Can hydrochlorothiazide (HCTZ) worsen gout?

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From the Guidelines

Yes, hydrochlorothiazide (HCTZ) can worsen gout. This commonly prescribed thiazide diuretic, typically used at doses of 12.5-50 mg daily for hypertension, increases uric acid levels in the blood by reducing uric acid excretion in the kidneys. This elevation in uric acid can trigger gout flares in susceptible individuals or exacerbate existing gout. According to the 2020 American College of Rheumatology guideline for the management of gout 1, switching hydrochlorothiazide to an alternate antihypertensive when feasible is conditionally recommended for patients with gout, regardless of disease activity.

Key Considerations

  • Patients with a history of gout should be particularly cautious when taking HCTZ and should inform their healthcare provider about any gout history before starting this medication.
  • If you're taking HCTZ and develop symptoms of gout such as sudden, severe joint pain (often in the big toe), redness, swelling, or warmth in a joint, contact your doctor promptly.
  • Alternative antihypertensive medications that don't affect uric acid levels, such as calcium channel blockers or angiotensin receptor blockers, may be more appropriate for patients with gout.
  • In some cases, your doctor might prescribe allopurinol or febuxostat alongside HCTZ to help control uric acid levels if the diuretic is deemed necessary for your blood pressure management.
  • The American College of Rheumatology guideline also recommends choosing losartan preferentially as an antihypertensive agent when feasible for patients with gout, regardless of disease activity 1.

Management of Gout

The management of gout involves a comprehensive approach, including lifestyle modifications, medication, and alternative therapies. For patients with gout, it is essential to monitor uric acid levels and adjust medications accordingly. The 2020 American College of Rheumatology guideline provides conditional recommendations for the management of concurrent medications in patients with gout, including the use of hydrochlorothiazide 1.

Evidence-Based Recommendations

The evidence-based recommendations for the management of gout emphasize the importance of individualized treatment plans, taking into account the patient's medical history, disease activity, and potential drug interactions. According to a study published in the Annals of the Rheumatic Diseases 1, diuretics should be stopped if possible in patients with gout, and alternative antihypertensive treatment without diuretics should be considered. The study also highlights the potential benefits of using losartan and fenofibrate in patients with gout, due to their uricosuric effects.

From the FDA Drug Label

Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics.

  • Hydrochlorothiazide can worsen gout by precipitating hyperuricemia or acute gout in certain patients, as it decreases the excretion of uric acid 2.
  • Patients taking hydrochlorothiazide should be monitored for signs of gout or hyperuricemia.
  • The use of hydrochlorothiazide may require adjustment of treatment for patients with gout or hyperuricemia 2.

From the Research

Hydrochlorothiazide and Gout

  • Hydrochlorothiazide (HCTZ) is a diuretic that can affect uric acid levels in the body, potentially worsening gout symptoms 3, 4, 5, 6.
  • Studies have shown that HCTZ can increase serum uric acid levels, which can lead to gout attacks 4, 5.
  • One study found that HCTZ decreased urate excretion, which can contribute to the development of gout 3.
  • Another study found that thiazide diuretics, including HCTZ, can increase the risk of initiating anti-gout therapy, particularly at doses of 25 mg/day or higher 6.
  • However, it's worth noting that not all studies have found a significant association between HCTZ use and gout symptoms 7.

Mechanism of Action

  • HCTZ works by increasing the excretion of sodium and water in the urine, which can lead to a decrease in urate excretion and an increase in serum uric acid levels 3, 4.
  • The exact mechanism by which HCTZ worsens gout is not fully understood, but it's thought to be related to its effects on uric acid metabolism and excretion 5, 6.

Clinical Implications

  • Patients with gout who are taking HCTZ should be monitored closely for signs of worsening gout symptoms, such as increased frequency or severity of attacks 7, 6.
  • Alternative treatments, such as potassium-sparing diuretics or uricosuric agents, may be considered for patients with gout who require diuretic therapy 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Effects of diuretics on urate and calcium excretion.

Archives of internal medicine, 1981

Research

Hydrochlorothiazide and spironolactone in hypertension.

Clinical pharmacology and therapeutics, 1979

Research

Thiazide diuretics and the initiation of anti-gout therapy.

Journal of clinical epidemiology, 1997

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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