Allopurinol for mercaptopurine (6-MP) toxicity

Mercaptopurine is a critical component of maintenance therapy. Most patients tolerate the recommended doses of mercaptopurine with minimal side effects such as mild transaminitis and facial rashes. However, some patients experience more severe side effects, including liver toxicity, fasting hypoglycemia, abdominal pain, and fatigue. Mercaptopurine is metabolized to 6-thioguanine (6-TGN), which is responsible for its antileukemic effect, and also to 6-methylmercaptopurine nucleotides (6-MMP), which can be hepatotoxic. Allopurinol inhibits xanthine oxidase and blocks the conversion of mercaptopurine into 6-MMP via inhibition of TPMT. This results in increased production of 6-TGN and decreased 6-MMP. In several small, retrospective, single-center studies, the use of allopurinol in patients with ALL in maintenance decreased nonhematologic toxicity of mercaptopurine, especially hepatotoxicity and other GI-related side effects. Because an increase in 6-TGN metabolites is associated with myelosuppression, concurrent use of allopurinol with mercaptopurine typically requires a lower dose of mercaptopurine to avoid excessive neutropenia and thrombocytopenia.[132-135]