Should thiopurine methyltransferase (TPMT) activity be determined before prescribing azathioprine, mercaptopurine, or thioguanine?

The thiopurines azathioprine, mercaptopurine, and thioguanine are prodrugs that are converted to active thioguanine nucleotide metabolites or methylated by thiopurine methyltransferase (TPMT) to compounds with less pharmacologic activity. In the absence of TPMT activity, patients are likely to have higher concentrations of thioguanine nucleotides, which can pose an increased risk of severe life-threatening myelosuppression. Determining TPMT activity, either directly by phenotyping or indirectly by determining the specific genetic allele (different alleles have different enzymatic activity), can help identify patients at greater risk of severe myelosuppression. Therefore, we recommend that TPMT testing be strongly considered before initiating therapy with a thiopurine.