Annotation of CPIC Guideline for mercaptopurine and NUDT15, TPMT

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Summary

Consider an alternate agent or extreme dose reduction of mercaptopurine for patients who are TPMT or NUDT15 poor metabolizers. Start at 30-80% of target dose for patients who are intermediate metabolizers of either TPMT or NUDT15. Start at 20-50% of target dose for patients who are intermediate metabolizers of both TPMT and NUDT15.

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Annotation

This annotation is based on the CPIC® guideline for thiopurines and TPMT and NUDT15.

February 2024 Update

CPIC have updated the recommendations for patients who are intermediate metabolizers of both TPMT and NUDT15. Patients who are intermediate metabolizers or possible intermediate metabolizers for both genes are recommended to begin with a starting dose of 20-50% of the normal dosage. The recommendations in the genotype picker tool and on this annotation page have been updated accordingly.

October 2018 Update

Advance online publication November 2018.

Adapted from Tables 1 and 2 of the 2018 guideline update.

Adapted from Tables 1 and 2 of the 2018 guideline update.

Adapted from Figure 2 and Table 2 of the 2018 guideline update.

May 2016 Update on PharmGKB

Several studies have reported that individuals who carry low-function alleles for NUDT15 are unable to tolerate usual doses of thiopurines. [Articles:25108385, 25624441, 26033531, 26076924, 26405151, 26503813, 26590936, 26735160, 26878724] These alleles are more common among those of Asian ancestry and Hispanic ethnicity than others. [Articles:25624441, 26878724] The dose tolerated by those with two low-function alleles is only ~ 10% that tolerated by those with no low-function NUDT15 or TPMT alleles. [Articles:25624441, 26878724] CPIC is planning a guideline to address NUDT15 variants and possible dosing recommendations for thiopurines.

April 2013 Update

Advance online publication January 2013

March 2011

Advance online publication January 2011.

  • Guidelines regarding the use of pharmacogenomic tests in dosing for azathioprine, thioguanine and mercaptopurine were published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
  • Excerpt from the 2011 thiopurine dosing guidelines:
    • "Thiopurines are most commonly used to treat nonmalignant conditions but are also critical anticancer agents. The approach to dosing adjustments based on TPMT status may differ depending on the clinical indication and the propensity to initiate therapy at higher vs. lower starting doses. We and others advocate testing for TPMT status prior to initiating thiopurine therapy, so that starting dosages can be adjusted accordingly."
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PharmGKB ID

PA166104945