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Thiopurine methyltransferase (TPMT) is an enzyme that breaks down (metabolizes) thiopurines. Thiopurines include three medications: 6- mercaptopurine (6-MP), 6-thioguanine (6-TG), and azathioprine (see this link http://www.pharmgkb.org/search/annotatedGene/tpmt/index.jsp. 6-MP and 6-TG are often used to treat leukemia or lymphoma. Like many drugs, their effectiveness and side effects can vary from person to person. One of the reasons why this difference occurs is because each person’s ability to metabolize thiopurines is different based on variations in the TPMT gene. Every person can be classified into one of 3 possible genotype groups. We use a different starting dose of 6-MP and 6-TG for the different genotype groups. By changing the dose based on a patient’s genotype, there are fewer side effects (due to low blood counts).
Azathioprine: Consider reducing the dose of azathioprine to 0.6 to 2 mg/kg/day.
Mercaptopurine: Consider starting mercaptopurine doses at 30 to 70% of the normal dose.
Thioguanine: Consider starting thioguanine doses at 30 to 50% of the normal dose.
Azathioprine: Consider an alternative agent or reducing the dose of azathioprine by 90% and administer three times per week instead of daily.
Mercaptopurine: For non-malignant conditions, consider alternative agents; for malignancy, reduce the dose of mercaptopurine by 90% and administer three times per week instead of daily.
Thioguanine: Consider an alternative agent or reducing the dose of thioguanine by 90% and administer three times per week instead of daily.
More information for patients...
More information for healthcare professionals, visit www.pharmGKB.org.