Drug/Small Molecule:
azathioprine

Available Guidelines

  1. CPIC Dosing Guideline for azathioprine and TPMT
  2. Dutch Pharmacogenetics Working Group Guideline for azathioprine and TPMT

last updated 01/17/2013

CPIC Dosing Guideline for azathioprine and TPMT

Summary

Consider an alternate agent or extreme dose reduction of azathioprine for patients with low or deficient TPMT activity. Start at 30-70% of target dose for patients with intermediate enzyme activity.

Annotation

April 2013 Update

Advance online publication January 2013.

March 2011

Advance online publication January 2011.

  • Guidelines regarding the use of pharmacogenomic tests in dosing for azathioprine, thioguanine and mercaptopurine were published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
  • Excerpt from the 2011 thiopurine dosing guidelines:
    • "Thiopurines are most commonly used to treat nonmalignant conditions but are also critical anticancer agents. The approach to dosing adjustments based on TPMT status may differ depending on the clinical indication and the propensity to initiate therapy at higher vs. lower starting doses. We and others advocate testing for TPMT status prior to initiating thiopurine therapy, so that starting dosages can be adjusted accordingly."
  • Download and read:

Table 1: Recommended dosing of azathioprine by TPMT phenotype

Adapted from Tables 1 and 2 of the 2011 guideline manuscript.

Phenotype (Genotype) Examples of diplotypes Implications for azathioprine pharmacologic measures Dosing recommendations for azothioprine Classification of recommendations
Homozygous wild-type or normal, high activity (two functional *1 alleles) *1/*1 Lower concentrations of TGN metabolites, higher methylTIMP, this is the "normal" pattern Start with normal starting dose (e.g., 2-3 mg/kg/d) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady state after each dose adjustment. Strong
Heterozygote or intermediate activity (one functional allele - *1, plus one nonfunctional allele - *2, *3A, *3B, *3C, or *4) *1/*2, *1/*3A, *1/*3B, *1/*3C, *1/*4 Moderate to high concentrations of TGN metabolites; low concentrations of methylTIMP If disease treatment normally starts at the "full dose", consider starting at 30-70% of target dose (e.g., 1-1.5 mg/kg/d), and titrate based on tolerance. Allow 2-4 weeks to reach steady state after each dose adjustment. Strong
Homozygous variant, mutant, low, or deficient activity (two nonfunctional alleles - *2, *3A, *3B, *3C, or *4) *3A/*3A, *2/*3A, *3C/*3A, *3C/*4, *3C/*2, *3A/*4 Extremely high concentrations of TGN metabolites; fatal toxicity possible without dose decrease; no methylTIMP metabolites Consider alternative agents. If using azathioprine start with drastically reduced doses (reduce daily dose by 10-fold and dose thrice weekly instead of daily) and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 4-6 weeks to reach steady state after each dose adjustment. Azathioprine is the likely cause of myelosuppression. Strong

last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for azathioprine and TPMT

Summary

Select an alternative drug or reduce the initial dose of azathioprine for patients carrying one or two inactive TPMT alleles.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for azathioprine based on TPMT genotype [Article:21412232]. They recommend selecting an alternative drug or reducing the initial dose for patients carrying inactive alleles.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
IM (one inactive allele: *2, *3, *4-*18) Select alternative drug or reduce dose by 50%. Increase dose in response of hematologic monitoring and efficacy. Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): Failure of lifesaving therapy e.g. anticipated myelosuppression; prevention of breast cancer relapse; arrhythmia; neutropenia < 0.5x109/l; leucopenia < 1.0x109/l; thrombocytopenia < 25x109/l; life-threatening complications from diarrhea.
PM (two inactive alleles: *2, *3, *4-*18) Select alternative drug or reduce dose by 90%. Increase dose in response of hematologic monitoring and efficacy. Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for azathioprine and TPMT

This label is on the FDA Biomarker List
Genetic testing recommended

Summary

The azathioprine (Imuran) FDA-approved drug label recommends testing for TPMT genotype or phenotype to identify patients who are at increased risk of myelotoxicity: those with low or absent TPMT activity. The label also recommends a further reduced dosage or alternative therapies in patients with low or absent TPMT activity treated with azathioprine and allopurinol concomitantly.

Annotation

Excerpts from the azathioprine (Imuran) drug label:

Patients with intermediate thiopurine S-methyl transferase (TPMT) activity may be at an increased risk of myelotoxicity if receiving conventional doses of IMURAN. Patients with low or absent TPMT activity are at an increased risk of developing severe, life-threatening myelotoxicity if receiving conventional doses of IMURAN. TPMT genotyping or phenotyping can help identify patients who are at an increased risk for developing IMURAN toxicity


TPMT Testing: It is recommended that consideration be given to either genotype or phenotype patients for TPMT. Phenotyping and genotyping methods are commercially available. The most common non-functional alleles associated with reduced levels of TPMT activity are TPMT*2, TPMT*3A and TPMT*3C. Patients with two nonfunctional alleles (homozygous) have low or absent TPMT activity and those with one non-functional allele (heterozygous) have intermediate activity. Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have received recent blood transfusions. TPMT testing may also be considered in patients with abnormal CBC results that do not respond to dose reduction. Early drug discontinuation in these patients is advisable. TPMT TESTING CANNOT SUBSTITUTE FOR COMPLETE BLOOD COUNT (CBC) MONITORING IN PATIENTS RECEIVING IMURAN. See CLINICAL PHARMACOLOGY, WARNINGS, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION sections.


