Summary

Allopurinol significantly increases capecitabine toxicity by inhibiting dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for metabolizing 5-fluorouracil. This interaction can lead to severe, potentially life-threatening adverse effects and is generally contraindicated.

Introduction

Allopurinol is a xanthine oxidase inhibitor primarily used to treat gout and prevent kidney stones by reducing uric acid production. Capecitabine is an oral fluoropyrimidine chemotherapy agent used to treat various cancers, including colorectal, breast, and gastric cancers. It is converted to 5-fluorouracil (5-FU) in the body, where it interferes with DNA synthesis in cancer cells.

Mechanism of Interaction

The interaction occurs because allopurinol inhibits dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme responsible for metabolizing 5-fluorouracil. When capecitabine is converted to 5-FU in the body, reduced DPD activity leads to decreased clearance and significantly elevated plasma concentrations of 5-FU. This results in prolonged exposure to the active metabolite, dramatically increasing the risk of severe toxicity.

Risks and Symptoms

The primary risk is severe 5-fluorouracil toxicity, which can manifest as life-threatening complications including severe diarrhea, mucositis, neutropenia, thrombocytopenia, and hand-foot syndrome. Patients may experience gastrointestinal toxicity with severe nausea, vomiting, and dehydration. Hematologic toxicity can lead to increased infection risk and bleeding complications. The interaction can also cause severe dermatologic reactions and neurologic toxicity. These effects can be dose-limiting and potentially fatal.

Management and Precautions

Concurrent use of allopurinol and capecitabine is generally contraindicated due to the severity of the interaction. If allopurinol treatment is essential, alternative agents for managing hyperuricemia should be considered, such as febuxostat or probenecid. If both medications must be used, extreme caution is required with significant dose reduction of capecitabine, intensive monitoring for toxicity signs, and frequent laboratory assessments including complete blood counts and liver function tests. Patients should be educated about early toxicity symptoms and instructed to seek immediate medical attention if they occur.

Allopurinol interactions with food and lifestyle

Alcohol consumption should be limited or avoided while taking allopurinol, as alcohol can increase uric acid levels and counteract the medication's effectiveness in treating gout and hyperuricemia. Patients should maintain adequate fluid intake (at least 8-10 glasses of water daily) to help prevent kidney stone formation, which can be a side effect of allopurinol therapy. High-purine foods such as organ meats, anchovies, sardines, and excessive amounts of red meat should be consumed in moderation as part of an overall gout management strategy, though dietary restrictions are less critical when taking allopurinol compared to other gout treatments.

Capecitabine interactions with food and lifestyle

Capecitabine should be taken with food or within 30 minutes after a meal to reduce gastrointestinal side effects and improve absorption. Taking capecitabine on an empty stomach may increase the risk of nausea, vomiting, and diarrhea. Patients should avoid excessive alcohol consumption while taking capecitabine, as alcohol may worsen gastrointestinal side effects and potentially interfere with the drug's metabolism. Additionally, patients should maintain adequate hydration and follow dietary recommendations from their healthcare provider to help manage potential side effects such as hand-foot syndrome and diarrhea.