Increased liver enzyme levels during azathioprine treatment: Beware of concomitant use of proton pump inhibitors

J. Van Der Schaft; R. H N Van Schaik; M. P H Van Den Broek; C. A F M Bruijnzeel-Koomen; M. S. De Bruin-Weller

doi:10.1111/bjd.14006

Increased liver enzyme levels during azathioprine treatment: Beware of concomitant use of proton pump inhibitors

J. Van Der Schaft, R. H N Van Schaik, M. P H Van Den Broek, C. A F M Bruijnzeel-Koomen, M. S. De Bruin-Weller

Research output: Contribution to journal › Letter › Academic › peer-review

Abstract

Azathioprine (AZA) is a purine antagonist, which is frequently used off label in chronic inflammatory skin diseases. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) influence the metabolism of AZA. A reduced enzymatic activity of TMPT is associated with increased 6-thioguaninie nucleotide (6-TGN) levels which may cause severe leukopenia. High TPMT activity is associated with increased 6-methylmercaptopurine (6-MMP) levels (toxic 6-MMP >5700 pmol/8x10(8) RBCs), which is associated with liver toxicity.(1) Alanine transaminase (ALT) >3 upper limits of normal has been identified as a sensitive, but not necessarily specific signal of liver toxicity.(2) In daily practice AZA is often started with a test dose of 50 mg/day for 1-2 weeks. If laboratory tests show no abnormalities, the dose is increased to up to 150-200 mg/day. This article is protected by copyright. All rights reserved.

Original language	English
Pages (from-to)	1338-1339
Number of pages	2
Journal	British Journal of Dermatology
Volume	173
Issue number	5
DOIs	https://doi.org/10.1111/bjd.14006 https://doi.org/10.1111/bjd.14006
Publication status	Published - 1 Nov 2015

Keywords

SEVERE ATOPIC ECZEMA
DOUBLE-BLIND
TRIAL

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@article{281b3e2809f14bc28f10151246ab1911,

title = "Increased liver enzyme levels during azathioprine treatment: Beware of concomitant use of proton pump inhibitors",

abstract = "Azathioprine (AZA) is a purine antagonist, which is frequently used off label in chronic inflammatory skin diseases. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) influence the metabolism of AZA. A reduced enzymatic activity of TMPT is associated with increased 6-thioguaninie nucleotide (6-TGN) levels which may cause severe leukopenia. High TPMT activity is associated with increased 6-methylmercaptopurine (6-MMP) levels (toxic 6-MMP >5700 pmol/8x10(8) RBCs), which is associated with liver toxicity.(1) Alanine transaminase (ALT) >3 upper limits of normal has been identified as a sensitive, but not necessarily specific signal of liver toxicity.(2) In daily practice AZA is often started with a test dose of 50 mg/day for 1-2 weeks. If laboratory tests show no abnormalities, the dose is increased to up to 150-200 mg/day. This article is protected by copyright. All rights reserved.",

keywords = "SEVERE ATOPIC ECZEMA, DOUBLE-BLIND, TRIAL",

author = "{Van Der Schaft}, J. and {Van Schaik}, {R. H N} and {Van Den Broek}, {M. P H} and Bruijnzeel-Koomen, {C. A F M} and {De Bruin-Weller}, {M. S.}",

year = "2015",

month = nov,

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doi = "10.1111/bjd.14006",

language = "English",

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journal = "British Journal of Dermatology",

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TY - JOUR

T1 - Increased liver enzyme levels during azathioprine treatment

T2 - Beware of concomitant use of proton pump inhibitors

AU - Van Der Schaft, J.

AU - Van Schaik, R. H N

AU - Van Den Broek, M. P H

AU - Bruijnzeel-Koomen, C. A F M

AU - De Bruin-Weller, M. S.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Azathioprine (AZA) is a purine antagonist, which is frequently used off label in chronic inflammatory skin diseases. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) influence the metabolism of AZA. A reduced enzymatic activity of TMPT is associated with increased 6-thioguaninie nucleotide (6-TGN) levels which may cause severe leukopenia. High TPMT activity is associated with increased 6-methylmercaptopurine (6-MMP) levels (toxic 6-MMP >5700 pmol/8x10(8) RBCs), which is associated with liver toxicity.(1) Alanine transaminase (ALT) >3 upper limits of normal has been identified as a sensitive, but not necessarily specific signal of liver toxicity.(2) In daily practice AZA is often started with a test dose of 50 mg/day for 1-2 weeks. If laboratory tests show no abnormalities, the dose is increased to up to 150-200 mg/day. This article is protected by copyright. All rights reserved.

AB - Azathioprine (AZA) is a purine antagonist, which is frequently used off label in chronic inflammatory skin diseases. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) influence the metabolism of AZA. A reduced enzymatic activity of TMPT is associated with increased 6-thioguaninie nucleotide (6-TGN) levels which may cause severe leukopenia. High TPMT activity is associated with increased 6-methylmercaptopurine (6-MMP) levels (toxic 6-MMP >5700 pmol/8x10(8) RBCs), which is associated with liver toxicity.(1) Alanine transaminase (ALT) >3 upper limits of normal has been identified as a sensitive, but not necessarily specific signal of liver toxicity.(2) In daily practice AZA is often started with a test dose of 50 mg/day for 1-2 weeks. If laboratory tests show no abnormalities, the dose is increased to up to 150-200 mg/day. This article is protected by copyright. All rights reserved.

KW - SEVERE ATOPIC ECZEMA

KW - DOUBLE-BLIND

KW - TRIAL

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DO - 10.1111/bjd.14006

M3 - Letter

C2 - 26139089

SN - 0007-0963

VL - 173

SP - 1338

EP - 1339

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 5

ER -

Increased liver enzyme levels during azathioprine treatment: Beware of concomitant use of proton pump inhibitors

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Keywords

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