Can chlorthalidone (a diuretic) cause an arthritis flareup in patients with a history of gout or other forms of arthritis?

Can Chlorthalidone Cause an Arthritis Flareup?

Yes, chlorthalidone can directly precipitate gout flares by elevating serum uric acid levels and reducing renal uric acid excretion, making it a well-established trigger for acute gouty arthritis in susceptible patients. 1, 2

Mechanism of Gout Precipitation

Chlorthalidone, a thiazide-type diuretic, causes hyperuricemia through two mechanisms 2:

• Reduces renal uric acid excretion by competing for tubular secretion pathways
• Increases tubular reabsorption of uric acid in the proximal tubule

The FDA drug label explicitly warns that "hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone." 2

Clinical Evidence and Risk Magnitude

The risk is substantial and clinically meaningful 1, 3:

• Thiazide and thiazide-type diuretics are among the most common medications that contribute to hyperuricemia and gout 3
• The 2017 ACC/AHA hypertension guidelines specifically caution to "use with caution in patients with history of acute gout unless patient is on uric acid-lowering therapy" 1
• The European League Against Rheumatism identifies diuretics as a key risk factor that should be searched for in every person with gout 1

However, there is an important dose-response relationship 3:

• Gout attacks remain uncommon at standard doses (≤25 mg/day of chlorthalidone)
• Higher doses add little antihypertensive benefit but substantially increase hyperuricemia risk 3

Management Algorithm When Gout Develops

If a patient on chlorthalidone develops gout, follow this approach 4, 3:

1. First-line: Switch to losartan 4, 3

   • Losartan has unique uricosuric effects that actively lower serum uric acid
   • The American College of Rheumatology conditionally recommends switching chlorthalidone to an alternate antihypertensive when feasible 3
   • The European League Against Rheumatism specifically recommends losartan for hypertension management in gout patients 4

2. Alternative: Calcium channel blockers 4, 3

   • Do not adversely affect uric acid levels
   • Amlodipine showed 37% reduction in gout risk compared to chlorthalidone in the ALLHAT trial 5

3. If switching is not feasible 3:

   • Initiate or optimize urate-lowering therapy (allopurinol or febuxostat)
   • Target serum uric acid <6 mg/dL (or <5 mg/dL for severe gout)

Critical Caveats

Do not automatically discontinue chlorthalidone in all cases 3, 6:

• The decision must weigh cardiovascular benefits against gout risk
• Chlorthalidone is preferred over hydrochlorothiazide for cardiovascular outcomes based on prolonged half-life and proven trial reduction of CVD 1
• In patients with established cardiovascular disease or heart failure, discontinuation may not be appropriate 3
• A systematic review found that stopping diuretics in patients who develop gout is not consistently supported by evidence 6

Key patient factors to assess 2:

• History of gout or hyperuricemia
• Concurrent use of other medications that raise uric acid (low-dose aspirin, niacin, calcineurin inhibitors) 3
• Renal function status
• Cardiovascular disease burden requiring diuretic therapy

For acute gout treatment while on chlorthalidone 7, 8:

• NSAIDs remain first-line for acute flares (initiate as soon as possible)
• Colchicine, corticosteroids, or IL-1 inhibitors are alternatives
• Do not adjust urate-lowering therapy during an acute flare