Allopurinol (Zyloprim) vs Alternatives: Best Gout Meds Compared

TL;DR

• Allopurinol (Zyloprim) is the first‑line urate‑lowering drug but can cause rash, dose‑dependent kidney issues, and interactions.
• Febuxostat works similarly but is safer for patients with mild‑moderate renal impairment; watch for cardiovascular warnings.
• Probenecid is a uricosuric that helps kidneys dump uric acid; not suitable if you have kidney stones or severe CKD.
• Lesinurad is added to a xanthine oxidase inhibitor (usually allopurinol or febuxostat) to boost uric‑acid clearance; watch for sudden kidney injury.
• Pegloticase and topiroxostat are third‑line options for refractory gout; peg‑ is IV, topiroxostat is oral and used in Japan/Europe.

What is Zyloprim (Allopurinol)?

When you hear the name Allopurinol a xanthine oxidase inhibitor that reduces uric‑acid production, think of the drug that’s been the backbone of gout therapy since the 1960s. Sold under the brand Zyloprim, it blocks the enzyme that converts purines into uric acid, keeping blood levels in check and preventing painful flares.

Typical dosing starts at 100mg daily, climbing to 300mg or even 600mg in resistant cases. Most people tolerate it well, but the drug isn’t without quirks: a hypersensitivity rash (often called “allopurinol hypersensitivity syndrome”) can be life‑threatening, especially in patients with renal impairment or on high doses. That’s why many look for Allopurinol alternatives when side‑effects or drug interactions become a problem.

Why Seek Alternatives?

Gout isn’t just a toe‑pain story; it can lead to kidney stones, joint damage, and cardiovascular strain. While allopurinol works for ~80% of patients, several scenarios push you toward other options:

• Kidney disease: Allopurinol dose‑adjusts poorly; higher doses raise toxicity risk.
• Drug interactions: Concurrent azathioprine or warfarin may need dose tweaks.
• Allergy or rash: Even a mild skin reaction may signal a severe hypersensitivity later.
• Inadequate urate control: Some patients never hit the target <120µmol/L

When one of these flags pops up, clinicians weigh the pros and cons of other urate‑lowering agents. Below is a quick snapshot of the most common alternatives.

Febuxostat - A Modern Xanthine Oxidase Inhibitor

First approved in 2009, Febuxostat an oral xanthine oxidase inhibitor that lowers uric acid without needing renal dose adjustments offers a tidy solution for patients who can’t tolerate allopurinol’s renal limitations.

• Dosing: 40mg once daily, titrated to 80mg or 120mg if needed.
• Renal safety: No dose reduction required down to eGFR 30mL/min/1.73m².
• Side‑effects: Liver‑function bumps, mild rash, occasional gout flare during initiation.
• Cardiovascular note: FDA boxed warning for patients with existing heart disease; discuss risk‑benefit.

Clinical trials (e.g., FEATHER) showed febuxostat achieving target urate in ~70% of patients with stage3 CKD, outperforming allopurinol at comparable doses.

Probenecid - The Urate‑Excreting Partner

Probenecid a uricosuric drug that increases renal excretion of uric acid works the opposite way: instead of blocking production, it helps the kidneys throw excess uric acid out.

• Dosing: 250mg twice daily, max 2g per day.
• Best for: Patients with under‑excreted uric acid and good kidney function (eGFR>50).
• Contra‑indications: History of kidney stones, severe CKD, or concurrent nephrotoxic drugs.
• Side‑effects: GI upset, rash, and rare hemolysis in G6PD‑deficient individuals.

Because probenecid relies on the kidneys, it’s often paired with a low dose of allopurinol or febuxostat when a single agent can’t hit the target.

Lesinurad - The Boosting Add‑on

Approved in 2015, Lesinurad a selective uric‑acid reabsorption inhibitor used in combination with a xanthine oxidase inhibitor adds extra uric‑acid clearance to patients already on allopurinol or febuxostat.

• Dosing: 200mg or 400mg once daily, taken with a xanthine oxidase inhibitor.
• Renal caution: Not for eGFR<30; monitor serum creatinine.
• Side‑effects: Acute kidney injury, especially if volume‑depleted.

