Gout Drug Comparison Tool
Allopurinol (Zyloprim)
Class: Xanthine oxidase inhibitor
Starting Dose: 100 mg daily
Renal Adjustment: Yes, dose-reduce if CrCl < 30 mL/min
Key Advantage: Long track record, low cost
Main Safety Concern: Hypersensitivity syndrome (rare but serious)
Febuxostat
Class: Xanthine oxidase inhibitor
Starting Dose: 40 mg daily
Renal Adjustment: No dose adjustment needed for most renal impairment
Key Advantage: Similar potency, good for renal impairment
Main Safety Concern: Potential increased cardiovascular risk
Probenecid
Class: Uricosuric agent
Starting Dose: 250 mg twice daily
Renal Adjustment: Not recommended if CrCl < 30 mL/min
Key Advantage: Increases uric acid excretion
Main Safety Concern: Kidney stones, drug interactions
Lesinurad
Class: Uricosuric agent (URAT1 blocker)
Starting Dose: 200 mg once daily
Renal Adjustment: Monitor creatinine, avoid in severe renal impairment
Key Advantage: Enhances uric acid clearance
Main Safety Concern: Elevated creatinine, renal impairment risk
Pegloticase
Class: Recombinant uric acid oxidase
Administration: IV infusion every 2 weeks
Renal Adjustment: Reserved for refractory gout
Key Advantage: Effective for severe, treatment-resistant gout
Main Safety Concern: Infusion reactions, anti-drug antibodies
Comparison Summary Table
| Drug | Class | Typical Starting Dose | Renal Adjustment? | Key Advantage | Main Safety Concern |
|---|---|---|---|---|---|
| Allopurinol | Xanthine oxidase inhibitor | 100 mg daily | Yes, reduce dose if CrCl < 30 mL/min | Long track record, low cost | Hypersensitivity syndrome |
| Febuxostat | Xanthine oxidase inhibitor | 40 mg daily | No dose adjustment needed | Good for renal impairment | Potential CV risk |
| Probenecid | Uricosuric agent | 250 mg twice daily | Not recommended if CrCl < 30 mL/min | Increases excretion | Kidney stones, drug interactions |
| Lesinurad | Uricosuric agent (URAT1 blocker) | 200 mg once daily | Monitor creatinine | Enhances clearance | Elevated creatinine |
| Pegloticase | Recombinant uric acid oxidase | IV infusion every 2 weeks | Reserved for severe cases | Rescue therapy for refractory gout | Infusion reactions, antibodies |
How to Choose Your Medication
- Kidney Function: Adjust doses accordingly or choose alternatives like Febuxostat.
- Cardiovascular History: Avoid Febuxostat if there's a history of heart disease.
- Urate Targets: Consider combination therapy for aggressive lowering.
- Cost and Accessibility: Allopurinol remains the most affordable option.
Allopurinol is a xanthine oxidase inhibitor used to lower uric acid levels in patients with gout and hyperuricemia. Marketed under the brand name Zyloprim, it has been a first‑line therapy for decades. While it works well for many, newer agents promise better tolerance or faster urate reduction. Below you’ll find a plain‑English side‑by‑side look at Allopurinol and its most common competitors.
Key Takeaways
- Allopurinol blocks uric‑acid production; alternatives either block production, increase excretion, or break down existing urate.
- Febuxostat matches Allopurinol’s potency with fewer kidney‑related warnings, but may raise cardiovascular risk.
- Probenecid and Lesinurad boost uric‑acid excretion and work best when urate production is already low.
- Pegloticase is a rescue drug for refractory gout, given by infusion and reserved for severe cases.
- Choosing the right drug depends on kidney function, cardiovascular history, and how aggressively you need to lower serum urate.
Allopurinol (Zyloprim) - How It Works and Who Uses It
Allopurinol belongs to the xanthine oxidase inhibitors. By shutting down the enzyme that converts purines into uric acid, it reduces the amount of urate circulating in the blood. Typical dosing starts at 100mg daily and titrates up to 300mg or higher, depending on serum urate targets and kidney function.
Key benefits include:
- Long‑track record of effectiveness and low cost.
