Prevention of mercaptopurine-induced hypoglycemia using allopurinol to reduce methylated thiopurine metabolites

Skewing of mercaptopurine (6-MP) metabolism preferentially toward the 6-methylmercaptopurine (6-MMP) metabolite over the antileukemic metabolite 6-thioguanine (6-TGN) is associated with 6-MP-related hepatotoxocity. Allopurinol when coadministered with 6-MP can reduce this skewing and ameliorate the associated adverse effects. The cases we report here demonstrate that aberrant overproduction of 6-MMP is also associated with profound 6-MP-associated hypoglycemia, which can be reversed by administration of allopurinol. This case series contributes to the scant literature on 6-MP-induced hypoglycemia and provides evidence that addition of allopurinol to reduced dose 6-MP can successfully manage this severe toxicity.