Can furosemide (Lasix) increase gout attacks in a patient being treated for hypertension or heart failure who has gout or hyperuricemia?

Can Furosemide (Lasix) Increase Gout Attacks?

Yes, furosemide significantly increases the risk of gout attacks and can precipitate hyperuricemia, as explicitly stated in the FDA drug label: "Asymptomatic hyperuricemia can occur and gout may rarely be precipitated" 1. However, the relationship is more complex than simple causation, and management strategies exist to mitigate this risk.

Mechanism and Evidence of Furosemide-Induced Hyperuricemia

Loop diuretics like furosemide are well-established risk factors for gout, with the European League Against Rheumatism documenting an odds ratio of 1.72 for diuretic-associated gout 2. The mechanism involves:

• Reduced renal uric acid excretion: Furosemide competes for the same organic acid transport system in the proximal tubule that excretes uric acid, leading to decreased urinary urate clearance 3
• Volume depletion effects: Diuretic-induced volume contraction enhances proximal tubular reabsorption of urate 3
• Direct elevation of serum uric acid: Studies demonstrate that patients treated with diuretics have significantly higher serum uric acid levels compared to those not taking these medications 3

A critical drug interaction exists between furosemide and allopurinol: furosemide increases plasma oxypurinol levels while paradoxically failing to lower serum urate, effectively attenuating the hypouricemic effects of allopurinol therapy 4. This means patients on both medications may have inadequate gout control despite seemingly appropriate allopurinol dosing.

Guideline-Based Management Algorithm

Step 1: Assess Whether Furosemide Can Be Discontinued

The American College of Rheumatology conditionally recommends switching hydrochlorothiazide (and by extension, other diuretics) to alternative antihypertensives in gout patients, regardless of disease activity 5. The 2012 ACR guidelines specifically note that "widespread prescription of thiazide and loop diuretics for cardiovascular diseases" contributes to rising gout prevalence 6.

• If furosemide is being used for hypertension alone: Switch to losartan as the preferred alternative, which has unique uricosuric properties that increase urinary uric acid excretion by approximately 25% and reduce serum uric acid by 20-47 μmol/L 5
• Target losartan dose: 100 mg once daily for optimal cardiovascular and urate-lowering benefits 5
• Alternative options: Calcium channel blockers are also recommended as they do not increase serum uric acid levels 5

Step 2: When Furosemide Cannot Be Discontinued

For patients with compelling indications (heart failure, severe volume overload), the benefits of diuretic therapy must be carefully weighed against gout risk 5. The 2007 emergency medicine guidelines emphasize that "diuretics should be administered judiciously" given their association with adverse outcomes 6.

In these situations:

• Optimize urate-lowering therapy: Recognize that higher doses of allopurinol may be needed due to the furosemide-oxypurinol interaction 4
• Consider adding fenofibrate: If the patient has concurrent hyperlipidemia, fenofibrate demonstrates uricosuric effects, reducing serum uric acid by approximately 20% 5
• Monitor serum uric acid regularly: The FDA label recommends periodic checking of uric acid levels in patients receiving furosemide 1

Step 3: Address Concurrent Cyclosporine Use

The FDA explicitly warns that "concomitant use of cyclosporine and furosemide is associated with increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion" 1. This combination should be avoided when possible.

Important Caveats and Clinical Pitfalls

Conflicting evidence exists regarding whether diuretics truly cause gout versus serving as a marker for cardiovascular disease: One 2006 case-control study found that after adjustment for cardiovascular conditions, the incidence rate ratio for gout with diuretic use dropped to 0.6, suggesting that cardiovascular indications may confound the association 7. However, this single study contradicts the preponderance of guideline recommendations and the FDA drug label warning.

The most pragmatic interpretation: While cardiovascular disease itself may contribute to gout risk, furosemide independently elevates serum uric acid through direct pharmacologic mechanisms 3. Both factors likely contribute in clinical practice.

Common pitfall to avoid: Do not assume that patients on both furosemide and allopurinol have adequate urate control based solely on allopurinol dose—the drug interaction may require dose adjustment 4.

Monitoring requirements per FDA label: Check serum electrolytes (particularly potassium), CO2, creatinine, BUN, and uric acid frequently during initial therapy and periodically thereafter 1.