One of the pathways for inactivation of azathioprine is inhibited by allopurinol. Patients receiving IMURAN and allopurinol concomitantly should have a dose reduction of IMURAN, to approximately 1/3 to 1/4 the usual dose. It is recommended that a further dose reduction or alternative therapies be considered for patients with low or absent TPMT activity receiving IMURAN and allopurinol because both TPMT and XO inactivation pathways are affected.

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

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Genes and/or phenotypes found in this label

  • Colitis, Ulcerative
    • Warnings section
    • source: PHONT
  • Crohn Disease
    • Warnings section
    • source: PHONT
  • Drug Toxicity
    • Dosage & administration section, Warnings section, Adverse reactions section, Clinical pharmacology section, Precautions section, toxicity
    • source: FDA Label
  • Inflammatory Bowel Diseases
    • Warnings section
    • source: PHONT
  • Neoplasms
    • Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • TPMT
    • Dosage & administration section, Warnings section, Adverse reactions section, Clinical pharmacology section, Precautions section, toxicity, metabolism/PK
    • source: FDA Label
  • XDH
    • Clinical pharmacology section, Precautions section, metabolism/PK
    • source: FDA Label

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
DMET Plus (Affymetrix, Inc) Variant in TPMT
Prometheus TPMT Genetics TPMT Not available
TPMT GenotypR rs1142345 , rs1800460 , rs1800462

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA HLA-DQA1 *02:01 N/A N/A N/A
No VIP available CA VA HLA-DRB1 *07:01:01:01 N/A N/A N/A
No VIP available CA VA TPMT *1 N/A N/A N/A
No VIP available CA VA TPMT *1S N/A N/A N/A
No VIP available CA VA TPMT *2 N/A N/A N/A
No VIP available CA VA TPMT *3A N/A N/A N/A
No VIP available CA VA TPMT *3B N/A N/A N/A
No VIP available CA VA TPMT *3C N/A N/A N/A
No VIP available No VIP available VA TPMT *3D N/A N/A N/A
No VIP available No VIP available VA TPMT *3E N/A N/A N/A
No VIP available CA No VIP available TPMT *4 N/A N/A N/A
No VIP available CA VA TPMT *6 N/A N/A N/A
No VIP available CA No VIP available TPMT *7 N/A N/A N/A
No VIP available CA No VIP available TPMT *8 N/A N/A N/A
No VIP available CA No VIP available TPMT *9 N/A N/A N/A
No VIP available CA No VIP available TPMT *11 N/A N/A N/A
No VIP available CA No VIP available TPMT *12 N/A N/A N/A
No VIP available CA No VIP available TPMT *14 N/A N/A N/A
No VIP available CA No VIP available TPMT *16 N/A N/A N/A
No VIP available CA No VIP available TPMT *17 N/A N/A N/A
No VIP available CA No VIP available TPMT *18 N/A N/A N/A
No VIP available CA No VIP available TPMT *20 N/A N/A N/A
No VIP available CA No VIP available TPMT *21 N/A N/A N/A
No VIP available CA No VIP available TPMT *22 N/A N/A N/A
No VIP available CA No VIP available TPMT *23 N/A N/A N/A
No VIP available CA VA
rs1127354 194C>A, 194C>G, 194C>T, 286C>A, 286C>G, 286C>T, 3133842C>A, 3133842C>G, 3133842C>T, 3193842C>A, 3193842C>G, 3193842C>T, 43C>A, 43C>G, 43C>T, 49-62C>A, 49-62C>G, 49-62C>T, 67-789C>A, 67-789C>G, 67-789C>T, 8787C>A, 8787C>G, 8787C>T, 94C>A, 94C>G, 94C>T, ITPA, ITPA: 94C>A, P32T, Pro15Ala, Pro15Ser, Pro15Thr, Pro32Ala, Pro32Ser, Pro32Thr
C > G
C > T
C > A
Not Available
Pro15Thr
rs1142345 18070918T>C, 18130918T>C, 29457A>G, 719A>G, TPMT*3C, Tyr240Cys
T > C
Missense
Tyr240Cys
No VIP available CA VA
rs116855232 29599855C>T, 415C>T, 48619855C>T, Arg139Cys
C > T
Missense
Arg139Cys
rs1800460 18079228C>T, 18139228C>T, 21147G>A, 460G>A, Ala154Thr, TPMT*3B
C > T
Missense
Ala154Thr
rs1800462 16420G>C, 18083955C>G, 18143955C>G, 238G>C, Ala80Pro, TPMT*2, TPMT:238G>C
C > G
Missense
Ala80Pro
VIP No Clinical Annotations available No Variant Annotations available
rs1800584 18071012C>T, 18131012C>T, 29363G>A, 626-1G>A, TPMT*4
C > T
Acceptor
No VIP available No Clinical Annotations available VA
rs1801131 1040A>C, 11208431T>G, 11794419T>G, 1286A>C, 1409A>C, 16685A>C, A1298C, Glu347Ala, Glu429Ala, Glu470Ala, MTHFR:1298A>C
T > G
Not Available
Glu347Ala
No VIP available No Clinical Annotations available VA
rs1801133 11210333G>A, 11796321G>A, 14783C>T, 419C>T, 665C>T, 677C>T, 788C>T, A222V, Ala140Val, Ala222Val, Ala263Val, C677T, MTHFR: c.677C>T, MTHFR:667C>T, p.A222V
G > A
Not Available
Ala140Val
No VIP available CA VA
rs2647087 32621049A>C, 32681049A>C, 3913118A>C, 3962959C>C, 4017591A>C, 4112694A>C, 4126664A>C, 4138195C>C
A > C
Not Available
No VIP available No Clinical Annotations available VA
rs3765534 2269G>A, 8905091C>T, 95815415C>T, ABCC4:E857K, ABCC4:G2269A, Glu757Lys
C > T
Missense
Glu757Lys
No VIP available CA VA
rs55754655 201526330A>G, 3404A>G, 51735748A>G, AOX1: c.3404A>G, Asn1135Ser
A > G
Missense
Asn1135Ser
No VIP available No Clinical Annotations available VA
rs7270101 124+21A>C, 224+21A>C, 3133893A>C, 316+21A>C, 3193893A>C, 49-11A>C, 67-738A>C, 73+21A>C, 8838A>C
A > C
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Azathioprin
  • Azathioprine Sodium
  • Azatioprin
  • Azothioprine
Trade Names
  • Azamun
  • Azanin
  • Azasan
  • Ccucol
  • Imuran
  • Imurek
  • Imurel
  • Muran
Brand Mixture Names

