TPMT, NUDT15 and Thioguanine: NUDT15 Poor – Intermediate Metabolizer

Decreased to no NUDT15 enzyme activity. Increased to greatly 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

  • For malignant conditions: Reduce starting dose by 75%. Allow 4–6 weeks to reach steady-state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing thioguanine over other agents.
  • For nonmalignant conditions: Consider alternative nonthiopurine immunosuppressant therapy.

TPMT Intermediate Metabolizer

Decreased TPMT enzyme activity. Increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression based on TPMT alone.

Therapeutic Recommendation

  • For malignant conditions: Reduce starting dose by 75%. Allow 4–6 weeks to reach steady-state after each dose adjustment. In setting of myelosuppression, emphasis should be on reducing thioguanine over other agents.
  • For nonmalignant conditions: Consider alternative nonthiopurine immunosuppressant therapy.

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.

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