Allopurinol vs. Other Gout Medicines: How Zyloprim Stacks Up

Zyloprim (Allopurinol) is a xanthine oxidase inhibitor used to lower uric acid in gout and hyperuricemia. It works by blocking the enzyme that turns purines into uric acid, keeping blood levels in check and preventing painful attacks. While Allopurinol has been the backbone of urate‑lowering therapy (ULT) for decades, newer drugs promise faster relief or fewer side effects. Choosing the right option depends on kidney function, cost, drug‑drug interactions, and how aggressively you need to drop uric acid. This guide compares Allopurinol with the most common alternatives - Febuxostat, Probenecid, Lesinurad, and Pegloticase - so you can see where each fits in a real‑world treatment plan.

Why Compare Urate‑Lowering Options?

Gout isn’t just a flashy foot swelling; it’s linked to kidney stones, cardiovascular disease, and reduced quality of life. The goal of any ULT is two‑fold: keep serum uric acid (SUA) below 6mg/dL and prevent flares. Yet patients differ widely. Some have normal kidneys, others struggle with chronic kidney disease (CKD). Some want a pill they can take once a day, while others need something that works when oral meds fail. By laying out the pharmacology, dosing, safety, and cost of each drug, you can match the therapy to the patient’s profile instead of forcing a one‑size‑fits‑all approach.

Allopurinol: The Classic Choice

Allopurinol is a xanthine oxidase inhibitor (XO‑I) that reduces uric acid production. Typical starting dose is 100mg once daily, titrated up to 300mg or 400mg depending on SUA response and renal function. In patients with an eGFR<30mL/min, the dose is usually capped at 100-200mg daily to avoid accumulation.

Key strengths:

• Well‑studied: >30years of clinical data.
• Inexpensive: generic versions cost a few pennies per tablet.
• Effective for most patients: achieves target SUA in 70‑80% when adhered to.

Common side effects include rash, transient liver enzyme elevation, and-rare but serious-Allopurinol Hypersensitivity Syndrome (AHS). Because AHS is more likely in patients with renal impairment or when dosing exceeds recommendations, careful dose titration and HLA‑B*58:01 screening in high‑risk ethnic groups (e.g., Asian ancestry) are advised.

Febuxostat: A Non‑Purine XO‑I

Febuxostat is a selective, non‑purine xanthine oxidase inhibitor approved for patients who cannot tolerate Allopurinol or need additional uric‑lowering power.

It starts at 40mg once daily, with a usual maintenance dose of 80mg; some patients require 120mg for stubborn hyperuricemia. Unlike Allopurinol, Febuxostat does not require renal dose adjustment, making it a go‑to for moderate CKD (eGFR15-60mL/min). However, cardiovascular safety warnings emerged after the CARES trial showed higher all‑cause mortality in patients with established heart disease.

Pros:

• Effective at lower doses; can achieve SUA<5mg/dL.
• No dose reduction needed for most renal impairments.

Cons:

• Costlier than generic Allopurinol.
• Potential increased CV risk; caution in patients with coronary artery disease.

Probenecid: The Urate Reabsorption Blocker

Probenecid is a uricosuric agent that blocks renal tubular reabsorption of uric acid, increasing its excretion.

Typical dosing is 250mg twice daily, titrated up to 500mg three times daily. It works only if the kidneys can handle the extra uric acid load, so it’s unsuitable for patients with eGFR<30mL/min or a history of kidney stones.

Advantages include synergy with low‑dose Allopurinol (combined therapy can achieve deeper SUA reductions) and a lower risk of systemic side effects. Drawbacks are the need for good hydration, risk of nephrolithiasis, and drug interactions-especially with penicillins and NSAIDs, where Probenecid can raise plasma levels.

Lesinurad: A Newer URAT1 Inhibitor

Lesinurad is a selective inhibitor of the uric acid transporter 1 (URAT1), approved only in combination with a xanthine oxidase inhibitor.

It comes in 200mg or 400mg tablets taken once daily with Allopurinol or Febuxostat. Lesinurad enhances uric acid excretion, helping patients who have not reached target SUA despite optimal XO‑I dosing.

Key points:

• Requires concomitant XO‑I; not a standalone therapy.
• Can increase serum creatinine; monitor renal function.
• Higher cost and limited availability in some regions.

Pegloticase: The Intravenous Option for Refractory Gout

Pegloticase is a recombinant uricase enzyme that converts uric acid into the soluble metabolite allantoin, administered by IV infusion.

It's reserved for patients with severe, treatment‑resistant gout who have failed or cannot tolerate oral ULTs. The dosing schedule is 8mg every two weeks, but anti‑drug antibodies develop in up to 40% of patients, often leading to loss of efficacy and infusion reactions.

Pros:

• Can reduce SUA to <1mg/dL rapidly.
• Improves tophi resolution.

Cons:

• High cost (thousands of pounds per infusion).
• Requires clinic visits for IV administration.
• Risk of severe anaphylaxis; pre‑medication with antihistamines is standard.

Side‑by‑Side Comparison

How to Choose the Right Therapy

Think of the decision as a flowchart that starts with two clinical anchors: kidney function and previous drug tolerance.

1. Renal function: If eGFR≥60mL/min, Allopurinol or Febuxostat are both viable. Below 30mL/min, Febuxostat or a reduced‑dose Allopurinol are safer; uricosurics (Probenecid, Lesinurad) are usually off‑label.
2. Allergy or hypersensitivity: Any history of rash or AHS pushes you toward Febuxostat or a non‑XO‑I option.
3. Cardiovascular risk: Patients with established coronary disease should stay on Allopurinol unless intolerant; weigh Febuxostat’s CV warning carefully.
4. Cost and adherence: Oral tablets (Allopurinol, Febuxostat, Probenecid) are easiest for daily adherence. If cost is a barrier, Allopurinol wins.
5. Refractory disease: When SUA stays >6mg/dL despite optimal oral therapy, add Lesinurad or switch to Pegloticase for rapid control.

Ultimately, regular monitoring of SUA, renal labs, and patient‑reported outcomes guides dose tweaks. Target SUA <5mg/dL for most; <4mg/dL if tophi are present.

Practical Tips & Pitfalls

• Start low, go slow: Initial doses are deliberately modest to avoid sudden uric acid shifts that can precipitate flares.
• Prophylaxis during initiation: Low‑dose colchicine or NSAIDs for the first 3‑6weeks reduce acute gout attacks caused by mobilizing urate.
• Drug interactions: Allopurinol and Febuxostat interact with azathioprine, mercaptopurine, and theophylline. Probenecid raises levels of penicillins and sulfonamides.
• Monitoring: Check liver enzymes and CBC at baseline, then after 2‑4weeks of any new XO‑I. For Lesinurad, repeat serum creatinine after the first month.
• Genetic screening: HLA‑B*58:01 testing before starting Allopurinol in Asian‑heritage patients cuts AHS risk dramatically.

Related Concepts and Next Steps

Understanding gout fully involves a few adjacent topics. Uric Acid is the end‑product of purine metabolism and the culprit in crystal formation. Lifestyle changes-reducing purine‑rich foods, limiting alcohol, and maintaining a healthy weight-lay the groundwork for any medication to work. For patients with frequent flares, exploring Colchicine prophylaxis or IL‑1 blockers (e.g., anakinra) can be a next‑level strategy. Finally, keep an eye on emerging therapies like selective URAT1 inhibitors beyond Lesinurad, which may someday replace the need for combination regimens.