Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update

Relling, Mary V.; Gardner, E E; Sandborn, W.; Schmiegelow, Kjeld; Ch, Pui; Yee, Sook Wah; Stein, C. Michael; Carrillo, Marta; Evans, William E.; Hicks, J. Kevin; Schwab, Matthias; Klein, Teri E.

doi:10.1038/clpt.2013.4

Cited by 306 publications

(276 citation statements)

References 5 publications

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“…Drug metabolized Clinical response due to alteration in pK Thiopurine methyltransferase [12] Mercaptopurine Thioguanine Azathioprine…”

Section: Genementioning

confidence: 99%

“…Thiopurine methyltransferase genotype and thiopurine dosing [12] Thiopurines are commonly used not only to treat nonmalignant conditions like inflammatory bowel disease, rheumatoid arthritis, and other immune conditions but are also critical anticancer agents in some hematological malignancies. Azathioprine, mercaptopurine, and thioguanine (TG) are all prodrugs that are inactivated by TPMT.…”

Section: • Cyclophosphamide Toxicitymentioning

confidence: 99%

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Pharmacogenetics in oncology: Where we stand today?

Kulkarni

2016

Int J Mol Immuno Oncol.

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Most anticancer medications have narrow therapeutic indices low overall response rates, rapid and severe systemic toxicity and unpredictable efficacy. Therefore, nowhere is pharmacogenomics research needed more than in cancer treatment to guide clinicians to better predict the differences in drug response, efficacy, resistance and toxicity among chemotherapy and targeted therapy patients, and to optimize the treatment regimens based on these differences. [4] In oncology, efficacy and safety of many chemotherapeutic drugs show substantial individual and/or population variability. It can be explained, to a great extent, by gene polymorphism encoding drug-metabolizing enzymes, drug transporters and drug targets which influence the pharmacokinetics and pharmacodynamics and affect clinical outcomes. [5,6] There are several known genes which are largely responsible for variations in drug metabolism and response. The most common are the CYP genes, which encode enzymes that influence the metabolism of more than 80% of current prescription drugs.In addition, the application of pharmacogenomics in oncology is in the discovery of biomarkers that guide selective therapy, ABSTRACTIn a given population, there is considerable variation between individuals with regard to response to as well as toxicity of different drugs. The term "Pharmacogenetics" has largely been used in relation to genes determining drug metabolism, while "Pharmacogenomics" is a broader based term that encompasses all genes in a genome that may determine drug response. In oncology, efficacy and safety of many chemotherapeutic drugs show substantial individual and/or population variability. It can be explained, to a great extent, by gene polymorphism encoding drug-metabolizing enzymes, drug transporters, and drug targets which influence the pharmacokinetics and pharmacodynamics and affect clinical outcomes. Single nucleotide polymorphisms (SNPs) are the most studied genetic variants at present due to ease, accuracy, and reduced the cost of processing as well as due to public availability of online resources for SNPs. Candidate genes for a therapeutic and adverse response can be divided into three categories: Pharmacokinetic, receptor/target, and disease-modifying. Many anticancer drugs are evaluated for their variation in response according to germline variations. This information can be easily incorporated in day-to-day practice to improve efficacy and/or safety of these drugs. In the future, advances gained from pharmacogenetics research will provide information to guide doctors in advising just enough of the right medicine to a person -The practice of "personalized medicine."

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“…Drug metabolized Clinical response due to alteration in pK Thiopurine methyltransferase [12] Mercaptopurine Thioguanine Azathioprine…”

Section: Genementioning

confidence: 99%

Section: • Cyclophosphamide Toxicitymentioning

confidence: 99%

Pharmacogenetics in oncology: Where we stand today?

Kulkarni

2016

Int J Mol Immuno Oncol.

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“…Recommendations include; normal starting dose for homozygous wild type or normal enzyme activity, 30-70% of target dose for heterozygotes or intermediate enzyme activity. Finally, consider alternative therapy or a significant reduction in thiopurine starting dose and reduction in frequency of administration for those with two nonfunctional alleles [20,21]. There is however, a wide variation in clinical practice guidelines across different specialty units [22].…”

Section: Introductionmentioning

confidence: 99%

Thiopurine Methyltransferase Genotype Testing in Paediatric Patients in South Australia. A Retrospective Audit into Prescribing Practices.

Mahindroo¹,

Fletcher²,

Hissaria³

et al. 2017

J Pharmacogenomics Pharmacoproteomics

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“…Although for homozygotes, the dosage should be reduced by 90%. 9 As technology improves, PGx, on the basis of single candidate genes such as the TPMT gene, is evolving into pharmacogenomics, in which genome-wide patterns of single-nucleotide polymorphisms could be identified to help guide therapy. 10 Thus, unlike PGx, pharmacogenomics accounts for interaction effects between multiple genes.…”

mentioning

confidence: 99%

“…5 As an example of PGx testing, when treating acute lymphoblastic leukemia, current standard of practice requires that azathioprine be dosed according to the genotype of the thiopurine methyltransferase (TPMT) enzyme. 9 Specifically, for heterozygotes of mutant TPMT alleles (ie, alleles *2, *3A, *3B, and *4), the dosage of azathioprine should be reduced by 50% to 75%. Although for homozygotes, the dosage should be reduced by 90%.…”

mentioning

confidence: 99%

Public Perceptions of Pharmacogenetics

Zhang¹,

Carleton

Hayden

et al. 2014

Pediatrics

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BACKGROUND AND OBJECTIVES: Pharmacogenetics (PGx) promises to optimize patient response to therapy. However, the public’s acceptance of PGx is not well known, notably when this applies to children. Our objective was to explore perceptions of PGx testing among individuals, who differ from each other by either parental status or educational exposure to PGx, and to explore parents’ views between PGx testing for oneself and PGx testing for their children. METHODS: An exploratory survey was conducted among parents and other adults. Surveys P and C were completed by parents, survey NP by middle-aged nonparents, and survey MS by medical students. RESULTS: Proper explanation before PGx testing appeared to be the most important issue to the respondents (eg, P = 1.55 × 10−38 for survey NP). Respondents who were more knowledgeable about PGx were also more comfortable with PGx testing (eg, P = 2.53 × 10−7 in case of mild disease). When PGx testing was for one’s child, parents valued their own understanding more than their child’s assent (P = 1.57 × 10−17). CONCLUSIONS: The acceptability of PGx testing, either for oneself or for one’s child, seemed to depend on baseline PGx knowledge, but not on parenthood.

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Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update

Cited by 306 publications

References 5 publications

Pharmacogenetics in oncology: Where we stand today?

Pharmacogenetics in oncology: Where we stand today?

Thiopurine Methyltransferase Genotype Testing in Paediatric Patients in South Australia. A Retrospective Audit into Prescribing Practices.

Public Perceptions of Pharmacogenetics

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