Allopurinol Side Effects: What to Expect and When to Call Your Doctor

If your doctor has prescribed allopurinol to manage gout or high uric acid levels, it helps to know what to expect before you start. Allopurinol side effects are usually mild — nausea, diarrhea, and a gout flare shortly after starting are the most common — but there’s one serious, rash-related reaction that every patient on this medication should be able to recognize right away. Here’s what the FDA prescribing information shows about allopurinol’s common and serious side effects, including who faces a higher risk of the rare but dangerous reactions.

What Allopurinol Is Used For

Allopurinol lowers the amount of uric acid the body produces, and it’s prescribed for several related conditions. The most common use is gout, both to prevent future flares in people who’ve had recurrent attacks and to treat the uric acid buildup (tophi) and joint damage that can come with long-standing, poorly controlled gout. It’s also used in people undergoing certain cancer treatments, where rapidly dying tumor cells can release a surge of uric acid into the bloodstream, and in people who form recurrent calcium oxalate kidney stones linked to high uric acid excretion. According to the FDA label, allopurinol isn’t recommended for simply having a high uric acid level on a blood test without any symptoms, since the medication carries real risks that should be weighed against an actual clinical problem, not just a number.

Common Side Effects

Based on FDA prescribing information, the adverse reactions reported in more than 1% of patients taking allopurinol include:

• Skin rash. Described in the FDA label as the single most frequent adverse reaction, usually a mild, raised (maculopapular) rash — but see below for why any rash needs immediate attention regardless of how mild it looks.
• Nausea and diarrhea. Digestive upset is common, especially when starting the medication, and often improves by taking it with food.
• Increases in liver function test results. Including AST, ALT, and alkaline phosphatase, usually mild and found on routine blood work rather than through any symptom.
• Acute gout flares. Somewhat counterintuitively, starting allopurinol can trigger a gout flare in the first weeks of treatment, discussed in more detail below.
• Drowsiness, somnolence, or dizziness. Reported in the FDA label without a specific frequency given, but worth noting if you drive or operate machinery.

Most of these effects are manageable and don’t require stopping the medication, though any new or worsening rash is the one exception — that always warrants stopping allopurinol and contacting your doctor right away, discussed in detail in the next section.

The Rash Warning: Why It’s Different From an Ordinary Drug Rash

This is the single most important safety point for anyone taking allopurinol. The FDA label instructs patients and doctors to discontinue allopurinol permanently at the very first appearance of a skin rash, rather than waiting to see if it gets worse or trying an antihistamine first. That’s because a rash can be the earliest warning sign of a group of rare but severe reactions — including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and a condition called DRESS (drug reaction with eosinophilia and systemic symptoms) — that together occur in roughly 5 in 10,000 patients (about 0.05%) according to the FDA label. These reactions can cause widespread skin blistering and peeling, organ involvement, and can be life-threatening, which is why the standard advice for an ordinary medication rash (wait and see) doesn’t apply here. If you develop any rash while taking allopurinol, stop the medication and contact your doctor the same day, rather than waiting for your next scheduled appointment.

Who Faces a Higher Genetic Risk

A specific genetic variant, HLA-B*58:01, substantially raises the risk of these severe rash-related reactions, and how common this gene variant is varies a great deal by ancestry. According to the FDA label, it’s found in about 8% to 10% of people of Han Chinese descent, about 8% of people of Thai descent, about 6% of people of Korean descent, about 4% of Black patients, roughly 1% to 2% of Hispanic and Indigenous American patients, and under 1% of patients of European or Japanese descent. The FDA label states that allopurinol use is not recommended in patients who test positive for HLA-B*58:01 unless the benefits clearly outweigh the risks, and that genetic testing may be worth considering before starting allopurinol in populations where the variant is more common. Importantly, the FDA also notes that these severe reactions can still occur in people who test negative for the gene variant, regardless of ethnic background, so a negative test doesn’t eliminate the need to watch for a rash.

Why Starting Allopurinol Can Trigger a Gout Flare

It can seem backward that a medication meant to treat gout might trigger a flare right after you start it, but this is a well-documented, expected effect. As uric acid levels begin to fall, crystals that have built up in and around the joints over time start to break down and get reabsorbed, and this process itself can provoke inflammation and an acute flare. The FDA label notes that starting at a low dose and increasing it gradually — typically beginning around 100 mg daily and raising it by 100 mg increments no more than once a week until uric acid reaches a target level — helps reduce the risk of both flares and serious adverse reactions. Many doctors also prescribe a short course of colchicine or an anti-inflammatory medication for the first few months of allopurinol treatment specifically to prevent these flares. Importantly, the FDA label notes that if a flare does happen while you’re on allopurinol, the medication doesn’t need to be stopped — the flare is treated on its own while allopurinol continues working to lower uric acid long-term.

