Allopurinol vs Gout Alternatives: Which Drug Wins?

Zyloprim (Allopurinol) is a xanthine oxidase inhibitor used to lower serum uric acid in gout and hyperuricemia. It works by blocking the enzyme that converts purines into uric acid, thereby preventing crystal formation in joints and kidneys.

• Allopurinol blocks uric‑acid production.
• Febuxostat does the same job with a different chemical backbone.
• Probenecid increases uric‑acid excretion.
• Lesinurad boosts the effect of uricosurics.
• Pegloticase breaks down uric acid directly.

Why compare these drugs?

Patients with gout often start on Allopurinol because it’s cheap and well‑studied. Yet up to 30% of people either don’t reach target uric‑acid levels or develop side effects. When that happens, clinicians look at alternatives. This guide helps you understand the options, weigh pros and cons, and decide when a switch makes sense.

How Allopurinol works - the basics

Allopurinol is a xanthine oxidase inhibitor that reduces the conversion of hypoxanthine and xanthine into uric acid. Typical adult dosing starts at 100mg daily, titrating up to 300mg or 400mg based on serum uric‑acid levels and renal function. The drug is excreted unchanged by the kidneys, so dose adjustments are needed for eGFR<30mL/min. Common side effects include rash, elevated liver enzymes, and rare but serious Stevens‑Johnson syndrome.

Key alternative agents

Below are the most frequently prescribed alternatives, each with a distinct mechanism.

Typical dose: 40mg daily, titrated to 80mg or 120mg. It’s metabolized by the liver, so renal dose reduction isn’t required, but caution is advised in severe liver disease.

Standard dosing: 250mg twice daily, possibly up to 1g twice daily. It works best when kidney function is normal (eGFR>60mL/min) and can increase the risk of kidney stones.

Dosage: 200mg once daily with a uricosuric. It reduces the renal transporter URAT1, enhancing uric‑acid excretion. Liver function must be monitored because of occasional transaminase spikes.

Given as 8mg bi‑weekly infusion. It converts uric acid to allantoin, which is far more soluble. Because of infusion reactions and high cost, it’s reserved for patients who have failed at least two oral agents.

Direct comparison table

Choosing the right therapy - decision criteria

When you or your doctor weigh options, look at five practical factors:

1. Uric‑acid target achievement. If Allopurinol at 300mg still leaves serum urate >6mg/dL, consider stepping up.
2. Kidney function. Patients with eGFR<30mL/min often need dose‑reduced Allopurinol or switch to Febuxostat.
3. Allergy or hypersensitivity history. Prior rash to Allopurinol pushes you toward Febuxostat or a uricosuric.
4. Cost and insurance coverage. Generic Allopurinol wins on price; Pegloticase may be prohibitive unless covered by specialised schemes.
5. Comorbidities. Liver disease favors Allopurinol; cardiovascular risk flags have led some clinicians to avoid Febuxostat after the CARES trial signals.

Putting these together into a simple decision tree (Allopurinol → assess response → consider Febuxostat or Probenecid → add Lesinurad if needed → reserve Pegloticase) keeps the treatment plan logical.

Safety profiles - side‑effects to watch

Allopurinol can cause rash, especially in patients with HLA‑B*58:01 allele (common in Asian descent). Baseline liver function tests (LFTs) and renal labs are mandatory before starting.

Febuxostat shows a slightly higher rate of cardiovascular events in the CARES trial, so patients with prior myocardial infarction need careful monitoring.

Probenecid raises urinary uric‑acid concentration, increasing stone risk; hydration is key.

Lesinurad adds a small liver‑enzyme bump in ~5% of users; stop if ALT/AST >3× ULN.

Pegloticase can trigger infusion‑related anaphylaxis; pre‑medicate with antihistamines and monitor vitals during the first three doses.

Practical monitoring checklist

• Baseline serum urate, creatinine, eGFR, ALT/AST.
• Re‑check urate 2-4weeks after dose change.
• Watch for rash, especially within the first 6weeks.
• For uricosurics, ensure urine pH >6 and 2L fluid intake daily.
• Document any cardiovascular symptoms if on Febuxostat.

Related concepts and next steps

Understanding gout fully means looking at diet, genetics, and comorbidities. While this article sits under the Medicine umbrella, you may want to explore:

• Hyperuricemia risk factors (obesity, alcohol, diuretics).
• Non‑pharmacologic gout management (low‑purine diet, weight loss).
• Monitoring tools like the Urate‑to‑Creatinine Ratio for dose adjustments.
• Future therapies in development, such as selective IL‑1 inhibitors.

These topics deepen your grasp of why a drug works and when it’s the right fit.