PharmGKB Accession Id:
PA448515

Description

An immunosuppressive pro-drug. It is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis.

Source: Drug Bank

Indication

For use in rheumatoid arthritis, preventing renal transplant rejection, Crohn's disease, and colitis.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Azathioprine antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. Its mechanism of action is likely due to incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity.

Source: Drug Bank

Pharmacology

Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. It is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication.

Source: Drug Bank

Food Interaction

Take with food to reduce irritation.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Primarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid via a non-enzymatica process. 6-mercaptopurine is subsequently metabolized primarily by xanthine oxidase.

Source: Drug Bank

Protein Binding

Azathioprine and the metabolite mercaptopurine are moderately bound to serum proteins (30%).

Source: Drug Bank

Absorption

Well absorbed following oral administration.

Source: Drug Bank

Half-Life

Approximately 5 hours for the unchanged drug and its metabolites.

Source: Drug Bank

Toxicity

The oral LD 50 for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death.

Source: Drug Bank

Chemical Properties

Chemical Formula

C9H7N7O2S

Source: Drug Bank

Isomeric SMILES

CN1C=NC(=C1SC2=NC=NC3=C2NC=N3)[N+](=O)[O-]

Source: Drug Bank

Canonical SMILES

CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-]

Source: Drug Bank

Average Molecular Weight

277.263

Source: PharmGKB

Monoisotopic Molecular Weight

277.038193193

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ADSL (source: Drug Bank)
AMPD1 (source: Drug Bank)
AMPD2 (source: Drug Bank)
AMPD3 (source: Drug Bank)
GMPR (source: Drug Bank)
GMPR2 (source: Drug Bank)
GMPS (source: Drug Bank)
HPRT1 (source: Drug Bank)
IMPDH1 (source: Drug Bank)
IMPDH2 (source: Drug Bank)
PPAT (source: Drug Bank)

Drug Interactions

Drug Description
azathioprine Allopurinol increases the effect of thiopurine (source: Drug Bank)
azathioprine Allopurinol increases the effect of thiopurine (source: Drug Bank)
azathioprine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
azathioprine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
acenocoumarol The thiopurine decreases the anticoagulant effect (source: Drug Bank)
acenocoumarol Azathioprine may decrease the anticoagulant effect of acenocoumarol. (source: Drug Bank)
allopurinol Allopurinol increases the effect of thiopurine (source: Drug Bank)
allopurinol Allopurinol increases the effect of thiopurine (source: Drug Bank)
anisindione Azathioprine may decrease the anticoagulant effect of anisindione. (source: Drug Bank)
atracurium The agent decreases the effect of the muscle relaxant (source: Drug Bank)
dicumarol The thiopurine decreases the anticoagulant effect (source: Drug Bank)
dicumarol Azathioprine may decrease the anticoagulant effect of dicumarol. (source: Drug Bank)
doxacurium The agent decreases the effect of the muscle relaxant (source: Drug Bank)
gallamine triethiodide The agent decreases the effect of the muscle relaxant (source: Drug Bank)
mesalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
mesalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
metocurine The agent decreases the effect of the muscle relaxant (source: Drug Bank)
mivacurium The agent decreases the effect of the muscle relaxant (source: Drug Bank)
mivacurium The agent decreases the effect of the muscle relaxant (source: Drug Bank)
olsalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
olsalazine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
pancuronium The agent decreases the effect of the muscle relaxant (source: Drug Bank)
pancuronium The agent decreases the effect of the muscle relaxant (source: Drug Bank)
sulfasalazine The 5-ASA derivative increase the toxicity of thiopurine (source: Drug Bank)
sulfasalazine The 5-ASA derivative increase the toxicity of thiopurine (source: Drug Bank)
tubocurarine The agent decreases the effect of the muscle relaxant (source: Drug Bank)
tubocurarine The agent decreases the effect of the muscle relaxant (source: Drug Bank)
vecuronium The agent decreases the effect of the muscle relaxant (source: Drug Bank)
warfarin The thiopurine decreases the anticoagulant effect (source: Drug Bank)
warfarin Azathioprine may decrease the anticoagulant effect of warfarin. (source: Drug Bank)
azathioprine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
azathioprine The 5-ASA derivative increases the toxicity of thiopurine (source: Drug Bank)
azathioprine Trandolapril may increase the risk of neutropenia. Monitor for increased toxic effects of Azathioprine if Trandolapril is initiated or dose increased. (source: Drug Bank)
azathioprine Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
May Prevent
Contraindicated With

