Abstract
In October 2023, Japanese health services issued a warning about the risk of hypoglycemia associated with the use
of 6-mercaptopurine（6-MP）in pediatric patients in Japan after several such cases were reported overseas. However, because there are, as of yet, few reports of pediatric hypoglycemia associated with 6-MP therapy in Japan, the veracity of the overseas reports has been called into question. Moreover, no warnings have been issued in Japan about the risks associated with the use of azathioprine, another thiopurine, and it is unclear whether pediatric hypoglycemia is a common adverse effect of this drug class. Based on the Japanese Adverse Drug Event Report database（JADER）, the present study analyzed the relationship between thiopurines and pediatric hypoglycemia using the reporting odds ratio（ROR）and found that the ROR for hypoglycemia caused by thiopurines in all age groups was 0.22（95% confidence interval［CI］: 0.18-0.27）, indicating no significant increase in the hypoglycemia signal. However, when patients receiving thiopurines were stratified into pediatric and adult groups, the ROR for hypoglycemia in the pediatric group was 3.22（95% CI: 2.09–4.97）compared to the adult group, indicating a significantly increased signal. In addition, when the same analysis was conducted separately for 6-MP and azathioprine, the ROR was 15.72（95% CI: 2.07-119.36） and 3.00（95% CI: 1.78-5.05）, respectively, suggesting a significantly increased signal of hypoglycemia. Therefore, 6-MP and other allied drugs, such as azathioprine, should be administered to pediatric patients with due consideration of the possibility of hypoglycemia.
