XO drugs are xanthine oxidase inhibitors, a class of medications that lower uric acid levels in the body. They’re primarily used to treat gout, a painful form of arthritis caused by uric acid crystals building up in the joints. The two most widely prescribed XO inhibitors are allopurinol (the first-line option for decades) and febuxostat, a newer alternative.
If you arrived here looking for a street drug called “XO,” you may be thinking of ecstasy (MDMA), which sometimes goes by “X,” “XTC,” or similar abbreviations. The rest of this article covers the medical class of XO drugs.
How XO Inhibitors Work
Your body naturally breaks down substances called purines, which come from food and from your own cells recycling. An enzyme called xanthine oxidase handles one of the final steps in that breakdown, converting purines into uric acid. Normally, uric acid dissolves in blood, passes through the kidneys, and leaves your body in urine.
When too much uric acid accumulates, it can form sharp, needle-like crystals in joints and surrounding tissue. That’s gout. XO inhibitors block the enzyme responsible for producing uric acid, so less of it enters your bloodstream in the first place. This is different from other gout medications that help your kidneys flush out uric acid faster. XO drugs stop the problem at the source.
Available XO Medications
Only a handful of xanthine oxidase inhibitors are approved for clinical use worldwide.
- Allopurinol is the oldest and most commonly prescribed. It’s a competitive inhibitor, meaning it essentially tricks the enzyme by mimicking the substance the enzyme normally acts on. It’s available as a generic and remains the go-to first choice.
- Febuxostat works differently. It’s a non-competitive inhibitor, blocking the enzyme through a separate mechanism. It’s typically reserved for people who can’t tolerate allopurinol or don’t respond well to it.
- Topiroxostat is a third option approved only in Japan for managing gout and high uric acid levels.
What Treatment Looks Like
If you’re starting allopurinol, expect a gradual process. The typical starting dose is low, and your doctor will increase it every two to five weeks while checking your uric acid levels through blood tests. The goal for people with chronic gout is to bring uric acid below a specific threshold and keep it there long-term. This isn’t a medication you take only during flare-ups. It’s a daily, ongoing treatment designed to prevent future attacks.
People with kidney disease start at an even lower dose, with slower increases. The medication is processed through the kidneys, so reduced kidney function means the drug stays in your system longer and needs more careful management.
One frustrating reality: when you first start an XO inhibitor, gout flares can temporarily get worse. As uric acid levels shift, existing crystals can loosen and trigger inflammation. Your doctor will often prescribe a separate anti-inflammatory medication to cover this transition period, which can last several months.
Serious Side Effects to Know About
Most people tolerate XO inhibitors well, but allopurinol carries a rare and potentially life-threatening risk: a severe allergic skin reaction. This includes conditions where the skin blisters and peels away in sheets, sometimes affecting less than 10% of the body’s surface, sometimes over 30%. These reactions can also involve fever, liver inflammation, and kidney failure.
The risk is strongly tied to a specific genetic variant called HLA-B*58:01. About 7.4% of people with Korean, Han Chinese, or Thai ancestry carry this variant. The rate drops to 3.8% among African Americans and 0.7% among white and Hispanic populations. The American College of Rheumatology recommends genetic testing before starting allopurinol if you’re of Southeast Asian or African American descent. If the test comes back positive, your doctor should choose a different medication.
Heart-Related Concerns With Febuxostat
Febuxostat has its own caution. A large safety trial of over 6,000 gout patients compared febuxostat to allopurinol. The overall rate of major cardiovascular events (heart attacks, strokes, and related emergencies combined) was similar between the two drugs. But when researchers looked at individual outcomes, febuxostat was associated with a higher risk of heart-related death and death from all causes. The FDA requires this warning on the drug’s label, and it’s one reason allopurinol remains the preferred first choice.
Dangerous Drug Interactions
One interaction with allopurinol is genuinely life-threatening. If you’re taking azathioprine or mercaptopurine, two immunosuppressive drugs commonly used after organ transplants or for autoimmune conditions, adding allopurinol can cause severe bone marrow suppression. Your body may stop producing enough white blood cells, red blood cells, or platelets.
Here’s why: those immunosuppressive drugs are normally broken down by the same enzyme that allopurinol blocks. When the enzyme is inhibited, active drug levels surge to dangerous concentrations. If the combination is absolutely necessary, the immunosuppressive dose must be cut to about one-quarter of normal, with frequent blood count monitoring. New Zealand’s medicine safety authority documented 14 cases of this interaction, with 13 resulting in bone marrow suppression.
Uses Beyond Gout
XO inhibitors also play a role in cancer treatment. When chemotherapy destroys large numbers of cancer cells quickly, the cellular debris floods the body with purines, which convert to uric acid. This is called tumor lysis syndrome, and the resulting spike in uric acid can cause acute kidney injury. Allopurinol is started during chemotherapy to prevent this buildup by blocking the enzyme before the uric acid surge begins.
Researchers have also explored the potential cardiovascular benefits of lowering uric acid with XO inhibitors. Allopurinol in particular has shown potential to improve outcomes in patients with heart disease, though this remains an area of active investigation rather than a standard recommendation.