Publications related to azathioprine: 182

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nature genetics. 2014. Heap Graham A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Thiopurine monitoring in children with inflammatory bowel disease: a systematic review. British journal of clinical pharmacology. 2014. Konidari Anastasia, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nature genetics. 2014. Yang Suk-Kyun, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Implementation of TPMT testing. British journal of clinical pharmacology. 2014. Lennard Lynne. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clinical pharmacology and therapeutics. 2013. Van Driest Sara L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
TPMT genetic variants are associated with increased rejection with azathioprine use in heart transplantation. Pharmacogenetics and genomics. 2013. Liang Jackson J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thiopurine methyltransferase genotype-phenotype discordance and thiopurine active metabolite formation in childhood acute lymphoblastic leukaemia. British journal of clinical pharmacology. 2013. Lennard Lynne, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of disease-modifying antirheumatic drugs in rheumatoid arthritis: towards personalized medicine. Pharmacogenomics. 2013. Umićević Mirkov Maša, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Nomenclature for alleles of the thiopurine methyltransferase gene. Pharmacogenetics and genomics. 2013. Appell Malin L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update. Clinical pharmacology and therapeutics. 2013. Relling M V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A new thiopurine s-methyltransferase haplotype associated with intolerance to azathioprine. Journal of clinical pharmacology. 2013. Colleoni Lara, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Optimising outcome on thiopurines in inflammatory bowel disease by co-prescription of allopurinol. Journal of Crohn's & colitis. 2012. Smith Melissa A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record. Clinical pharmacology and therapeutics. 2012. Hicks J K, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity. Human molecular genetics. 2012. Stocco Gabriele, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genetic variants of thiopurine and folate metabolic pathways determine 6-MP-mediated hematological toxicity in childhood ALL. Pharmacogenomics. 2012. Dorababu Patchva, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacogenetic analysis of pediatric patients with acute lymphoblastic leukemia: a possible association between survival rate and ITPA polymorphism. PloS one. 2012. Kim Hyery, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thiopurine S-methyltransferase (TPMT) polymorphisms in children with acute lymphoblastic leukemia, and the need for reduction or cessation of 6-mercaptopurine doses during maintenance therapy: the Polish multicenter analysis. Pediatric blood & cancer. 2011. Peregud-Pogorzelski Jarosław, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients. Alimentary pharmacology & therapeutics. 2011. González-Lama Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side effects and clinical response in patients with inflammatory bowel disease receiving Azathioprine. Journal of gastrointestinal and liver diseases : JGLD. 2011. Zabala-Fernández William, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thiopurine S-methyltransferase polymorphism in Iranian kidney transplant recipients. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2011. Aghdaie Mahdokht Hossein, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Azathioprine-related myelosuppression in a patient homozygous for TPMT*3A. Nature reviews. Nephrology. 2011. Budhiraja Pooja, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. Pharmacogenomics. 2011. Patterson Scott D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Nodular regenerative liver hyperplasia as a complication of azathioprine-containing immunosuppressive treatment for Crohn's disease. Immunopharmacology and immunotoxicology. 2011. Błogowski Wojciech, et al. PubMed
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Novel thiopurine methyltransferase variant TPMT*28 results in a misdiagnosis of TPMT deficiency. Inflammatory bowel diseases. 2011. Landy J, et al. PubMed
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A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study. Pharmacogenomics. 2011. Newman William G, et al. PubMed
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Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy. British journal of clinical pharmacology. 2011. Adam de Beaumais Tiphaine, et al. PubMed
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Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clinical pharmacology and therapeutics. 2011. Relling M V, et al. PubMed
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Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
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Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
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Thiopurine methyltransferase predicts the extent of cytotoxicty and DNA damage in astroglial cells after thioguanine exposure. PloS one. 2011. Hosni-Ahmed Amira, et al. PubMed
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Identifying genomic and developmental causes of adverse drug reactions in children. Pharmacogenomics. 2010. Becker Mara L, et al. PubMed
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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease. Journal of gastroenterology. 2010. Ban Hiromistu, et al. PubMed
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Thiopurine pathway. Pharmacogenetics and genomics. 2010. Zaza Gianluigi, et al. PubMed
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Thiopurine S-methyltransferase gene polymorphism and 6-mercaptopurine dose intensity in Indian children with acute lymphoblastic leukemia. Leukemia research. 2010. Kapoor Gauri, et al. PubMed
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Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy. British journal of pharmacology. 2010. de Graaf P, et al. PubMed
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Thiopurine S-methyltransferase polymorphisms and thiopurine toxicity in treatment of inflammatory bowel disease. World journal of gastroenterology : WJG. 2010. Dong Xian-Wen, et al. PubMed
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Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial. Gut. 2010. Reinisch Walter, et al. PubMed
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Very important pharmacogene summary: thiopurine S-methyltransferase. Pharmacogenetics and genomics. 2010. Wang Liewei, et al. PubMed
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Drug transporter pharmacogenetics in nucleoside-based therapies. Pharmacogenomics. 2010. Errasti-Murugarren Ekaitz, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: functional characterization of a novel rapidly degraded variant allozyme. Biochemical pharmacology. 2010. Feng Qiping, et al. PubMed
