Mercaptopurine

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

The pharmacogenomic relationship between mercaptopurine and TPMT is well described. See the TPMT VIP and Thiopurines Pathway for more details. Recent work by the Clinical Pharmacogenomics Implementation Consortium (CPIC) has published guidelines for dosing of mercaptopurine in individuals with TPMT variants.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Mercaptopurine.

Excerpt from the Mercaptopurine drug label:
"Mercaptopurine is inactivated via two major pathways. One is thiol methylation, which is catalyzed by the polymorphic enzyme thiopurine S-methyltransferase (TPMT), to form the inactive metabolite methyl-6-MP. TPMT activity is highly variable in patients because of a genetic polymorphism in the TPMT gene. For Caucasians and African Americans, approximately 0.3% (1:300) of patients have two non-functional alleles (homozygous-deficient) of the TPMT gene and have little or no detectable enzyme activity. Approximately 10% of patients have one TPMT non-functional allele (heterozygous) leading to low or intermediate TPMT activity and 90% of individuals have normal TPMT activity with two functional alleles. Homozygous-deficient patients (two non-functional alleles), if given usual doses of mercaptopurine, accumulate excessive cellular concentrations of active thioguanine nucleotides predisposing them to mercaptopurine toxicity (see WARNINGS and PRECAUTIONS). Heterozygous patients with low or intermediate TPMT activity accumulate higher concentrations of active thioguanine nucleotides than people with normal TPMT activity and are more likely to experience mercaptopurine toxicity (see WARNINGS and PRECAUTIONS). TPMT genotyping or phenotyping (red blood cell TPMT activity) can identify patients who are homozygous deficient or have low or intermediate TPMT activity."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Mercaptopurine drug label PDF.