What medications can cause gout?

Medications That Can Cause Gout

Diuretics—particularly thiazide and loop diuretics—are the most common medications that cause gout by reducing renal uric acid excretion and elevating serum urate levels. 1

Primary Culprit Medications

Diuretics (Highest Risk)

• Thiazide diuretics (e.g., hydrochlorothiazide) and loop diuretics (e.g., furosemide) are among the most common gout-inducing medications, reducing uric acid excretion by the kidneys and leading to hyperuricemia 1
• Hydrochlorothiazide at standard doses (≤50 mg/day) increases serum uric acid levels, though actual gout attacks remain relatively uncommon at these doses 1
• Furosemide is specifically associated with increased risk of gouty arthritis, particularly when used concomitantly with cyclosporine due to combined hyperuricemic effects 2
• The rising prevalence of gout in recent decades has been partly attributed to widespread prescription of these diuretics for cardiovascular diseases 1

Immunosuppressants

• Calcineurin inhibitors (cyclosporine and tacrolimus), commonly used in organ transplant recipients, elevate serum urate levels and impair renal urate excretion 1
• Concomitant use of cyclosporine and furosemide is associated with increased risk of gouty arthritis 2

Cardiovascular Medications

• Low-dose aspirin can elevate serum urate levels, though guidelines do not recommend discontinuation when used for cardiovascular prophylaxis 1
• Beta-blockers significantly contribute to hyperuricemia by reducing glomerular filtration rate and raising serum uric acid levels 3

Other Medications

• Niacin, used for hyperlipidemia, increases serum urate levels 1
• Pyrazinamide and ethambutol (anti-tuberculosis drugs) interfere with renal tubular excretion of urate 4

Clinical Management Algorithm

Step 1: Identify and Assess Necessity

• Review all current medications for gout-inducing potential 1
• Determine if the offending medication is essential for managing comorbidities 1

Step 2: Consider Discontinuation or Switching

• For thiazide/loop diuretics: Discontinue if possible and not essential for managing comorbidities 1
• Switch to losartan (angiotensin receptor blocker) as the preferred alternative for hypertension, as it has uricosuric effects that increase urinary uric acid excretion by approximately 25% and reduce serum uric acid by 20-47 μmol/L 5
• Consider calcium channel blockers as another alternative that does not adversely affect uric acid levels 1, 5

Step 3: Alternative Strategies When Switching Is Not Feasible

• When diuretics cannot be discontinued due to compelling indications, initiate or optimize urate-lowering therapy (allopurinol or febuxostat) to counteract the hyperuricemic effect 1
• Target serum uric acid <6 mg/dL (or <5 mg/dL for severe gout) 1
• For patients requiring calcineurin inhibitors, more aggressive urate-lowering therapy may be needed 1

Step 4: Consider Uricosuric Alternatives for Other Conditions

• For hyperlipidemia: Fenofibrate has uricosuric effects, reducing serum uric acid by approximately 20% and increasing renal uric acid clearance by about 30%, though guidelines recommend against switching solely for gout management 1, 5

Important Clinical Caveats

• Do not discontinue low-dose aspirin for cardiovascular prophylaxis solely due to gout risk, as the cardiovascular benefits outweigh the modest hyperuricemic effect 1
• Avoid abrupt discontinuation of antihypertensives without an alternative plan in patients requiring blood pressure control 5
• Monitor renal function and potassium levels when switching to losartan, particularly in patients with chronic kidney disease 5
• The decision to continue or switch medications must weigh cardiovascular benefits against gout risk, particularly in patients with established cardiovascular disease where discontinuation may not be appropriate 1
• While hydrochlorothiazide increases uric acid levels biochemically, the absolute risk of developing clinical gout attacks remains relatively low at standard therapeutic doses (≤50 mg/day) 1