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Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2010. Ansari A, et al. PubMed
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Human lymphoblastoid cell line panels: novel tools for assessing shared drug pathways. Pharmacogenomics. 2010. Morag Ayelet, et al. PubMed
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Pharmacogenomics in the treatment of inflammatory bowel disease. Pharmacogenomics. 2010. Smith Melissa A, et al. PubMed
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Thiopurine S-methyltransferase genotype and the use of thiopurines in paediatric inflammatory bowel disease Greek patients. Journal of clinical pharmacy and therapeutics. 2010. Gazouli M, et al. PubMed
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Are patients with intermediate TPMT activity at increased risk of myelosuppression when taking thiopurine medications?. Pharmacogenomics. 2010. Higgs Jenny E, et al. PubMed
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Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study. Journal of clinical gastroenterology. 2010. Kim Jae Hak, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics in a large-scale healthy Italian-Caucasian population: differences in enzyme activity. Pharmacogenomics. 2009. Serpe Loredana, et al. PubMed
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Warfarin interactions with substances listed in drug information compendia and in the FDA-approved label for warfarin sodium. Clinical pharmacology and therapeutics. 2009. Anthony M, et al. PubMed
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Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2009. Smith M A, et al. PubMed
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Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukemia on Berlin-Frankfurt-Münster protocols. Blood. 2009. Stanulla Martin, et al. PubMed
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Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain. European journal of human genetics : EJHG. 2009. Gurwitz David, et al. PubMed
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Impact of the heterozygous TPMT*1/*3C genotype on azathioprine-induced myelosuppression in kidney transplant recipients in Thailand. Clinical therapeutics. 2009. Vannaprasaht Suda, et al. PubMed
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Adverse reactions to azathioprine cannot be predicted by thiopurine S-methyltransferase genotype in Japanese patients with inflammatory bowel disease. Journal of gastroenterology and hepatology. 2009. Takatsu Noritaka, et al. PubMed
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Pro32Thr polymorphism of inosine triphosphate pyrophosphatase gene predicts efficacy of low-dose azathioprine for patients with systemic lupus erythematosus. Clinical pharmacology and therapeutics. 2009. Okada Y, et al. PubMed
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ADME pharmacogenetics: current practices and future outlook. Expert opinion on drug metabolism & toxicology. 2009. Grossman Iris. PubMed
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Heterozygosity at the TPMT gene locus, augmented by mutated MTHFR gene, predisposes to 6-MP related toxicities in childhood ALL patients. Leukemia. 2009. Karas-Kuzelicki N, et al. PubMed
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Application of SNaPshot for analysis of thiopurine methyltransferase gene polymorphism. The Indian journal of medical research. 2009. Kapoor Gauri, et al. PubMed
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Relationships between thiopurine S-methyltransferase polymorphism and azathioprine-related adverse drug reactions in Chinese renal transplant recipients. European journal of clinical pharmacology. 2009. Xin Hua-Wen, et al. PubMed
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Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2009. Schmiegelow K, et al. PubMed
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TPMT genetic variations in populations of the Russian Federation. Pediatric blood & cancer. 2009. Samochatova Elena V, et al. PubMed
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Use of pharmacogenetics, enzymatic phenotyping, and metabolite monitoring to guide treatment with azathioprine in patients with systemic lupus erythematosus. The Journal of rheumatology. 2009. Askanase Anca D, et al. PubMed
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Thiopurine methyltransferase gene polymorphisms in Chinese patients with inflammatory bowel disease. Digestion. 2009. Cao Qian, et al. PubMed
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Initial clinical experience with allopurinol-thiopurine combination therapy in pediatric inflammatory bowel disease. Inflammatory bowel diseases. 2008. Rahhal Riad M, et al. PubMed
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Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity. Neuro endocrinology letters. 2009. Kolorz Michal, et al. PubMed
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Thiopurine S-methyltransferase (TPMT) gene polymorphism in Brazilian children with acute lymphoblastic leukemia: association with clinical and laboratory data. Therapeutic drug monitoring. 2008. Silva Marcilene Rezende, et al. PubMed
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Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2008. Ansari A, et al. PubMed
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Functional characterization of 23 allelic variants of thiopurine S-methyltransferase gene (TPMT*2 - *24). Pharmacogenetics and genomics. 2008. Ujiie Shuta, et al. PubMed
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Long-term outcome of using allopurinol co-therapy as a strategy for overcoming thiopurine hepatotoxicity in treating inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2008. Ansari A, et al. PubMed
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Characterisation of novel defective thiopurine S-methyltransferase allelic variants. Biochemical pharmacology. 2008. Garat A, et al. PubMed
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Thiopurine dose in intermediate and normal metabolizers of thiopurine methyltransferase may differ three-fold. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2008. Gardiner Sharon J, et al. PubMed
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Trinucleotide repeat variants in the promoter of the thiopurine S-methyltransferase gene of patients exhibiting ultra-high enzyme activity. Pharmacogenetics and genomics. 2008. Roberts Rebecca L, et al. PubMed
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Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency. American journal of hematology. 2008. Yenson Paul R, et al. PubMed
