Medications That Contribute to Gout

Common Medications That Increase Gout Risk

• Thiazide diuretics and loop diuretics are among the most common medications that contribute to hyperuricemia and gout, as they reduce uric acid excretion by the kidneys, leading to elevated serum urate levels, according to the American College of Rheumatology 1, 2
• Calcineurin inhibitors, such as cyclosporine and tacrolimus, commonly used in organ transplant recipients, can elevate serum urate levels, as stated by the American College of Rheumatology 1, 2
• Low-dose aspirin can elevate serum urate levels, though the American College of Rheumatology guidelines do not recommend discontinuation when used for cardiovascular prophylaxis, with a moderate strength of evidence 1, 3
• Niacin, commonly used for hyperlipidemia, can increase serum urate levels, according to the American College of Rheumatology 1, 2

Management Strategies for Medication-Induced Gout

• Consider discontinuing thiazide or loop diuretics if possible and not essential for managing comorbidities, as recommended by the American College of Rheumatology and the European League Against Rheumatism 1, 4
• When treating hypertension in gout patients, consider using losartan preferentially as it has uricosuric effects, with a high strength of evidence, according to the American College of Rheumatology and the European League Against Rheumatism 4, 3
• For hyperlipidemia, fenofibrate has uricosuric effects, though guidelines recommend against switching cholesterol-lowering agents to fenofibrate solely for gout management, with a moderate strength of evidence, as stated by the American College of Rheumatology 3, 5

Special Considerations

• In patients with gout and hypertension, consider using calcium channel blockers or losartan, which do not adversely affect uric acid levels, as recommended by the European League Against Rheumatism 4
• For patients requiring diuretics, be aware that the uricosuric effects of certain medications, like losartan or fenofibrate, may help counteract the hyperuricemic effects of diuretics, with a low strength of evidence, according to the European League Against Rheumatism 4, 6
• In patients with gout and organ transplants who require calcineurin inhibitors, more aggressive urate-lowering therapy may be needed, as stated by the American College of Rheumatology 1

Hydrochlorothiazide and Gout Risk

Mechanism and Risk

• Hydrochlorothiazide can cause gout by elevating serum uric acid levels and reducing uric acid excretion, though actual gout attacks remain uncommon at standard doses (≤50 mg/day), according to the JNC 7 guidelines 7
• Uric acid levels will increase in many patients receiving a diuretic, but the JNC 7 guidelines emphasize that the occurrence of gout is uncommon with dosages ≤50 mg/day of hydrochlorothiazide or ≤25 mg of chlorthalidone 7, 8

Evidence from Clinical Studies

• The rising prevalence of gout in recent decades has been partly attributed to widespread prescription of thiazide and loop diuretics for cardiovascular diseases 9, 10

Dose-Related Considerations

• Higher doses add little additional antihypertensive efficacy but are associated more with hyperuricemia and other adverse effects 7

Clinical Management Recommendations

• The 2020 ACR guidelines conditionally recommend switching hydrochlorothiazide to an alternate antihypertensive when feasible for patients with gout, regardless of disease activity 11
• Consider using losartan preferentially as an antihypertensive when feasible, as it has uricosuric effects that can help lower uric acid levels 11

Important Caveats

• While hydrochlorothiazide increases uric acid levels biochemically, the absolute risk of developing clinical gout attacks remains relatively low at standard therapeutic doses, particularly when doses are kept at or below 50 mg/day 7
• The decision to continue or switch from hydrochlorothiazide should weigh the cardiovascular benefits of the medication against the gout risk, particularly in patients with established cardiovascular disease where discontinuation may not be appropriate 11

Hydrochlorothiazide and Gout Management

Mechanism of Harm and Clinical Impact

• The American College of Rheumatology recommends switching hydrochlorothiazide in gout patients, as it elevates serum uric acid levels and increases gout risk, with a conditional recommendation reflecting moderate certainty evidence 12, 13, 14

Management Algorithm

• For patients with established gout on hydrochlorothiazide, the American College of Rheumatology suggests switching to losartan as the preferred alternative antihypertensive, which has uricosuric effects that actively lower uric acid 12, 13, 14
• The European League Against Rheumatism recommends considering calcium channel blockers as another alternative that does not adversely affect uric acid levels 15
• When switching hydrochlorothiazide is not feasible, the European League Against Rheumatism suggests initiating or optimizing urate-lowering therapy, such as allopurinol or febuxostat, to counteract the hyperuricemic effect, with a target serum uric acid <6 mg/dL (or <5 mg/dL for severe gout) 15

Evidence Quality

• The 2020 American College of Rheumatology guidelines and the 2017 EULAR guidelines provide consensus across major rheumatology societies that the hyperuricemic effect of hydrochlorothiazide is clinically meaningful enough to warrant medication changes when feasible, with a conditional recommendation reflecting moderate certainty evidence 12, 13, 14, 15