Thiopurines

Thiopurines & TPMT/NUDT15

Click below to learn more about the use of TPMT and NUDT15 genetics in the prescribing of thiopurines (azathioprine, 6-mercaptopurine, or thioguanine).

Thiopurines, including azathioprine, 6-mercaptopurine (6MP), and thioguanine are metabolized by the liver to inactive metabolites. TPMT and NUDT15, two liver enzymes, are responsible for the majority of the metabolism of thiopurines.

TPMT is a gene that encodes the TPMT liver enzyme. Variation in the TPMT gene results in three TPMT metabolizer phenotypes: normal, intermediate, and poor metabolizers.

NUDT15 is a gene that encodes for the NUDT15 liver enzyme. Variation in the NUDT15 gene results in three NUDT15 metabolizer phenotypes: normal, intermediate, and poor metabolizers.

TPMT and NUDT15 intermediate and poor metabolizer phenotypes are associated with decreased enzyme activity and an increased risk of adverse effects with thiopurines.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a group that evaluates the evidence for the use of pharmacogenetics and then develops clinical practice guidelines. For thiopurines, extensive guideline information can be found at: https://cpicpgx.org/guidelines/guideline-for-thiopurines-and-tpmt/, a reference maintained by CPIC.

Here are three videos that review the CPIC guidelines for thiopurines:

Azathioprine: https://www.youtube.com/watch?v=8Kw0L0wpSBs

6-mercaptopurine (6MP): https://www.youtube.com/watch?v=YQD8lTJw43A

Thioguanine: https://www.youtube.com/watch?v=CN4vocDWdLQ

At UCHealth the use of pharmacogenetics when prescribing thiopurines will occur in patients who meet the following conditions:

1) Provided a blood or saliva sample to the Colorado Center for Personalized Medicine (CCPM) biobank laboratory and this sample has undergone genotyping.
2) Have consented for return of their results.
3) Are prescribed azathioprine, 6-mercaptopurine (6MP), and thioguanine.

This process takes a minimum of 4-6 weeks but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the biobank.

If you are a provider AND your patient has TPMT and/or NUDT15 metabolizer phenotypes available, a best practice advisory (BPA) will warn you in the UCHealth EHR if you attempt to prescribe a thiopurine. If a BPA alerts, clinical guidance, and associated resources will be listed for your reference.

Click here for dosing tips.

Thiopurines Tip Sheets

Webpage updated as of: 4/17/2023

Colorado Center for Personalized Medicine

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Colorado Center for Personalized Medicine (CCPM) Biobank Research Study

15-0461 PI: Casey Greene, PhD: Director, CCPM; Professor and Chair, Department of Biomedical Informatics

Tools & Resources

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Biobank

Colorado Center for Personalized Medicine

Thiopurines & TPMT/NUDT15

Click below to learn more about the use of TPMT and NUDT15 genetics in the prescribing of thiopurines (azathioprine, 6-mercaptopurine, or thioguanine).

Colorado Center for Personalized Medicine

Thiopurines & TPMT/NUDT15

Click below to learn more about the use of TPMT and NUDT15 genetics in the prescribing of thiopurines (azathioprine, 6-mercaptopurine, or thioguanine).

Thiopurines Metabolism and Pharmacogenetics

Clinical Evidence

Clinical Implementation

Further Questions

Colorado Center for Personalized Medicine