Allopurinol vs. Febuxostat for Gout Prevention

As you get older, you might notice some joint stiffness or discomfort from arthritis. But for millions of people in the U.S., arthritis pain can be due to painful gout flares. Joint pain and swelling from a gout flare can last for days or weeks.

In general, gout is the result of uric acid build-up that crystallizes (settles) in certain joints, like in your big toe. This can lead to a sudden feeling of intense pain, commonly known as a gout flare. When a gout flare hits, pain and discomfort hinder your quality of life. 

Thankfully, medications are available that can help treat or prevent your symptoms. Two common preventative options are called allopurinol (Zyloprim) and febuxostat (Uloric).

In this article, we will compare allopurinol and febuxostat — what they are, how effective they are, and side effects you can expect.

How do xanthine oxidase inhibitors work for gout?

Gout is caused by high amounts of uric acid, which are made from purines. Purines are naturally-occurring chemicals in your body. You can also find this chemical in high amounts in some foods and drinks — like sardines and beer. 

To convert purines into uric acid, the body uses a protein called xanthine oxidase. By blocking this protein, xanthine oxidase inhibitor (XOI) medications stop your body from making more uric acid from purines. This helps prevent future gout attacks. 

What is allopurinol?

Allopurinol is a prescription medication that’s taken by mouth. As a XOI, allopurinol works by lowering the amount of uric acid in your body. 

What other conditions is allopurinol approved to treat?

In addition to gout, allopurinol is FDA-approved for several health conditions, including:

Tumor lysis syndrome 

This is a condition that affects certain people with cancer. As cancer cells die, they can release their inner contents into your body. This may lead to significant changes in salts and chemicals — like uric acid — in your body. These changes can be excessive and result in heart, kidney, and liver damage. This is a medical emergency called tumor lysis syndrome (TLS), and it’s usually caused by chemotherapy treatments.

Kidney stones due to high uric acid amounts in the urine 

People with high amounts of uric acid in their urine — more than 750 mg/day in women or 800 mg/day in men — are more likely to have kidney stones. 

By lowering the amount of uric acid in your body, allopurinol can help prevent these conditions. 

What is febuxostat?

Like allopurinol, febuxostat is a prescription medication taken by mouth. Febuxostat is also an XOI, so it works the same way as allopurinol. It’s considered to be an alternative option to allopurinol for gout. 

What conditions is febuxostat approved to treat?

Unlike allopurinol, febuxostat is only approved for gout prevention. It’s not approved to treat or prevent any other health conditions. Also, febuxostat should only be used for gout in certain situations:

• Allopurinol didn’t work for you: If allopurinol can’t lower your uric acid level to less than 6 mg/dL, then experts recommend switching to another medication — like febuxostat.

• Allopurinol causes intolerable side effects: If you have bothersome side effects from allopurinol, then febuxostat might be another option for you.

• Allopurinol isn’t safe for you: If you experienced a severe allergic reaction with allopurinol, then febuxostat is a potential option to try instead. Some people — like those of Southeast Asian or African American descent — might have a higher risk of this serious side effect. You can receive a genetic test from your healthcare provider to see if you have a genetic change that raises the likelihood of this severe reaction.

How are allopurinol and febuxostat dosed and given?

The following table provides information on how allopurinol and febuxostat are dosed and given for gout.

As a reminder, allopurinol is approved for uses other than gout. If you have questions about how allopurinol is used for other medical conditions, talk with your healthcare provider.

How effective are allopurinol and febuxostat for gout?

In addition to changes in your symptoms over time, blood work helps determine how effective these medications are. If a medication can lower your uric acid levels to less than 6 mg/dL, then experts typically consider it effective for gout. 

Both medications are effective options. In a key study that helped lead to febuxostat’s approval, it was shown that both allopurinol and febuxostat can help people achieve a uric acid level of below 6 mg/dL. Febuxostat helps more people achieve ideal uric acid levels, but it also has more risks. More on this next. 

What are the known side effects of allopurinol and febuxostat?