Studies (e.g., CLEAR 1 & 2) demonstrated an extra 12-15% of patients reaching urate<120µmol/L when lesinurad was added to febuxostat.

Pegloticase - The Intravenous Rescue

For the toughest cases, Pegloticase a recombinant uric‑acid oxidase given IV that converts uric acid to allantoin is a biotech option used when oral drugs fail.

• Dosing: 8mg IV infusion every two weeks.
• Indication: Chronic refractory gout with urate>480µmol/L despite max oral therapy.
• Side‑effects: Infusion reactions, anti‑pegloticase antibody formation, rare anaphylaxis.
• Monitoring: Serum uric acid should drop below 120µmol/L within 24h of first infusion.

Real‑world data from US clinics show ~70% of patients achieve target urate within three months, but the need for IV visits limits widespread use.

Topiroxostat - The Asian Contender

While not yet FDA‑approved, Topiroxostat a potent xanthine oxidase inhibitor marketed in Japan and Europe offers another oral route with a favorable renal profile.

• Dosing: 50mg twice daily, titrated to 200mg.
• Renal safety: Minimal dose adjustment needed down to eGFR20mL/min/1.73m².
• Side‑effects: Mild liver‑enzyme elevation, GI upset.
• Evidence: Phase‑III studies in Japan report 71% target‑urate achievement, comparable to febuxostat.

If you’re in the UK and can access through a clinical trial or compounding pharmacy, topiroxostat might become a useful alternative in the near future.

How to Choose the Right Therapy

Picking the best medication isn’t a one‑size‑fits‑all decision. Consider these five practical criteria:

1. Kidney function: eGFR<30mL/min pushes you toward febuxostat, topiroxostat, or low‑dose allopurinol with close monitoring.
2. Cardiovascular risk: If you have heart failure or recent MI, weigh febuxostat’s boxed warning against allopurinol’s broader safety record.
3. History of rash or hypersensitivity: Switch to a uricosuric (probenecid) or a newer xanthine oxidase inhibitor.
4. Urate‑excretion capacity: A 24‑hour urine uric‑acid test can tell if a uricosuric will help.
5. Patient preference & lifestyle: Oral daily pills are easier than bi‑weekly IV infusions; cost and NHS formulary status matter too.

Talk to your GP or rheumatologist about lab values, comorbidities, and how each drug fits your daily routine.

Quick Comparison Table

*Prices are indicative NHS pharmacy list prices (2025) and may vary by region.

Next Steps for Patients

1. Get baseline labs. Serum uric acid, eGFR, LFTs, and a 24‑hour urine uric‑acid test give a clear picture.

2. Discuss comorbidities. Heart disease, kidney disease, and medication list shape the safest option.

3. Trial a low dose. Start with the smallest effective dose of your chosen drug, then titrate every 2‑4 weeks.

4. Monitor closely. Check uric acid after 4 weeks; if you’re still >360µmol/L, adjust dose or add a second agent.

5. Stay proactive. Lifestyle tweaks-hydration, low‑purine diet, weight loss-boost any medication’s effectiveness.

Frequently Asked Questions

Can I switch from allopurinol to febuxostat without a washout period?

Yes. Because both are xanthine oxidase inhibitors, you can transition directly. Most clinicians stop allopurinol and start febuxostat the next day, monitoring uric acid for a week to avoid a flare.

Is probenecid safe if I have a history of kidney stones?

No. Probenecid increases uric‑acid excretion, which can raise stone‑forming risk. If you’ve had stones, a uricosuric is usually avoided.

What triggers allopurinol hypersensitivity syndrome?

High starting doses (≥300mg) in patients with renal impairment, plus concurrent drugs like azathioprine, raise the risk. Gradual dose titration and HLA‑B*58:01 screening in Asian populations lower the chance.

Do I need regular blood tests on pegloticase?

Yes. Check uric acid before each infusion and monitor liver enzymes and renal function monthly. If uric acid spikes above 360µmol/L, an antibody may have formed and the drug should be stopped.

Is topiroxostat available on the NHS?

Not yet. It’s licensed in Japan and some EU countries but hasn’t received UK market authorization. Patients may obtain it via clinical trials or private import.