How does chlorothiazide affect gout?

Chlorothiazide and Gout: Impact and Management

Thiazide diuretics like chlorothiazide significantly increase the risk of gout and should be switched to an alternative antihypertensive medication when feasible in patients with gout.

Mechanism and Risk

• Chlorothiazide and other thiazide diuretics reduce uric acid excretion by the kidneys, leading to elevated serum urate levels and increased risk of gout 1
• In randomized controlled trials, thiazide diuretics have been shown to increase the risk of gout significantly, with rate ratios of 6.3-11.8 compared to placebo 2
• Chlorothiazide can cause hyperuricemia even at standard doses, potentially precipitating acute gout attacks in susceptible individuals 3
• The risk of gout is highest with combined use of loop and thiazide diuretics (adjusted OR 4.65), but significant even with thiazide diuretics alone (adjusted OR 1.70-2.30) 4

Management Recommendations for Patients with Gout

• The American College of Rheumatology (2020) conditionally recommends switching hydrochlorothiazide (and by extension other thiazide diuretics like chlorothiazide) to an alternate antihypertensive when feasible in patients with gout 5
• When treating hypertension in patients with gout, losartan is preferentially recommended as it has uricosuric effects that can help lower serum urate levels 5, 1
• Calcium channel blockers are also appropriate alternatives for patients with gout as they do not adversely affect uric acid levels 5, 1
• For patients who must remain on diuretic therapy, more aggressive urate-lowering therapy may be needed to control gout 5

Monitoring and Prevention

• Patients on chlorothiazide should be monitored for hyperuricemia and symptoms of gout, particularly when first starting therapy 3
• The FDA label for chlorothiazide specifically warns that "hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazides" 3
• The risk of gout with chlorothiazide appears dose-dependent; using the lowest effective dose may reduce but not eliminate this risk 6
• In patients with a history of gout, chlorothiazide should be used with caution unless the patient is already on uric acid-lowering therapy 5

Alternative Approaches

• The European League Against Rheumatism (EULAR) recommends that "when gout occurs in a patient receiving loop or thiazide diuretics, substitute the diuretic if possible" 5
• For hypertension management in gout patients, EULAR specifically recommends considering losartan or calcium channel blockers as alternatives 5
• Weight loss, limiting alcohol intake (especially beer and spirits), and limiting purine-rich foods are conditionally recommended lifestyle modifications for patients with gout, regardless of medication use 5

Thiazide diuretics remain important medications for managing hypertension and heart failure, but their well-established effect on increasing serum urate levels makes them problematic for patients with gout. When possible, alternative antihypertensive medications should be considered in these patients to prevent recurrent gout attacks and improve quality of life.