Both medications have a number of possible side effects. The following are some common side effects of allopurinol and febuxostat.

What are the serious side effects of allopurinol and febuxostat?

Although less common than the side effects mentioned above, serious side effects are possible with allopurinol or febuxostat.

Heart-related effects

Another key study found that febuxostat is linked to a higher risk of heart-related deaths than allopurinol. As a result, experts recommend allopurinol over febuxostat — especially for people with the following:

• Heart disease due to atherosclerosis (hardening of the arteries)

• History of a heart attack

• History of a stroke

• History of unstable angina (chest pain)

However, more recent studies suggest that febuxostat’s potential heart-related risks may not be as high as originally thought. Many health experts believe that these risks are less severe and comparable to those of allopurinol. This relationship is still being studied.

Gout attacks

Gout attacks tend to happen if you’re new to taking allopurinol or febuxostat. These can happen while your body is still getting used to the medication.

To prevent this side effect, healthcare providers slowly raise your XOI dose in the beginning. Experts also recommend an additional treatment with one of the following medications to relieve inflammation (swelling) for at least 3 to 6 months.

• Colchicine (Colcrys, Mitigare)

• Corticosteroids, like prednisone

• Nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen (Advil, Motrin) 

Rash

A rash can be a symptom of a severe allergic reaction to allopurinol or febuxostat. If you experience a skin rash, stop taking the XOI and get medical help right away.

Liver failure

There are reports of liver problems with both allopurinol and febuxostat. Immediately seek medical attention if you notice the following symptoms of liver damage:

• Dark-colored urine

• Nausea and vomiting

• Upper right-sided stomach pain

• Yellow-colored skin and eyes (jaundice)

What interactions do allopurinol and febuxostat have?

In general, don’t take allopurinol or febuxostat with azathioprine (Imuran) or mercaptopurine. 

Azathioprine is typically used for rheumatoid arthritis (RA) or after a kidney transplant. Mercaptopurine is usually used with other medications for acute lymphoblastic leukemia (ALL) — a type of blood cancer.

XOIs can lead to high amounts of azathioprine or mercaptopurine in the body, which can lead to a higher likelihood of side effects. If combining these medications with an XOI is necessary, then your healthcare provider will lower the dose of these medications and closely monitor for side effects.

These are two key interactions, but this is not a complete list of interactions for allopurinol and febuxostat. For more information about medication interactions for each XOI, talk to your pharmacist or healthcare provider.

Can you take allopurinol and febuxostat together?

Since allopurinol and febuxostat work the same way, they shouldn’t be taken together. If an XOI doesn’t work, experts usually recommend switching from one to the other. 

But if combination therapy is necessary to help control your gout symptoms, experts may recommend combining allopurinol with an uricosuric — like probenecid. Uricosuric medications work by eliminating more uric acid through the urine.

How to save on allopurinol and febuxostat

Allopurinol and febuxostat are both available as lower-cost generics. GoodRx can help you navigate the many ways to save on your prescription.

• Save with GoodRx. GoodRx can help you save over 70% off the average retail price of the generic versions of allopurinol and febuxostat. Generic allopurinol’s price at certain pharmacies is less than $13.16 with a free GoodRx discount. Generic febuxostat’s price at certain pharmacies is less than $43.60 with a free GoodRx discount.

• Save with patient assistance programs. If you’re uninsured or underinsured, you may be eligible for the allopurinol or febuxostat patient assistance programs, which offer the medications at no charge.

How do healthcare providers decide which medication to prescribe?

Experts usually recommend allopurinol as the first choice medication for gout — especially in people with heart concerns. Compared to febuxostat, allopurinol is also typically less expensive and has more possible uses.

But allopurinol isn’t right for everyone. Talk to your healthcare provider to find out which medication may be best for you.

Why trust our experts?

Written by:

Ross Phan, PharmD, BCACP, BCGP, BCPS

Ross Phan is a board-certified clinical pharmacist. She has roughly two decades of healthcare experience — with most of her experience being pharmacy related.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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