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

Allopurinol is generally well-tolerated and is one of the most commonly prescribed long-term medications in the United States. But like all medications, it can cause side effects — ranging from mild and manageable to rare but serious. Knowing what to watch for can help you catch problems early and get the most benefit from your treatment.

Common Side Effects of Allopurinol

Most people tolerate allopurinol well. The most commonly reported side effects (occurring in more than 1% of patients) include:

• Nausea: The most commonly reported GI side effect. Taking allopurinol with food or after a meal significantly reduces nausea in most patients.
• Diarrhea: Less common than nausea but reported in some patients. Usually mild and improves with time.
• Elevated liver enzymes (liver function tests): Mild, transient elevations are seen in some patients and usually return to normal. Severe hepatotoxicity is rare.
• Mild skin rash: A mild rash is relatively common (reported in about 2% of patients). However, any rash should be reported to your doctor immediately — a mild rash can be an early warning sign of a more serious reaction.
• Drowsiness or dizziness: Some patients report mild drowsiness or dizziness. Use caution when driving until you know how allopurinol affects you.

Gout Flares During Early Treatment — Why Do They Happen?

One of the most confusing aspects of starting allopurinol is that it can actually trigger gout attacks during the first few weeks to months of therapy — even as uric acid levels fall. This happens because as allopurinol lowers serum uric acid, crystals that have accumulated in joints and soft tissue begin to dissolve and mobilize, which can trigger inflammation.

This is completely expected and does NOT mean the medication isn't working. Your doctor will often prescribe a short course of colchicine or a low-dose NSAID to take alongside allopurinol for the first 3–6 months to prevent these flares. If you experience a flare while on allopurinol, do not stop taking allopurinol — contact your doctor about managing the flare.

Serious Side Effects — Stop Taking Allopurinol and Call Your Doctor Immediately

Allopurinol has been associated with rare but potentially life-threatening reactions. Discontinue allopurinol immediately and seek medical care if you develop any of the following:

• Skin rash (any kind): Stop allopurinol at the first appearance of a rash, no matter how mild. Rash can be an early warning of Stevens-Johnson syndrome (SJS) or DRESS syndrome.
• Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN): A life-threatening skin reaction. Signs include spreading rash with blistering, peeling skin, painful sores in the mouth or eyes, and fever. Call 911 immediately.
• DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms): Fever, widespread rash, swollen lymph nodes, and elevated blood counts. Can affect multiple organs. Requires emergency care.
• Signs of liver problems: Yellowing of skin or eyes (jaundice), dark urine, clay-colored stools, upper right abdominal pain.
• Signs of blood problems (myelosuppression): Unusual bruising or bleeding, persistent fatigue, fever without apparent cause, or unusual susceptibility to infections.
• Signs of kidney problems: Painful urination, blood in urine, decreased urine output, significant swelling.

The HLA-B*5801 Genetic Risk Factor

Patients with the HLA-B*5801 genetic variant have a dramatically higher risk of developing severe skin reactions (SJS/TEN) from allopurinol. This variant is found in approximately 6–8% of Han Chinese, Thai, and Vietnamese individuals, and about 4% of African Americans. If you are of Southeast Asian or African American descent, ask your doctor about HLA-B*5801 genetic testing before starting allopurinol.

How to Minimize Side Effects

1. Take with food: Reduces nausea significantly.
2. Drink plenty of water: Aim for 8–10 glasses of fluid per day to support kidney function and reduce kidney stone risk.
3. Start low, go slow: Your doctor will typically start at 100 mg and increase gradually — this reduces the risk of gout flares and hypersensitivity reactions.
4. Tell your doctor about ALL medications: Several drugs interact dangerously with allopurinol, including azathioprine, warfarin, and some antibiotics.

For a full review of drug interactions, see our guide on allopurinol drug interactions: what to avoid and what to tell your doctor.