What Drugs Should Not Be Taken with Febuxostat? Essential Safety Information

October 14, 2025 •

3 min read

Serious, and even fatal, bone marrow suppression can occur when febuxostat is taken with immunosuppressant drugs like azathioprine and mercaptopurine. Understanding what drugs should not be taken with febuxostat is critical for safe gout management.

Quick Summary

This article details the major drug contraindications and potential interactions associated with febuxostat, highlighting crucial safety precautions regarding immunosuppressants, theophylline, and other medications.

Key Points

Absolute Contraindications: Febuxostat should never be taken with the immunosuppressants azathioprine or mercaptopurine due to a severe risk of fatal bone marrow suppression.
Mechanism of Interaction: The danger arises because febuxostat inhibits xanthine oxidase, an enzyme vital for metabolizing azathioprine and mercaptopurine, causing toxic buildup.
Caution with Theophylline: Co-administration with theophylline is not advised without extreme caution, as febuxostat affects its metabolism, creating a metabolite with unknown long-term safety.
Monitoring with Rosuvastatin: Taking febuxostat with rosuvastatin can increase statin levels, elevating the risk of muscle and liver issues, requiring potential dose adjustments and close monitoring.
FDA Boxed Warning: Febuxostat carries a boxed warning from the FDA for an increased risk of cardiovascular death compared to allopurinol, especially in patients with pre-existing heart disease.
Inform Your Doctor: Always provide your doctor with a complete list of all medications, supplements, and OTC drugs to prevent harmful interactions.

Febuxostat is an oral medication for managing chronic hyperuricemia in adults with gout. It is a xanthine oxidase inhibitor, blocking the enzyme that produces uric acid. While effective for gout, its mechanism can lead to dangerous interactions with drugs metabolized by the same enzyme. Understanding these interactions is vital for safe treatment.

Absolute Contraindications: Immunosuppressants

The most critical interaction involves febuxostat with azathioprine and mercaptopurine. These combinations are absolutely contraindicated, meaning they must never be used together.

Azathioprine

Azathioprine is used for autoimmune conditions and transplant rejection. It converts to active metabolites like 6-mercaptopurine. Febuxostat inhibits xanthine oxidase, essential for azathioprine's metabolism, leading to toxic buildup of these metabolites. This can cause severe, life-threatening bone marrow suppression (myelosuppression).

Mercaptopurine

Mercaptopurine (6-MP) treats certain cancers and immune disorders. Its metabolism also relies on xanthine oxidase. Febuxostat prevents its breakdown, significantly increasing mercaptopurine levels. This can cause severe toxicities, including bone marrow suppression, which is why co-administration is strictly prohibited.

Other Clinically Significant Interactions

Other drugs require caution due to potential risks.

Theophylline

Theophylline, a bronchodilator for respiratory issues, is also metabolized by xanthine oxidase. While short-term studies didn't show significant changes in theophylline levels with febuxostat, they did show a rise in a metabolite (1-methylxanthine). The long-term safety of this metabolite is unknown, so caution is advised, with some sources listing it as contraindicated.

Didanosine

Didanosine, an HIV medication, can also be affected by xanthine oxidase inhibitors. Taking it with febuxostat can increase didanosine levels, raising the risk of side effects like pancreatitis. Some sources consider this combination contraindicated.

Rosuvastatin

Febuxostat can increase levels of the cholesterol-lowering drug rosuvastatin. This increases the risk of statin side effects like liver damage and rhabdomyolysis. Dose adjustments or increased monitoring may be needed.

FDA Boxed Warning for Cardiovascular Risk

Febuxostat has a boxed warning due to an increased risk of cardiovascular-related death in patients with established cardiovascular disease compared to allopurinol. The FDA restricts febuxostat use to patients who cannot take or tolerate allopurinol. Patients with a history of heart problems should discuss risks with their doctor.

Comparison of Key Febuxostat Interactions


Drug Class	Examples	Interaction Severity	Mechanism	Required Action
Immunosuppressants	Azathioprine, Mercaptopurine	Severe; Contraindicated	Febuxostat inhibits xanthine oxidase, leading to dangerous accumulation of active drug metabolites.	Must not be taken together; alternative therapies must be used.
Xanthine Substrates	Theophylline, Didanosine	Moderate to Severe	Inhibition of xanthine oxidase affects drug metabolism and increases levels of metabolites or the parent drug.	{Link: DailyMed dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b94994e0-cdb5-42cc-bc3c-75154e87561d&audience=consumer} use with caution or avoid; monitor closely for toxicity with theophylline. Didanosine is often contraindicated.
Statins	Rosuvastatin	Moderate	Febuxostat significantly increases blood levels of rosuvastatin.	Dose adjustment and increased monitoring are necessary to mitigate risks of side effects like rhabdomyolysis.

Conclusion: Prioritizing Patient Safety

Febuxostat is an effective gout treatment, but its potential for severe drug interactions and cardiovascular risks requires careful consideration. The most crucial interaction is with azathioprine and mercaptopurine, which are absolutely contraindicated due to fatal toxicity risks. Caution is also needed with drugs like theophylline and rosuvastatin. Always inform your healthcare provider of all medications and supplements. Patients with cardiovascular conditions should discuss the boxed warning with their doctor. {Link: DailyMed dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b94994e0-cdb5-42cc-bc3c-75154e87561d&audience=consumer} Knowledge of these interactions is key to safe gout management.

For more information on the cardiovascular risk associated with this medication, refer to the FDA Drug Safety Communication.

Frequently Asked Questions

Febuxostat is a xanthine oxidase inhibitor, meaning it blocks an enzyme (xanthine oxidase) that your body uses to break down azathioprine and mercaptopurine. Taking them together causes a dangerous buildup of these drugs, which can lead to severe and potentially fatal bone marrow suppression.

The combination should be used with caution, and in some cases, is contraindicated. Febuxostat affects theophylline's metabolism, producing a metabolite with unknown long-term safety. It is best to consult your doctor for guidance and potential monitoring.

Febuxostat can increase the blood concentration of rosuvastatin, raising the risk of severe side effects like liver damage and a muscle breakdown condition called rhabdomyolysis. Your doctor may need to adjust your rosuvastatin dose or monitor you more frequently.

Febuxostat carries an FDA boxed warning for an increased risk of cardiovascular-related death in patients with a history of cardiovascular disease. Its use is generally reserved for patients who cannot take or tolerate allopurinol, and the risks should be carefully weighed against the benefits with a healthcare professional.

Febuxostat can be taken with or without food. However, it is recommended to limit alcohol consumption, as alcohol can increase uric acid levels and counteract the medication's effectiveness.

If you suspect you have taken a contraindicated drug like azathioprine or mercaptopurine with febuxostat, you should seek immediate medical attention. Be aware of symptoms like severe weakness, unusual bruising, fever, or signs of infection.

Yes, other medications like the antiretroviral drug didanosine may also interact. You should inform your healthcare provider about all prescription and over-the-counter medicines, vitamins, and herbal products you are taking to ensure no harmful interactions occur.