuricemia and potentially trigger or worsen gout through temporary impairment of renal tubular function, leading to elevations in serum uric acid levels. 1
Mechanism of Hyperuricemia
Hydroxyurea causes temporary impairment of renal tubular function that is accompanied by elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine. 1 This mechanism directly increases the risk of hyperuricemia, which can precipitate gout attacks or worsen existing gout.
Clinical Evidence and Management
Drug Interaction Considerations
Hydroxyurea may raise serum uric acid levels, requiring dosage adjustment of uricosuric medications. 1 This is explicitly listed as a drug interaction in multiple dermatology guidelines for psoriasis management.
When hydroxyurea is used in patients at risk for hyperuricemia, allopurinol may be necessary to prevent symptomatic hyperuricemia, though it should be restricted to patients with symptomatic hyperuricemia to avoid the risk of xanthine accumulation with renal failure. 1
Clinical Context from Case Reports
In one documented case, a patient with chronic myeloid leukemia presenting with gouty arthritis was successfully treated with the combination of allopurinol, hydroxyurea, and analgesics, with complete resolution of arthritis within 2 weeks. 2 This case demonstrates that hydroxyurea can be used in patients with gout when appropriate prophylaxis with allopurinol is provided.
Another case report documented a patient on long-term hydroxyurea (500 mg twice daily) who required concurrent allopurinol (100 mg daily) to treat gout. 3 This further supports the association between hydroxyurea use and the need for uric acid management.
Practical Management Approach
Monitoring Requirements
Baseline monitoring should include history, physical examination, complete blood count, and assessment of renal function. 1
Ongoing monitoring should include monthly complete blood counts and semiannual physical examinations. 1
Monitor serum uric acid levels regularly in patients on hydroxyurea, particularly those with pre-existing hyperuricemia or gout. 1
Prophylaxis Strategy
Consider prophylactic allopurinol in patients with pre-existing hyperuricemia or gout who require hydroxyurea therapy. 1
Ensure adequate hydration (2.5-3 L fluid intake per day, considering individual cardiac and renal status) to facilitate uric acid clearance. 1
Sodium bicarbonate may be used to set urine pH to 6.4-6.8 for optimal uric acid clearance. 1
Important Caveats
While hydroxyurea causes biochemical hyperuricemia through renal tubular dysfunction, the clinical manifestation as symptomatic gout appears manageable with appropriate prophylaxis. 1 The medication can be continued in patients who develop hyperuricemia if urate-lowering therapy is initiated concurrently, as demonstrated in clinical practice. 2, 3
The key is proactive monitoring and early intervention with urate-lowering therapy rather than automatic discontinuation of hydroxyurea, particularly when the drug is essential for treating the underlying hematologic condition. 1, 2