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Gastroenterol Hepatol. 2018 Mar;41(3):205-221. doi: 10.1016/j.gastrohep.2017.11.007. Epub 2018 Jan 19.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of thiopurines in inflammatory bowel disease.

[Article in English, Spanish]

Author information

1
Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España. Electronic address: fbermejos1@gmail.com.
2
Servicio de Digestivo, Hospital Universitari La Fe, Valencia, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España.
3
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicios de Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, España.
4
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Servicio de Digestivo, Hospital Universitari Germans Trias i Pujol, Badalona, España.
5
Servicio de Digestivo, Complejo Hospitalario Universitario de Ferrol, Ferrol, España.
6
Servicio de Digestivo, Hospital Universitari Santa Creu i Sant Pau, Barcelona, España.
7
Servicio de Digestivo, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, España.
8
Servicio de Digestivo, Hospital Universitario Ramón y Cajal, Madrid, España.

Abstract

Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects. Before they are prescribed, immunisation status against certain infections should be checked. Determination of thiopurine methyltransferase activity (TPMT) is not mandatory but it increases initial safety. The appropriate dose is 2.5mg/kg/day for azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and other types of hepatotoxicity), and their surveillance should never be interrupted during treatment. If therapy fails or adverse effects develop, management can include switching from one thiopurine to the other, reducing the dose, combining low doses of azathioprine with allopurinol and assessing metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use is safe during conception, pregnancy and breastfeeding.

KEYWORDS:

Azathioprine; Azatioprina; Colitis ulcerosa; Crohn's disease; Enfermedad de Crohn; Enfermedad inflamatoria intestinal; Inflammatory bowel disease; Mercaptopurina; Mercaptopurine; Metabolites; Metabolitos; Thiopurine; Tiopurina; Ulcerative colitis

PMID:
29357999
DOI:
10.1016/j.gastrohep.2017.11.007
[Indexed for MEDLINE]

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