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Q. What test should be ordered to determine whether patients are at an increased risk for the severe side effects of the immunosuppressant azathioprine (Imuran) or the antineoplastic drug 6-mercaptopurine (6-MP, Purinethol)?
A. Patients with low thiopurine methyltransferase (TPMT) enzyme activity are at an increased risk for side effects associated with taking the standard dose of the immunosuppressant azathioprine (Imuran) or the antineoplastic drug 6-mercaptopurine (6-MP, Purinethol). Severe side effects include excessive myelosuppression or severe hematopoietic toxicity and can be fatal. Knowing a patient’s TPMT enzymatic activity prior to beginning drug therapy allows for individualization of the medication dosage, ensuring treatment is both effective and safe. Mayo Medical Laboratories offers #80291 Thiopurine Methyltransferase (TPMT), Erythrocytes, which quantifies the activity of TPMT enzyme in a patient’s blood and can, therefore, be used to determine the appropriate dosage of azathioprine or 6-mercaptopurine. Within the general population, 10% of individuals show intermediate TPMT enzyme activity while 1 in 300 persons has deficient TPMT enzyme activity. Patients with either intermediate or low enzyme activity should be treated accordingly to avoid the life-threatening side effects of azathioprine or 6-MP. While molecular confirmation is currently available, assessment of TPMT enzyme activity is the preferred first-line test. It is the phenotypic equivalent of TPMT genotyping, can be performed quickly, and is less costly than genotyping. Molecular testing looks only for specific common mutations known to result in decreased TPMT enzyme activity; it does not determine actual enzyme activity. Also, patients with new or rare mutations not included in these panels will be missed and will be at risk of developing the life-threatening complications associated with the azathioprine or 6-MP therapies.
Booth RA, Ansari MT, Loit E, et al: Assessment of thiopurine s-methyltransferase activity in patients prescribed thiopurines: a systematic review. Ann Intern Med 2011;154:814-823
Sandborn WJ: Pharmacogenomics and IBD: TPMT and Thiopurines. Inflamm Bowel Dis 2004;10 Suppl 1:S35-S37