Update to the CPIC Guideline for Thiopurines Regarding Dual TPMT and NUDT15 Intermediate Metabolizers

CPIC has updated guidance for patients who are both TPMT and NUDT15 Intermediate Metabolizers from "Clinical Pharmacogenetics Implementation Consortium Guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update". From the CPIC website:

"At the time of guideline publication, the extent of reduction for thiopurines recommended for patients with intermediate metabolism for both TPMT and NUDT15 was unclear. A recent publication (PMID: 38230823) found that these individuals need a substantial dose reduction to mitigate toxicity in TPMT/NUDT15 IM/IM patients. The recommendation for a TPMT intermediate metabolizer/NUDT15 intermediate metabolizer has been updated for all thiopurines to recommend a starting dose at 20%-50% of normal dosages, depending on the starting dose. See here for updated recommendation tables (azathioprine, mercaptopurine, thioguanine). The pre- and post-test alert tables have been updated accordingly."

Please find the new wording and tables on the PharmGKB guideline annotations for azathioprine, mercaptopurine and thioguanine. The CPIC database and website have also been updated.