Summary

Febuxostat and mercaptopurine have a significant drug interaction that can lead to increased mercaptopurine toxicity. This interaction occurs because febuxostat inhibits xanthine oxidase, an enzyme responsible for metabolizing mercaptopurine, potentially resulting in dangerous accumulation of the chemotherapy drug.

Introduction

Febuxostat (Uloric) is a xanthine oxidase inhibitor primarily used to treat hyperuricemia in patients with gout by reducing uric acid production. Mercaptopurine (6-MP, Purinethol) is a purine analog antimetabolite chemotherapy medication used to treat acute lymphoblastic leukemia, acute myeloid leukemia, and inflammatory bowel disease. Both medications affect purine metabolism pathways, which creates the potential for clinically significant drug interactions.

Mechanism of Interaction

The interaction between febuxostat and mercaptopurine occurs through competitive inhibition of xanthine oxidase. Mercaptopurine is normally metabolized by xanthine oxidase into inactive metabolites, including 6-thiouric acid. When febuxostat inhibits this enzyme, mercaptopurine clearance is significantly reduced, leading to increased plasma concentrations and prolonged exposure. This can result in enhanced therapeutic effects but also increased risk of dose-related toxicities, particularly bone marrow suppression.

Risks and Symptoms

The primary risk of this interaction is severe mercaptopurine toxicity, including life-threatening bone marrow suppression (leukopenia, thrombocytopenia, anemia), gastrointestinal toxicity (nausea, vomiting, diarrhea, mucositis), and hepatotoxicity. Patients may experience increased susceptibility to infections due to immunosuppression. The interaction is considered clinically significant and may require dose adjustments or alternative therapy selection to prevent serious adverse events.

Management and Precautions

If concurrent use is necessary, mercaptopurine doses should be reduced by approximately 75% when used with febuxostat, similar to recommendations for allopurinol co-administration. Close monitoring is essential, including frequent complete blood counts, liver function tests, and clinical assessment for signs of toxicity. Consider alternative uric acid-lowering agents if possible. Patients should be educated about signs of bone marrow suppression and instructed to report fever, unusual bleeding, or signs of infection immediately. Regular communication between oncology and rheumatology teams is crucial for safe management.

Febuxostat interactions with food and lifestyle

Febuxostat can be taken with or without food as food does not significantly affect its absorption. However, patients should limit alcohol consumption while taking febuxostat, as alcohol can increase uric acid levels and counteract the medication's effectiveness in treating gout. Additionally, patients should maintain adequate hydration by drinking plenty of water, as proper hydration helps prevent kidney stone formation and supports the medication's uric acid-lowering effects.

Mercaptopurine interactions with food and lifestyle

Mercaptopurine should be taken on an empty stomach, preferably 1 hour before or 2 hours after meals, as food can significantly reduce absorption and effectiveness. Alcohol consumption should be avoided or limited while taking mercaptopurine, as both the medication and alcohol are processed by the liver, potentially increasing the risk of liver toxicity. Patients should also avoid excessive sun exposure and use appropriate sun protection, as mercaptopurine can increase photosensitivity and skin cancer risk. Additionally, live vaccines should be avoided during treatment due to the immunosuppressive effects of mercaptopurine.