Normal NUDT15 enzyme activity. Normal 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
- Start with normal starting dose per disease-specific guidelines. Allow 2 weeks to reach steady-state after each dose adjustment.
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 30–80%. 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 mercaptopurine over other agents.
- If normal starting dose is already < 75 mg/m2/day or < 1.5 mg/kg/day, dose reduction may not be recommended.
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 mercaptopurine 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 mercaptopurine over other agents.
- For nonmalignant conditions: Consider alternative nonthiopurine immunosuppressant therapy.