Does furosemide (loop diuretic) increase the risk of developing gout?

Furosemide and Gout Risk

Furosemide significantly increases the risk of developing gout due to its effects on renal uric acid handling, with the FDA label specifically noting that concomitant use with cyclosporine is associated with increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia. 1

Mechanism of Furosemide-Induced Hyperuricemia

Furosemide increases gout risk through several mechanisms:

1. Decreased Uric Acid Excretion:

   • Furosemide decreases urinary excretion of uric acid by approximately 40% 2
   • It reduces fractional clearance of uric acid by 45% 2
   • These effects occur within 1-2 hours after administration

2. Plasma Uric Acid Elevation:

   • Furosemide increases plasma uric acid concentration by 6% within 1.5 hours of administration 2
   • With long-term use, uric acid excretion remains suppressed 3

3. Drug Interactions:

   • When combined with allopurinol (a common gout medication), furosemide increases serum urate levels despite elevated plasma oxypurinol (the active metabolite of allopurinol) 4
   • This interaction attenuates the hypouricemic effects of allopurinol treatment

Clinical Evidence

The American College of Rheumatology recognizes that thiazide and loop diuretics (including furosemide) increase the risk of gout attacks by reducing uric acid excretion and competing with urate for renal tubular secretion 5. This is particularly relevant for patients with:

• Hypertension requiring diuretic therapy
• Heart failure
• Cirrhosis with ascites
• Renal impairment

The European League Against Rheumatism (EULAR) guidelines specifically recommend stopping diuretics when possible in patients with gout, noting that diuretics are a common risk factor with an odds ratio of 1.72 (95% CI, 1.67 to 1.76) for developing gout 6.

Management Recommendations for Patients on Furosemide

1. Consider Alternative Medications:

   • If clinically appropriate, discontinue furosemide in patients who develop gout 6, 5
   • For hypertension, consider losartan (has uricosuric properties) 6
   • For hyperlipidemia, consider fenofibrate (has uricosuric effects) 6

2. Monitoring:

   • Patients on furosemide should be monitored for elevated serum urate levels and signs of gout 5
   • This is particularly important in patients with existing renal impairment

3. Urate-Lowering Therapy:

   • Target lower serum urate levels (<6 mg/dL or <5 mg/dL in severe cases) when initiating urate-lowering therapy in patients taking furosemide 5
   • Allopurinol dosing may need adjustment due to the interaction with furosemide 4

Special Considerations

• Elderly Patients: Impaired renal function is the primary reason for late-onset gout in elderly individuals, making them particularly susceptible to furosemide-induced gout 5

• Heart Failure Patients: Despite the increased risk of gout, furosemide may be necessary for managing heart failure symptoms. In these cases, prophylactic urate-lowering therapy might be considered 6

• Cirrhosis Patients: Furosemide is commonly used for ascites management, but alternatives or dose adjustments should be considered if gout develops 6

In summary, furosemide clearly increases the risk of gout through its effects on renal handling of uric acid. When possible, alternative medications should be considered for patients who develop gout while on furosemide therapy. When furosemide cannot be discontinued, appropriate monitoring and management of hyperuricemia are essential.