Hydrochlorothiazide Should Be Switched to Alternative Antihypertensives in Patients with Gout
For patients with gout, hydrochlorothiazide should be switched to an alternative antihypertensive agent when feasible, with losartan being the preferred replacement. 1
Mechanism of Harm
Hydrochlorothiazide elevates serum uric acid levels through two mechanisms: it decreases renal uric acid excretion and increases reabsorption in the proximal tubule. 2 The FDA label explicitly warns that "hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics." 2
- Thiazide diuretics reduce renal clearance of uric acid, leading to sustained hyperuricemia that persists with chronic use 3
- Recent diuretic use within 48 hours increases the risk of recurrent gout attacks 3.6-fold (95% CI 1.4-9.7), with thiazide-specific risk at 3.2-fold 4
- This represents one of the most common iatrogenic causes of gout in hypertensive patients 5, 6
Evidence-Based Recommendation
The 2020 American College of Rheumatology guidelines provide a conditional recommendation to switch hydrochlorothiazide to an alternate antihypertensive in all patients with gout, regardless of disease activity. 1 This recommendation is echoed by the 2017 EULAR guidelines, which state that "when gout occurs in a patient receiving loop or thiazide diuretics, substitute the diuretic if possible." 1
Preferred Alternative Agents
First choice: Losartan
- The ACR conditionally recommends choosing losartan preferentially as an antihypertensive when feasible 1
- Losartan has modest uricosuric effects that actively lower serum uric acid levels, making it uniquely beneficial in gout patients 5, 6
Second choice: Calcium channel blockers
- These agents do not adversely affect uric acid levels and are appropriate alternatives 1, 5
- The 2017 ACC/AHA hypertension guidelines note that calcium channel blockers are effective antihypertensives without metabolic effects on uric acid 1
When Switching Is Not Feasible
If hydrochlorothiazide cannot be discontinued due to compelling cardiovascular indications:
- Initiate or optimize urate-lowering therapy (allopurinol or febuxostat) to counteract the hyperuricemic effect 5, 6
- Target serum uric acid <6 mg/dL (or <5 mg/dL for severe gout with tophi or frequent attacks) 1
- Co-administration of febuxostat 80 mg with hydrochlorothiazide 50 mg does not significantly impair febuxostat's urate-lowering efficacy, though serum uric acid levels are 6.5-9.5% higher than with febuxostat alone 7
Critical Caveats
Do not discontinue low-dose aspirin: The ACR strongly recommends against stopping low-dose aspirin in patients taking it for appropriate cardiovascular indications, despite its mild uric acid-elevating effects. 1 The cardiovascular benefits outweigh the gout risk.
Dose considerations: While the FDA notes that gout attacks remain "uncommon" at standard doses ≤50 mg/day of hydrochlorothiazide, the 2017 ACC/AHA guidelines emphasize using chlorthalidone preferentially over hydrochlorothiazide for hypertension due to superior cardiovascular outcomes. 1, 6 However, chlorthalidone also elevates uric acid and should similarly be avoided in gout patients when alternatives exist.
Timing of switch: The medication switch can be made at any time and does not need to wait for the intercritical period between gout attacks 1
Clinical Algorithm
- Identify all patients with gout currently on hydrochlorothiazide 1
- Assess cardiovascular indication: Determine if hydrochlorothiazide is essential or if alternatives are feasible 1
- Switch to losartan as first-line alternative if blood pressure control allows 1, 5
- Switch to calcium channel blocker if losartan is contraindicated or not tolerated 1, 5
- If switching is not possible: Initiate allopurinol starting at 100 mg daily, titrating by 100 mg every 2-4 weeks to achieve serum uric acid <6 mg/dL 1, 5
- Provide flare prophylaxis with colchicine 0.5-1 mg daily for at least 6 months when initiating urate-lowering therapy 1, 5