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Allopurinol in Gout: When to Start, How to Dose, and When to Stop

Introduction

If you’ve ever treated or studied gout, you’ve met allopurinol — the go-to urate-lowering therapy (ULT) that changes the game for patients plagued by painful flares. But knowing when to start it, how to adjust it, and if ever to stop it is a nuanced skill — and it’s something both clinicians and medical students need to master.

Let’s break it down in a way that’s practical for clinical life and exam prep.

What Is Allopurinol?

Allopurinol is a xanthine oxidase inhibitor. By blocking the conversion of hypoxanthine to uric acid, it reduces serum urate levels — the root biochemical driver of gout. The ultimate goal: dissolve urate crystal deposits, prevent new crystal formation, and stop gout flares for good.

When to Start Allopurinol

Guidelines agree: not every patient with elevated uric acid needs allopurinol.The American College of Rheumatology (ACR 2020) and EULAR (2016) recommend initiating allopurinol in:

  1. Recurrent gout attacks — ≥2 flares/year

  2. Tophaceous gout — visible or imaging-confirmed

  3. Gouty joint damage on X-ray or other imaging

  4. First flare + high-risk profile:

    • Serum uric acid >9 mg/dL

    • Chronic kidney disease stage ≥3

    • History of urolithiasis

💡 Exam Tip: Asymptomatic hyperuricemia alone is not an indication — unless uric acid is very high with risk of uric acid nephropathy.

How to Start It Right

  • Timing: Preferably start after an acute flare has resolved — unless the patient is already on ULT or you use anti-inflammatory prophylaxis.

  • Initial dose:

    • Normal renal function: 100 mg daily

    • CKD stage ≥3: 50 mg daily

  • Titration: Increase every 2–5 weeks to hit target uric acid:

    • <6 mg/dL for most patients

    • <5 mg/dL for tophaceous/severe gout

  • Max dose: Up to 800 mg/day (in divided doses), adjusted for renal function.

Always give flare prophylaxis (e.g., colchicine 0.6 mg once or twice daily, or low-dose NSAID) for at least 3–6 months after starting or increasing the dose.

Why You Shouldn’t Stop When It’s Working

Patients sometimes ask, “My uric acid is normal now — can I stop?”The answer: No (with rare exceptions).

Here’s why:

  • Gout is chronic: Urate overproduction or underexcretion doesn’t go away unless the underlying cause is resolved.

  • Crystals linger: Even with a normal uric acid, monosodium urate crystals can remain in joints for months to years.

  • Relapse is common: Stopping ULT almost always leads to uric acid rebound and recurrent flares.

When to Stop Allopurinol

Stopping is rare and generally reserved for:

  • Severe adverse reaction (e.g., allopurinol hypersensitivity syndrome — rash, hepatitis, eosinophilia, renal failure).

  • Unmanageable intolerance despite desensitization.

  • Switching to another ULT (e.g., febuxostat, uricosuric agents).

Special Safety Notes

  • HLA-B*58:01 testing: Mandatory before starting in patients of Han Chinese, Thai, or Korean descent due to high risk of severe cutaneous reactions.

  • Renal monitoring: Dose to target urate, not just to creatinine — but adjust carefully in CKD.

Case Example

Before allopurinol: Uric acid 9.8 mg/dL, recurrent gout attacks, tophus on great toe.After 6 months of therapy: Uric acid 5.8 mg/dL, no new flares.

Plan: Continue allopurinol — goal maintained (<6 mg/dL), but crystals may still be present. Stopping now risks undoing all progress.

Quick Reference Table – Allopurinol Decisions

Scenario

Start?

Continue?

Stop?

≥2 flares/year

✅ Yes

✅ Yes

❌ No

Tophaceous gout

✅ Yes

✅ Yes

❌ No

First flare + high-risk

✅ Yes

✅ Yes

❌ No

Asymptomatic hyperuricemia

❌ No

Normal uric acid on therapy

✅ Yes

❌ No

Severe drug reaction

❌ No

✅ Yes


Key Takeaways

  • Start allopurinol in recurrent gout, tophaceous gout, or high-risk first flares.

  • Dose to target urate: <6 mg/dL (or <5 in severe cases).

  • Continue for life in most patients — stopping almost always means recurrence.

  • Screen high-risk ethnic groups for HLA-B*58:01 before starting.

If you’re a med student prepping for exams or a clinician aiming to perfect your gout game, remember:

Allopurinol is not a “flare treatment” — it’s a long-term crystal eradication strategy.

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