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Thiopurine-methyltransferase and inosine triphosphate pyrophosphatase polymorphism in a liver transplant recipient developing nodular regenerative hyperplasia on low-dose azathioprine. European journal of gastroenterology & hepatology. 2008. Buster Erik H C J, et al. PubMed
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Thiopurine S-methyltransferase (TPMT) pharmacogenetics: three new mutations and haplotype analysis in the Estonian population. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2008. Tamm Riin, et al. PubMed
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Analysis of thiopurine S-methyltransferase genotypes in Japanese patients with inflammatory bowel disease. Internal medicine (Tokyo, Japan). 2008. Ban Hiromitsu, et al. PubMed
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Thiopurine S-methyltransferase gene (TMPT) polymorphisms in a Mexican population of healthy individuals and leukemic patients. Medical oncology (Northwood, London, England). 2008. Taja-Chayeb Lucia, et al. PubMed
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The low frequency of defective TPMT alleles in Turkish population: a study on pediatric patients with acute lymphoblastic leukemia. American journal of hematology. 2007. Tumer Tugba Boyunegmez, et al. PubMed
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Explaining TPMT genotype/phenotype discrepancy by haplotyping of TPMT*3A and identification of a novel sequence variant, TPMT*23. Pharmacogenetics and genomics. 2007. Lindqvist Malin, et al. PubMed
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IMPDH1 promoter mutations in a patient exhibiting azathioprine resistance. The pharmacogenomics journal. 2007. Roberts R L, et al. PubMed
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Pharmacogenetic significance of inosine triphosphatase. Pharmacogenomics. 2007. Bierau Jörgen, et al. PubMed
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Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2007. Winter J W, et al. PubMed
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MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease. Inflammatory bowel diseases. 2007. Mendoza Juan L, et al. PubMed
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Current use of pharmacogenetic testing: a national survey of thiopurine methyltransferase testing prior to azathioprine prescription. Journal of clinical pharmacy and therapeutics. 2007. Fargher E A, et al. PubMed
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Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China). Clinica chimica acta; international journal of clinical chemistry. 2007. Zhang Li-Rong, et al. PubMed
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Thiopurine S-methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases. Liver international : official journal of the International Association for the Study of the Liver. 2007. Tamori Akihiro, et al. PubMed
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Monitoring of thiopurine methyltransferase activity in postsurgical patients with Crohn's disease during 1 year of treatment with azathioprine or mesalazine. Therapeutic drug monitoring. 2007. Dilger Karin, et al. PubMed
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TPMT genotype and its clinical implication in renal transplant recipients with azathioprine treatment. Journal of clinical pharmacy and therapeutics. 2006. Song D-K, et al. PubMed
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Overview of the pharmacoeconomics of pharmacogenetics. Pharmacogenomics. 2006. Dervieux Thierry, et al. PubMed
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Analysis of thiopurine S-methyltransferase polymorphism in the population of Serbia and Montenegro and mercaptopurine therapy tolerance in childhood acute lymphoblastic leukemia. Therapeutic drug monitoring. 2006. Dokmanovic Lidija, et al. PubMed
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The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clinical pharmacology and therapeutics. 2006. Lennard Lynne, et al. PubMed
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Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut. 2006. Hindorf U, et al. PubMed
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Three novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) - association with decreased enzyme function. Human mutation. 2006. Schaeffeler Elke, et al. PubMed
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Divergent activities of human glutathione transferases in the bioactivation of azathioprine. Molecular pharmacology. 2006. Eklund Birgitta I, et al. PubMed
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The frequency and significance of thiopurine S-methyltransferase gene polymorphisms in azathioprine-treated renal transplant recipients. The British journal of dermatology. 2006. Moloney F J, et al. PubMed
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Pharmacogenetics of thiopurine therapy in paediatric IBD patients. Alimentary pharmacology & therapeutics. 2006. De Ridder L, et al. PubMed
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Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006. Meggitt Simon J, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: insights, challenges and future directions. Oncogene. 2006. Wang L, et al. PubMed
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Predictors of immunomodulator use as early therapy in pediatric Crohn's disease. Journal of clinical gastroenterology. 2006. Jacobstein Douglas A, et al. PubMed
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Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2006. Zelinkova Zuzana, et al. PubMed
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Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins. Journal of immunology (Baltimore, Md. : 1950). 2006. Poppe Daniela, et al. PubMed
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Pharmacogenomics and individualized drug therapy. Annual review of medicine. 2006. Eichelbaum Michel, et al. PubMed
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TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2005. Stocco G, et al. PubMed
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Thiopurine S-methyltransferase phenotype-genotype correlation in hemodialyzed patients. Pharmacological reports : PR. 2006. Chrzanowska Maria, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: genotype to phenotype correlation in the Slovenian population. Pharmacology. 2006. Milek M, et al. PubMed
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Thiopurine methyltransferase genotype and phenotype status in Japanese patients with systemic lupus erythematosus. Biological & pharmaceutical bulletin. 2005. Okada Yuko, et al. PubMed
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Thiopurine S-methyltransferase pharmacogenetics: variant allele functional and comparative genomics. Pharmacogenetics and genomics. 2005. Salavaggione Oreste E, et al. PubMed