Drug Interactions Worth Knowing About

• Azathioprine and mercaptopurine. Allopurinol significantly slows how the body breaks down these immune-suppressing medications, so the FDA label calls for reducing their dose to roughly one-quarter to one-third of the usual amount when combined with allopurinol, to avoid toxicity.
• Warfarin. Allopurinol may enhance warfarin’s blood-thinning effect, so more frequent monitoring of your INR (a blood clotting measurement) is typically recommended after starting or stopping allopurinol.
• Thiazide diuretics and certain antibiotics. The FDA label notes that thiazide diuretics and the antibiotics ampicillin or amoxicillin can raise the risk of rash when combined with allopurinol, and thiazides may also require a dose adjustment in people with reduced kidney function.

Because allopurinol interacts meaningfully with several common medications, it’s worth making sure your doctor and pharmacist have a complete, current list of everything you take, including over-the-counter products, before starting.

Kidney Function and Dosing

Allopurinol is cleared from the body by the kidneys, so the FDA label includes specific dose reductions for people with reduced kidney function, ranging from no adjustment needed at normal kidney function down to a much lower dose, taken less frequently, for severely reduced kidney function or those on dialysis. This is one more reason it’s important to have kidney function checked before starting allopurinol and periodically afterward, since dosing that’s appropriate for someone with normal kidney function could build up to higher, riskier levels in someone whose kidneys clear it more slowly.

Connecting This to Other Gout Treatments

Allopurinol is usually a long-term, daily medication aimed at preventing future gout flares by keeping uric acid low, which is different from medications used to treat pain and inflammation during an active flare. NSAIDs such as naproxen or ibuprofen, and sometimes a cortisone injection, are commonly used for the acute pain of a flare itself, often alongside allopurinol rather than instead of it. Understanding this distinction — one medication for long-term prevention, another for short-term flare relief — helps explain why your doctor may have you taking more than one gout-related medication at different points in your treatment.

Tips for Taking Allopurinol Safely

• Stop and call your doctor immediately at the first sign of any rash. This is the one symptom that should never be watched and waited on.
• Take it with food if it upsets your stomach. This often helps with the nausea some people experience when starting.
• Don’t stop allopurinol on your own if a gout flare occurs after starting it. This is an expected, treatable effect, not a sign the medication isn’t working.
• Tell your doctor about every other medication you take. Especially azathioprine, mercaptopurine, warfarin, or a thiazide diuretic.
• Stay well hydrated. Adequate fluid intake supports kidney function and uric acid clearance.
• Keep up with recommended blood tests. Including kidney function, liver function, and uric acid level, especially in the first few months of treatment.

When to Call Your Doctor

Call your doctor promptly for persistent nausea, diarrhea that doesn’t improve, or a gout flare that feels severe or doesn’t respond to your usual flare treatment. Stop allopurinol and seek medical attention immediately for any new rash, especially one involving blistering, peeling skin, mouth sores, fever, or swelling of the face, since these can be early signs of a serious reaction that needs urgent evaluation.

Frequently Asked Questions

Why did I get a gout flare after starting allopurinol?

This is a known, expected effect in the first weeks of treatment, caused by uric acid crystals breaking down and being reabsorbed as levels fall. It doesn’t mean the medication isn’t working, and many doctors prescribe a short course of colchicine or an anti-inflammatory to help prevent it.

Should I stop taking allopurinol if I develop a rash?

Yes — the FDA label specifically advises discontinuing allopurinol permanently at the first appearance of any rash and contacting your doctor right away, since a rash can be the earliest sign of a rare but serious reaction.

Do I need a genetic test before starting allopurinol?

It depends on your background. The FDA label notes that testing for the HLA-B*58:01 gene variant may be worth considering in populations where it’s more common, including people of Han Chinese, Thai, or Korean descent. Ask your doctor whether testing makes sense for you.

Can I take ibuprofen or naproxen while on allopurinol?

Generally, yes — NSAIDs are commonly used together with allopurinol, particularly during an acute gout flare, since they work differently and treat different things (short-term inflammation versus long-term uric acid control). Confirm with your doctor based on your full health picture, including kidney function.

How long does it take for allopurinol to lower uric acid?

Uric acid levels typically begin dropping within the first few weeks, but reaching a stable target level often takes gradual dose increases over several weeks to months, following the FDA-recommended titration schedule of increasing by 100 mg no more than once a week.

This article is for general educational purposes and isn’t a substitute for personalized medical advice. Never start, stop, or change a prescription medication without talking to your doctor first.

Allopurinol’s everyday side effects — nausea, a gout flare when starting, mild liver test changes — are common and generally manageable with guidance from your doctor. The one rule that matters most is simple: any new rash means stopping the medication and calling your doctor immediately, since that single symptom is how the rare but serious reactions first show up. Staying on top of recommended blood tests and keeping your doctor informed of every medication you take rounds out the safety picture for this long-term gout treatment.