Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine
Open Access
- 1 January 2003
- Vol. 52 (1) , 140-142
- https://doi.org/10.1136/gut.52.1.140
Abstract
Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn’s disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.Keywords
This publication has 19 references indexed in Scilit:
- 6-Thioguanine: a naked bullet? (Or how pharmacogenomics can make old drugs brand new).Inflammatory Bowel Diseases, 2001
- Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel diseaseGut, 2001
- Rational dosing of azathioprine and 6-mercaptopurineGut, 2001
- Pharmacogenetics and adverse drug reactionsThe Lancet, 2000
- Pharmacogenomics: The promise of personalized medicineAAPS PharmSci, 2000
- A Simple Classification of Crohnʼs Disease: Report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998Inflammatory Bowel Diseases, 2000
- Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiencyActa Paediatrica, 1998
- Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipientThe Lancet, 1993
- 6-Mercaptopurine: Cytotoxicity and biochemical pharmacology in human malignant T-lymphoblastsBiochemical Pharmacology, 1993
- Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemiaThe Journal of Pediatrics, 1991