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Thiopurine methyltransferase and 6-thioguanine nucleotide measurement: early experience of use in clinical practice. Internal medicine journal. 2005. Gearry R B, et al. PubMed
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A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. The American journal of gastroenterology. 2005. Dubinsky Marla C, et al. PubMed
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The impact of thiopurine s-methyltransferase polymorphism on azathioprine-induced myelotoxicity in renal transplant recipients. Therapeutic drug monitoring. 2005. Kurzawski Mateusz, et al. PubMed
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Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2005. Breen David P, et al. PubMed
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Azathioprine induced nodular regenerative hyperplasia in IBD patients. Gastroentérologie clinique et biologique. 2005. Daniel Fady, et al. PubMed
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Thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events. Journal of the neurological sciences. 2005. Heckmann Jeannine M, et al. PubMed
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Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA : the journal of the American Medical Association. 2005. Stanulla Martin, et al. PubMed
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Identification and functional analysis of two rare allelic variants of the thiopurine S-methyltransferase gene, TPMT*16 and TPMT*19. Biochemical pharmacology. 2005. Hamdan-Khalil Rima, et al. PubMed
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Thiopurine S-methyltransferase polymorphisms and the relationship between the mutant alleles and the adverse effects in systemic lupus erythematosus patients taking azathioprine. Clinical and experimental rheumatology. 2005. Jun J B, et al. PubMed
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Guidelines for prescribing azathioprine in dermatology. The British journal of dermatology. 2004. Anstey A V, et al. PubMed
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Assessment of thiopurine methyltransferase and metabolite formation during thiopurine therapy: results from a large Swedish patient population. Therapeutic drug monitoring. 2004. Hindorf Ulf, et al. PubMed
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Thiopurine S-methyltransferase genotype predicts azathioprine-induced myelotoxicity in kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2004. Formea Christine M, et al. PubMed
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Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine. Pharmacogenetics. 2004. Gearry Richard B, et al. PubMed
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Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease. Scandinavian journal of gastroenterology. 2004. Hindorf U, et al. PubMed
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Allele frequency of inosine triphosphate pyrophosphatase gene polymorphisms in a Japanese population. Nucleosides, nucleotides & nucleic acids. 2004. Marinaki A M, et al. PubMed
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The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation. Transplant international : official journal of the European Society for Organ Transplantation. 2004. Fabre Margarete A, et al. PubMed
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Comprehensive analysis of thiopurine S-methyltransferase phenotype-genotype correlation in a large population of German-Caucasians and identification of novel TPMT variants. Pharmacogenetics. 2004. Schaeffeler Elke, et al. PubMed
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Phenotype and genotype for thiopurine methyltransferase activity in the French Caucasian population: impact of age. European journal of clinical pharmacology. 2004. Ganiere-Monteil Catherine, et al. PubMed
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Identification of two novel sequence variants affecting thiopurine methyltransferase enzyme activity. Pharmacogenetics. 2004. Lindqvist Malin, et al. PubMed
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Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy. Therapeutic drug monitoring. 2004. Evans William E. PubMed
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Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics. 2004. Marinaki Anthony M, et al. PubMed
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Pyrosequencing of TPMT alleles in a general Swedish population and in patients with inflammatory bowel disease. Clinical chemistry. 2004. Haglund Sofie, et al. PubMed
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Distribution of ITPA P32T alleles in multiple world populations. Journal of human genetics. 2004. Marsh Sharon, et al. PubMed
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Mistaken identity: misclassification of TPMT phenotype following blood transfusion. European journal of gastroenterology & hepatology. 2003. Cheung Seau-Tak, et al. PubMed
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In vitro characterization of four novel non-functional variants of the thiopurine S-methyltransferase. Biochemical and biophysical research communications. 2003. Hamdan-Khalil Rima, et al. PubMed
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Drug methylation in cancer therapy: lessons from the TPMT polymorphism. Oncogene. 2003. Krynetski Eugene, et al. PubMed
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Phenotypic and genotypic analysis of thiopurine s-methyltransferase polymorphism in the bulgarian population. Therapeutic drug monitoring. 2003. Indjova Dessislava, et al. PubMed
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Genetic polymorphism of thiopurine S-methyltransferase in Argentina. Annals of clinical biochemistry. 2003. Laróvere L E, et al. PubMed
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A novel TPMT missense mutation associated with TPMT deficiency in a 5-year-old boy with ALL. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003. Schaeffeler E, et al. PubMed
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Thiopurine methyltransferase phenotypes and genotypes in Brazilians. Pharmacogenetics. 2003. Reis Marcelo, et al. PubMed
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CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. The Journal of clinical investigation. 2003. Tiede Imke, et al. PubMed
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Thiopurine methyltransferase genotype distribution in patients with Crohn's disease. Alimentary pharmacology & therapeutics. 2003. Reuther L O, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine. Gut. 2003. Kaskas B A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients?. Rheumatology (Oxford, England). 2003. Corominas H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Practical pharmacogenetics: the cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine. The Journal of rheumatology. 2002. Marra Carlo A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2002. Ansari A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Determination of thiopurine methyltransferase genotype or phenotype optimizes initial dosing of azathioprine for the treatment of Crohn's disease. Journal of clinical gastroenterology. 2002. Regueiro Miguel, et al. PubMed
