Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for thiopurine methyltransferase genotype and thiopurine dosing

Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of individuals who are heterozygotes (~3-14% of the population) show moderate toxicity, and homozygous wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.


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Genomic Competencies

Experts from the disciplines listed below have tagged this resource as fulfulling genomic competencies.

Pharmacist

  • Pharmacogenetics/Pharmacogenomics
    • P1:   To demonstrate an understanding of how genetic variation in a large number of proteins, including drug transporters, drug metabolizing enzymes, direct protein targets of drugs, and other proteins (e.g. signal transduction proteins) influence pharmacokinetics and pharmacodynamics related to pharmacologic effect and drug response
    • P2:   To understand the influence (or lack thereof) of ethnicity in genetic polymorphisms and associations of polymorphisms with drug response
    • P3:   Recognize the availability of evidence based guidelines that synthesize information relevant to genomic/pharmacogenomic tests and selection of drug therapy (e.g. Clinical Pharmacogenomics Implementation Consortium)