Decreased NUDT15 enzyme activity. Increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression based on NUDT15 alone.
Important Instructions: Please use TPMT phenotype to select the appropriate recommendation below.
TPMT Normal Metabolizer
Normal TPMT enzyme activity. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression based on TPMT alone.
Therapeutic Recommendation
- Reduce starting doses by 50–80%. Allow 2–4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing thioguanine over other agents.
TPMT Intermediate Metabolizer
Decreased TPMT enzyme activity. Increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression based on TPMT alone.
Therapeutic Recommendation
- Reduce starting doses by 50–80%. Allow 2–4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing thioguanine over other agents.
- Due to the additive effect of both genes may require further dose reduction.
TPMT Poor – Intermediate Metabolizer
Decreased to no TPMT enzyme activity. Increased to greatly increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression based on TPMT alone.
Therapeutic Recommendation
- For malignant conditions: Start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily). Allow 4–6 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.
- For nonmalignant conditions: Consider alternative nonthiopurine immunosuppressant therapy.
TPMT Poor Metabolizer
No TPMT enzyme activity. Greatly increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression based on TPMT alone.
Therapeutic Recommendation
- For malignant conditions: Start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily). Allow 4–6 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.
- For nonmalignant conditions: Consider alternative nonthiopurine immunosuppressant therapy.