- Works well for patients with mild‑to‑moderate kidney impairment when dose‑adjusted.
Common side effects are skin rash, hypersensitivity (rare but serious), and liver‑enzyme elevations. The dreaded Allopurinol hypersensitivity syndrome can be fatal, so clinicians check HLA‑B*58:01 in high‑risk ethnic groups.
Popular Alternatives to Allopurinol
Below are the five drugs most often compared with Allopurinol for gout management.
Febuxostat
Febuxostat is another xanthine oxidase inhibitor. It is metabolized mainly by the liver, making it a go‑to option when kidneys can’t clear Allopurinol well. Starting dose is 40mg daily, titrating to 80mg or 120mg for tougher cases.
Pros: Similar urate‑lowering power, no dose‑adjustment needed for most renal impairment. Cons: Post‑marketing data link it to higher rates of cardiovascular events, especially in patients with prior heart disease.
Probenecid
Probenecid is a uricosuric agent that increases renal excretion of uric acid. It works best when the kidneys are already functioning, and when uric‑acid production is already controlled.
Typical dose: 250mg twice daily, max 2g per day. Side effects include kidney stones, gastric upset, and drug‑drug interactions via the organic anion transporter.
Lesinurad
Lesinurad is a newer uricosuric that blocks the URAT1 transporter, enhancing uric‑acid clearance. It is usually combined with a xanthine oxidase inhibitor (often Allopurinol or Febuxostat) because monotherapy can raise serum urate.
Dosage: 200mg once daily, paired with a base urate‑lowering drug. Watch for renal impairment and potential elevations in serum creatinine.
Pegloticase
Pegloticase is a recombinant uric‑acid oxidase enzyme given intravenously. It converts uric acid into allantoin, which the kidney easily excretes.
It's reserved for refractory gout that fails two oral agents. Infusions are every two weeks, but infusion reactions and the development of anti‑drug antibodies are common concerns.
Topiroxostat
Topiroxostat is a Japanese‑market xanthine oxidase inhibitor with a profile similar to Allopurinol but less reliance on renal clearance.
Available dose ranges from 60mg to 400mg daily. It is not yet FDA‑approved, limiting its use in the U.S.
Side‑by‑Side Comparison Table
| Drug | Class | Typical Starting Dose | Renal Adjustment? | Key Advantage | Main Safety Concern |
|---|---|---|---|---|---|
| Allopurinol | Xanthine oxidase inhibitor | 100mg daily | Yes, dose‑reduce if CrCl <30mL/min | Low cost, decades of experience | Severe hypersensitivity (HLA‑B*58:01) |
| Febuxostat | Xanthine oxidase inhibitor | 40mg daily | No major renal dosing needed | Effective in renal failure | Possible cardiovascular events |
| Probenecid | Uricosuric | 250mg BID | Not for eGFR <30mL/min | Rapid urate excretion | Kidney stones, drug interactions |
| Lesinurad | Uricosuric (URAT1 inhibitor) | 200mg daily + XOI | Use with caution if CrCl <30mL/min | Works synergistically with XOI | Renal function decline |
| Pegloticase | Uric‑acid oxidase enzyme | 8mg IV every 2weeks | Not limited by kidney function | Powerful in refractory gout | Infusion reactions, antibodies |
| Topiroxostat | Xanthine oxidase inhibitor | 60mg daily | Minimal renal adjustment | Potentially lower liver toxicity | Limited availability outside Japan |
When to Prefer Allopurinol Over Alternatives
If a patient has:
- Stable kidney function (eGFR >30mL/min) and no history of severe rash.
- No major cardiovascular disease.
- Affordability concerns - Allopurinol is generically priced under $10 per month in most markets.
Then Allopurinol remains the go‑to. Adjust the dose gradually to avoid a rapid drop in uric acid, which could trigger gout flares.
When Alternatives Might Be a Better Fit
Febuxostat shines for patients with chronic kidney disease (CKD stage3-4) because it bypasses renal clearance. However, if they have coronary artery disease, the physician should weigh the cardiovascular safety signal.
