Allopurinol vs Alternatives: What Works Best for Gout and High Uric Acid?

If you’re taking allopurinol for gout or high uric acid, you’ve probably wondered: is there something better? Maybe your joints still flare up. Maybe you got a rash. Or your doctor just said, ‘Let’s try something else.’ You’re not alone. Thousands of people on allopurinol switch every year-not because it doesn’t work, but because it doesn’t work for them.

What allopurinol actually does

Allopurinol is a xanthine oxidase inhibitor. That’s a fancy way of saying it blocks the enzyme that turns purines into uric acid. When you eat red meat, seafood, or drink beer, your body breaks down purines. If your body makes too much uric acid-or can’t flush it out-it builds up, forms sharp crystals in your joints, and triggers painful gout attacks. Allopurinol cuts that production by 70-80% in most people. It’s been around since the 1960s. It’s cheap. It’s in guidelines everywhere. But it’s not perfect.

Why people stop taking allopurinol

Three main reasons show up in patient surveys and clinical studies:

• Side effects: Skin rashes (1-5% of users), sometimes severe like Stevens-Johnson syndrome
• Ineffectiveness: 20-30% of people don’t reach target uric acid levels (< 6 mg/dL) even on high doses
• Drug interactions: Especially with azathioprine or mercaptopurine-can be dangerous

A 2023 UK study of 1,200 gout patients found that 41% had switched off allopurinol within three years. Most didn’t quit because they felt better-they quit because they couldn’t tolerate it.

Febuxostat: The most common alternative

Febuxostat (brand name Uloric) works the same way as allopurinol-blocks xanthine oxidase-but it’s chemically different. That matters. People who can’t take allopurinol often handle febuxostat just fine.

Studies show febuxostat lowers uric acid more effectively than standard doses of allopurinol. In one trial, 62% of patients on 40 mg febuxostat hit their target uric acid level, compared to 42% on 300 mg allopurinol. It’s also not broken down by the liver the same way, so it’s safer for people with mild kidney issues.

But it’s not risk-free. The FDA added a black box warning in 2019 after a study showed a slightly higher risk of heart-related death. That doesn’t mean everyone should avoid it-but if you have heart disease, your doctor should weigh the pros and cons carefully. It’s also more expensive. A 30-day supply in the UK costs about £35-£45, while allopurinol is under £5.

Probenecid: The ‘flush it out’ option

Probenecid doesn’t stop your body from making uric acid. Instead, it tells your kidneys to pee it out faster. It’s ideal if your body makes a normal amount of uric acid but just can’t clear it-common in younger patients or those with mild kidney function.

It’s been used since the 1950s. It’s cheap. It’s gentle on the liver. But it needs you to drink a lot of water-up to 2 litres a day-or you risk kidney stones. It also doesn’t work well if your kidneys are already damaged (eGFR under 50). And it interacts with aspirin, NSAIDs, and some antibiotics.

It’s not first-line anymore, but for the right person, it’s a solid, low-risk option. Many patients on probenecid report fewer side effects than on allopurinol.

Lesinurad: The combo player

Lesinurad (Zurampic) is almost never used alone. It’s only approved to be taken with allopurinol or febuxostat. It boosts how well your kidneys clear uric acid. Think of it as a sidekick for the main drug.

It’s useful if you’re on allopurinol but your uric acid stays above 6 mg/dL. In trials, adding lesinurad pushed another 30-40% of patients into target range. But it comes with a catch: it raises the risk of kidney problems. You need regular blood tests. And it’s expensive-£120+ per month in the UK.

Most GPs won’t prescribe it unless you’ve tried everything else. It’s a niche tool, not a first choice.

Pegloticase: For the toughest cases

If you’ve tried allopurinol, febuxostat, probenecid, and even lesinurad-and you still get frequent gout attacks or tophi (those lumpy uric acid deposits under your skin)-then pegloticase might be the answer.

This is an IV infusion given every two weeks. It doesn’t just lower uric acid-it breaks down existing crystals. In trials, 45% of patients saw complete resolution of tophi after six months. That’s life-changing for people who’ve struggled for years.

But it’s not simple. You need to be monitored for allergic reactions. It’s given in a clinic, not at home. And it costs over £10,000 a year in the UK. It’s reserved for severe, treatment-resistant gout. Only about 1 in 50 gout patients ever get here.

Comparison table: Allopurinol vs alternatives

Who should switch from allopurinol?

You might need a change if:

• You’ve had a skin rash or blistering after taking it
• Your uric acid is still above 6 mg/dL after 3 months on 300 mg daily
• You’re on azathioprine for an autoimmune disease
• You have moderate to severe kidney disease and need something gentler
• You’re young and your body clears uric acid poorly (probenecid may suit you better)

Don’t stop allopurinol on your own. Stopping suddenly can trigger a gout flare. Always work with your doctor to taper and switch safely.

What about natural options?

Cherry juice? Vitamin C? Coffee? Some studies show small, modest drops in uric acid-maybe 1-2 mg/dL. That’s not enough to control gout on its own. They might help as extras, but they’re not replacements for medication. If you’re relying on supplements instead of proven drugs, you’re risking joint damage and long-term complications.

Final thoughts: It’s not about the best drug-it’s about the right one

There’s no single ‘best’ uric acid reducer. Allopurinol is the starting point because it’s safe, cheap, and effective for most. But medicine isn’t one-size-fits-all. Your age, kidney health, heart history, diet, and even your genes matter.

For someone with mild gout and healthy kidneys, allopurinol is still the gold standard. For someone with heart disease and poor response, febuxostat might be better. For a young patient with normal production but poor clearance, probenecid could be ideal. And for the rare few with stubborn tophi, pegloticase can be a miracle.

The goal isn’t just to lower uric acid-it’s to stop the pain, protect your joints, and keep you moving. That means finding the drug that fits you, not just the one on the guideline.

Next steps if you’re considering a switch

Start by asking your doctor for a uric acid blood test if you haven’t had one in the last 3 months. If it’s above 6 mg/dL, you’re still at risk. Then ask: “Based on my history, could another drug work better?” Bring a list of your side effects, your lifestyle, and your goals. Are you trying to avoid infusions? Reduce costs? Prevent joint damage? Your answers will guide the choice.

Don’t wait until your next flare. Gout isn’t just about pain-it’s about protecting your bones, kidneys, and heart. The right drug can change that.