Thioguanine nucleotides (TGN)

Red cell thioguanine nucleotides and methylmercaptopurine levels should be measured 4-6 weeks after the start of thiopurine therapy and 4-6 weeks after any dose adjustment. High levels of methylmercaptopurine are associated with an increased risk of hepatotoxicity. A ratio of methylmercaptopurine:thioguanine of >11 is associated with an increased risk of poor response to therapy.

Report comments:
For children and young adults with ALL, please refer to your protocol directed guidance. The guidelines below apply to azathioprine/6-mercaptopurine immunosuppression.

TGN therapeutic range 235-450 pmol/8x10E8 RBC.

*(TGN <235). TGN below the therapeutic range. Question adherence. Consider dose incrementing if the patient is adherent. If the MeMP/TGN ratio is >11, consider changing therapy to 25% of the target thiopurine dose with 100 mg allopurinol.

*(TGN 235-450). TGN within the therapeutic range. The patient is appropriately dosed. If the patient is not responding to therapy, consider alternative immunosuppressant therapies. Where MeMP > 5700, there is an increased risk of hepatotoxicity, in such patients consider changing therapy to 25% of the target thiopurine dose with 100 mg allopurinol.

*(TGN >450). TGN above the therapeutic range. Dose reduction is advisable if TGN levels are above 550, depending on clinical situation. If patient is not responding to therapy, consider alternative immunosuppressant therapies.

Repeat TGN measurement 4 - 6 weeks after any change in therapy.

References:
Smith et al. Int J Clin Pract. 2013; 67(2):161-9.
Smith et al. J Crohns Colitis. 2012; 6(9):905-12.