Probenecid or Lesinurad are useful when uric‑acid production is already well‑controlled (e.g., on a low dose Allopurinol) but serum urate stays above target. Their uricosuric effect adds the missing piece.
Pegloticase is reserved for refractory gout - patients who have tried at least two oral agents, still have ≥1 flare per month, and have tophi. Because it requires IV infusions and pre‑medication for reactions, it’s a specialist‑managed option.
Topiroxostat may become an alternative in regions where it’s approved, especially for patients who cannot tolerate Allopurinol due to liver concerns.
Practical Tips and Common Pitfalls
- Start low, go slow - increase Allopurinol or Febuxostat doses only after checking serum urate and renal labs.
- Screen high‑risk ethnic groups for HLA‑B*58:01 before prescribing Allopurinol.
- When adding a uricosuric, ensure urine pH is monitored; low pH can precipitate stones.
- Educate patients that urate‑lowering drugs don’t stop acute gout attacks; they need NSAIDs or colchicine for flares.
- Re‑check cardiovascular risk factors every 6months if the patient is on Febuxostat.
Frequently Asked Questions
Can I switch from Allopurinol to Febuxostat without a washout period?
Yes. Because both drugs act on the same enzyme, a direct switch is safe. Most clinicians stop Allopurinol and start Febuxostat at the usual 40mg dose the next day, then titrate based on urate levels.
Is Allopurinol safe for people with mild kidney disease?
Yes, but the dose should be reduced. For an eGFR between 30-50mL/min, a common regimen is 100mg daily; for eGFR <30, many clinicians cap at 100mg or use Febuxostat instead.
Why does my doctor recommend a uricosuric after I’ve started Allopurinol?
Allopurinol reduces how much uric acid is made, but some patients still produce enough to keep serum levels high. Adding a uricosuric like Probenecid or Lesinurad helps the kidneys dump the excess urate, achieving the target < 6mg/dL.
What are the signs of Allopurinol hypersensitivity?
Look for a sudden rash, fever, facial swelling, or liver/kidney dysfunction that appears within the first 2-3months of therapy. If any of these occur, stop the drug immediately and seek medical care.
Do I need to stay on a urate‑lowering drug for life?
Usually, yes. Gout is a chronic metabolic issue; stopping therapy often leads to a rebound in uric acid and new flares. Some patients can taper after years of stable control, but only under close supervision.
Next Steps for Patients and Clinicians
1. Review the patient’s kidney function, cardiovascular history, and medication list.
2. Choose a base agent (Allopurinol or Febuxostat) that matches the renal profile.
3. If serum urate stays above target, add a uricosuric (Probenecid or Lesinurad).
4. For refractory cases, consider referral for Pegloticase therapy.
5. Schedule follow‑up labs (uric acid, renal panel, liver enzymes) every 4-6weeks until the target is hit, then every 3-6months.
By weighing efficacy, safety, cost, and patient‑specific factors, you can pinpoint the right gout medication-whether that’s sticking with Allopurinol or moving to an alternative that better fits the individual’s needs.
Nikita Warner
October 1, 2025 AT 21:16When deciding between allopurinol and its alternatives, the primary considerations are renal function, cardiovascular risk, and cost. Allopurinol remains the most cost‑effective first‑line agent, especially when the dose is titrated to serum urate goals and renal function is taken into account. Dose reduction is recommended for patients with a creatinine clearance below 30 mL/min to avoid accumulation and potential hypersensitivity. In patients of Asian descent, testing for HLA‑B*58:01 can reduce the incidence of severe cutaneous adverse reactions. For those with moderate to severe renal impairment, febuxostat offers comparable urate‑lowering efficacy without the need for dose adjustment, though clinicians should remain vigilant for possible cardiovascular events. Uricosuric agents such as probenecid and lesinurad are useful adjuncts if the patient produces sufficient urine and has no history of nephrolithiasis; they require careful monitoring of renal parameters. Pegloticase should be reserved for refractory cases where oral therapy has failed, given its intravenous administration and risk of infusion reactions. Ultimately, patient‑specific factors drive the selection, and shared decision‑making ensures adherence and optimal outcomes.