Yes, every category of gout medication carries side effects, though most people tolerate treatment well when doses are introduced gradually and monitored over time. The side effects vary widely depending on whether you’re taking something for an acute flare or a long-term medication to lower uric acid levels. Here’s what to expect from each type.
Anti-Inflammatory Drugs for Flares
When a gout attack hits, the first-line options are NSAIDs (like ibuprofen, naproxen, or indomethacin), colchicine, or short courses of corticosteroids. Each works differently, and each comes with its own set of trade-offs.
NSAIDs at the high doses used for gout flares commonly cause stomach and bowel problems: nausea, diarrhea, and general GI discomfort. Stomach ulcers are a rarer but more serious risk, especially if you use them repeatedly. They’re also unsuitable for people taking blood thinners, those with existing stomach or bowel conditions, or anyone with significant kidney problems.
Colchicine is effective but has a narrow margin between a helpful dose and a toxic one. GI side effects are almost universal at higher doses. In studies of colchicine toxicity, nausea and vomiting occurred in about 90% of cases, abdominal pain in roughly 48%, and diarrhea in about 43%. At prescribed doses for gout, these symptoms are milder, but diarrhea in particular is common enough that many people experience it. Severe colchicine poisoning, though rare at standard doses, can be fatal.
Short courses of corticosteroids (like prednisone) are often used when NSAIDs and colchicine aren’t options. Even brief courses can temporarily raise blood sugar and blood pressure, cause mood changes, and affect sleep. For people with diabetes, the blood sugar spike can be significant enough to require adjustment of their diabetes management during treatment.
Allopurinol: The Most Common Long-Term Drug
Allopurinol is the most widely prescribed medication for lowering uric acid over the long term. For most people, it’s well tolerated. The common side effects are mild: skin rash, occasional GI upset, and sometimes a temporary increase in gout flares when first starting (because shifting uric acid levels can destabilize crystals already in your joints).
The rare but serious concern is allopurinol hypersensitivity syndrome, which affects roughly 1 in 1,000 patients. This reaction can involve severe skin reactions, liver injury, and kidney damage, and it carries a reported mortality rate of 20% to 25%. The risk is nearly 100 times higher in people who carry a specific genetic marker called HLA-B*58:01. This marker is most common in people of Korean descent (about 12%), Han Chinese descent (6% to 8%), and Thai descent (6% to 8%). Current guidelines recommend genetic screening before starting allopurinol if you belong to one of these higher-risk populations. A negative test result makes the risk of this severe reaction very low.
To minimize side effects overall, the standard approach is to start at a low dose (100 mg per day or less, even lower if you have kidney disease) and increase every two to five weeks until your uric acid level drops below 6 mg/dL. This “start low, go slow” method reduces both flare-ups and the chance of a bad reaction.
A Critical Drug Interaction
If you take azathioprine or a related immunosuppressant, allopurinol can cause a dangerous buildup of those drugs in your system. Allopurinol blocks the enzyme that breaks down azathioprine, so the immunosuppressant accumulates to potentially toxic levels. Anyone on azathioprine who needs allopurinol typically has their immunosuppressant dose cut to about 25% of the original. This interaction is serious enough that your prescriber needs to know about all your current medications before you start.
Febuxostat and Heart-Related Risks
Febuxostat works the same way as allopurinol (blocking the enzyme that produces uric acid) and was originally positioned as an alternative. In 2019, the FDA added its strongest warning, a boxed warning, after a clinical trial involving more than 6,000 gout patients revealed an increased risk of heart-related death and death from all causes compared to allopurinol. The overall rate of combined cardiovascular events (heart attack, stroke, unstable chest pain) was similar between the two drugs. But when researchers looked at heart-related deaths specifically, febuxostat performed worse.
As a result, febuxostat is now limited to patients who either don’t respond to allopurinol or can’t tolerate it. If you’re prescribed febuxostat, it typically starts at 40 mg daily or less, with the same gradual dose increases used for allopurinol.
Probenecid and Kidney Stone Risk
Probenecid takes a different approach. Instead of reducing uric acid production, it helps your kidneys flush more uric acid out through urine. The catch is that all that extra uric acid passing through your kidneys can form kidney stones, particularly when you first start the medication. Common side effects include headache, joint pain or swelling, loss of appetite, and nausea.
More concerning signs include blood in the urine, painful urination, or sharp lower back or side pain, which can signal kidney stones or other kidney problems. To reduce this risk, you’ll likely be advised to drink 10 to 12 full glasses of water daily and may be given something to make your urine less acidic. Probenecid is generally not recommended for people with moderate-to-severe kidney disease, where allopurinol or febuxostat are preferred.
Pegloticase for Severe Gout
Pegloticase is an intravenous infusion reserved for people with severe gout that hasn’t responded to other treatments. Its side effect profile is significantly more intense. In clinical trials, 26% of patients receiving infusions every two weeks experienced infusion reactions, ranging from flushing and hives to more serious drops in blood pressure. When given every four weeks, the reaction rate climbed to 41%.
A major challenge with pegloticase is that the body develops antibodies against it. In pre-marketing trials, 92% of patients on the every-two-week schedule developed these antibodies, which can reduce the drug’s effectiveness and increase infusion reactions. Combining pegloticase with methotrexate (an immune-modulating drug) brought the infusion reaction rate down to about 4% and cut antibody development roughly in half, which is why this combination approach has become more standard.
What Monitoring Looks Like
If you’re on long-term uric acid-lowering therapy, expect regular blood tests. Your uric acid level is checked after each dose adjustment to make sure you’re reaching the target of below 6 mg/dL. Kidney and liver function are also monitored, since the two most common long-term medications (allopurinol and febuxostat) are processed through these organs. This ongoing monitoring is how your prescriber catches problems early, before side effects become serious.
One thing that catches many people off guard: when you first start a uric acid-lowering medication, you may actually get more gout flares for several weeks or months. This isn’t a sign the medication is failing. It happens because lowering uric acid levels causes existing crystals in your joints to dissolve and shift, temporarily triggering inflammation. Most treatment plans include a low-dose anti-inflammatory (often colchicine) during this transition period to prevent or soften these flares.