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Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism. Pharmacogenetics. 2002. Schwab Matthias, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction between azathioprine and aminosalicylates: an in vivo study in patients with Crohn's disease. Alimentary pharmacology & therapeutics. 2002. Dewit O, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The thiopurine S-methyltransferase gene locus -- implications for clinical pharmacogenomics. Pharmacogenomics. 2002. McLeod Howard L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thiopurine methyltransferase polymorphisms in a multiracial asian population and children with acute lymphoblastic leukemia. Journal of pediatric hematology/oncology. 2002. Kham S K Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Influence of the variable number of tandem repeats located in the promoter region of the thiopurine methyltransferase gene on enzymatic activity. Clinical pharmacology and therapeutics. 2001. Alves S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Rational dosing of azathioprine and 6-mercaptopurine. Gut. 2001. Sandborn W J. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genotype-phenotype correlation for thiopurine S-methyltransferase in healthy Italian subjects. European journal of clinical pharmacology. 2001. Rossi A M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2001. Evans W E, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms of thiopurine S-methyltransferase and 6-mercaptopurine toxicity in Japanese children with acute lymphoblastic leukaemia. Pharmacogenetics. 2001. Ando M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis. European journal of gastroenterology & hepatology. 2001. Russmann S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000. Colombel J F, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000. Dubinsky M C, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients. Transplantation. 2000. Sebbag L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Severe 6-thioguanine-induced marrow aplasia in a child with acute lymphoblastic leukemia and inherited thiopurine methyltransferase deficiency. Journal of pediatric hematology/oncology. 2000. McBride K L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. Journal of the National Cancer Institute. 1999. Relling M V, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Enhanced proteasomal degradation of mutant human thiopurine S-methyltransferase (TPMT) in mammalian cells: mechanism for TPMT protein deficiency inherited by TPMT*2, TPMT*3A, TPMT*3B or TPMT*3C. Pharmacogenetics. 1999. Tai H L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Analysis of thiopurine methyltransferase variant alleles in childhood acute lymphoblastic leukaemia. British journal of haematology. 1999. McLeod H L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thiopurine methyltransferase pharmacogenetics: alternative molecular diagnosis and preliminary data from Northern Portugal. Pharmacogenetics. 1999. Alves S, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Human molecular genetics. 1999. Hon Y Y, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics. 1999. Collie-Duguid E S, et al. PubMed
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Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Annals of internal medicine. 1998. Black A J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions. Therapeutic drug monitoring. 1998. Lennard L. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Isolation of a human thiopurine S-methyltransferase (TPMT) complementary DNA with a single nucleotide transition A719G (TPMT*3C) and its association with loss of TPMT protein and catalytic activity in humans. Clinical pharmacology and therapeutics. 1998. Loennechen T, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Human thiopurine methyltransferase pharmacogenetics. Kindred with a terminal exon splice junction mutation that results in loss of activity. The Journal of clinical investigation. 1998. Otterness D M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency. Acta paediatrica (Oslo, Norway : 1992). 1998. Andersen J B, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Detection of known and new mutations in the thiopurine S-methyltransferase gene by single-strand conformation polymorphism analysis. Human mutation. 1998. Spire-Vayron de la Moureyre C, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clinical pharmacology and therapeutics. 1997. Otterness D, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity. Proceedings of the National Academy of Sciences of the United States of America. 1997. Tai H L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Annals of internal medicine. 1997. Yates C R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Individualizing therapy with 6-mercaptopurine and 6-thioguanine related to the thiopurine methyltransferase genetic polymorphism. Therapeutic drug monitoring. 1996. Lennard L, et al. PubMed
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Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. American journal of human genetics. 1996. Tai H L, et al. PubMed
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A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proceedings of the National Academy of Sciences of the United States of America. 1995. Krynetski E Y, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia. Archives of disease in childhood. 1993. Lennard L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet. 1993. McLeod H L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The clinical pharmacology of 6-mercaptopurine. European journal of clinical pharmacology. 1992. Lennard L. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. The Journal of pediatrics. 1991. Evans W E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clinical pharmacology and therapeutics. 1989. Lennard L, et al. PubMed
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Thiopurine pharmacogenetics in leukemia: correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations. Clinical pharmacology and therapeutics. 1987. Lennard L, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-1005-01
DrugBank:
DB00993
ChEBI:
2948
KEGG Drug:
D00238
PubChem Compound:
2265
PubChem Substance:
46508252
9055
Drugs Product Database (DPD):
2242907
ChemSpider:
2178
Therapeutic Targets Database:
DAP000782
FDA Drug Label at DailyMed:
0a83e716-b688-433f-ac27-ae95132810cf

Clinical Trials

These are trials that mention azathioprine and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.