Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing by Relling M V, Gardner E E, Sandborn W J, Schmiegelow K, Pui C-H, Yee S W, Stein C M, Carrillo M, Evans W E, Klein T E in Clinical pharmacology and therapeutics (2011).

[PMID: 21270794] PubMed

Abstract

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.

[ hide abstract ]

Discussed In Paper

Loading...

Related In Paper

Rx Annotations

Annotation of CPIC Guideline for azathioprine and TPMT
Annotation of CPIC Guideline for mercaptopurine and TPMT
Annotation of CPIC Guideline for thioguanine and TPMT