Association Between Gout Flares and HCTZ
Yes, there is a well-established association between hydrochlorothiazide (HCTZ) use and gout flares, as thiazide diuretics reduce renal urate excretion and increase serum uric acid levels, thereby triggering gout attacks in susceptible patients. 1, 2
Mechanism of HCTZ-Induced Hyperuricemia
Thiazide diuretics like HCTZ suppress urate excretion through the kidneys, leading to elevated serum uric acid concentrations that can precipitate monosodium urate crystal formation in joints 2
With prolonged HCTZ use, urate excretion falls significantly while the initial diuretic effect on other electrolytes diminishes, creating a persistent hyperuricemic state 2
HCTZ is specifically identified as a drug that reduces renal function and leads to reduced uric acid elimination, making it a recognized risk factor for gout development and flare precipitation 1
Clinical Implications for Gout Management
When HCTZ Cannot Be Discontinued
If HCTZ must be continued for hypertension management, initiate urate-lowering therapy (ULT) with allopurinol as the first-line agent to counteract the hyperuricemic effect 3, 4
The American College of Rheumatology strongly recommends allopurinol for patients with frequent gout flares (≥2/year), which may develop in patients on chronic HCTZ therapy 3
Start allopurinol at 100 mg daily and titrate every 2-5 weeks to achieve serum urate <6 mg/dL, with concomitant anti-inflammatory prophylaxis (colchicine 0.5-1 mg/day, NSAIDs, or low-dose prednisone) for 3-6 months 3
Drug Interaction Considerations
Co-administration of HCTZ with febuxostat does not significantly impair febuxostat's urate-lowering efficacy, though serum uric acid levels may be 6.5-9.5% higher compared to febuxostat alone 5
No dose adjustment for febuxostat is necessary when administered with HCTZ, making it a viable alternative ULT option if allopurinol is not tolerated 5
Common Pitfalls to Avoid
Do not assume that starting ULT will immediately prevent flares—the initial months of ULT can paradoxically increase flare frequency due to urate crystal mobilization, which is why prophylaxis is mandatory 3
Avoid stopping HCTZ abruptly during an acute gout flare without cardiology consultation if it was prescribed for heart failure or resistant hypertension, as the cardiovascular risks may outweigh gout concerns 1
In patients with chronic kidney disease (CKD stage ≥3) who are on HCTZ, the combination creates particularly high risk for gout progression and tophi formation, warranting earlier and more aggressive ULT initiation 6, 3
Alternative Antihypertensive Strategies
Consider switching to alternative antihypertensives that do not elevate uric acid, particularly in patients with recurrent gout flares despite ULT 1
Emerging evidence suggests SGLT2 inhibitors have uricosuric properties and may be beneficial in patients with both hypertension/diabetes and gout, though this represents an evolving treatment paradigm 7