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Thiopurines (TPMT and NUDT15) and medicines

 
 

When you take a medicine (drug), your body has to have a way to handle the medicine. One way is for enzymes to metabolize (break down) the medicine. Two enzymes in your body, called thiopurine methyltransferase (TPMT) and nudix-type motif 15 (NUDT15), break down a class of medicines called thiopurines. Thiopurines include mercaptopurine (6-MP, Purinethol®), azathioprine (Imuran®), and thioguanine (6-TG, Tabloid®). Mercaptopurine and thioguanine are important chemotherapy drugs used to treat leukemia. Azathioprine is a medicine that is used to treat a variety of autoimmune diseases. Like many medicines, how well they work and their side effects can be different from person to person.

Most people have no problem breaking down thiopurines. However, a small percentage of people have little or no ability to break down these medicines. People with no TPMT or no NUDT15 enzyme activity can have serious side effects (infection, anemia, or bleeding) if they receive normal doses of thiopurines. For these people, toxic levels of the medicine build up in the body and make blood counts too low.

Pharmacogenetic testing

DNA is like a set of instructions for your body that can help decide how well your enzymes will work. Each person differs from another at the DNA (gene) level. The parts of DNA that instruct how well the TPMT and NUDT15 enzymes work are called the TPMT gene and NUDT15 gene. The study of how differences in genes like TPMT and NUDT15 affect the way you break down medicines is called pharmacogenetics (FAR mah coh je NEH tiks).

By testing your DNA (with a pharmacogenetic test), we may find differences that can allow us to predict how well your TPMT and NUDT15 enzymes work. The results of this test will help your doctor choose the correct dose of medicine to give you if you need to take a thiopurine.

The differences in the TPMT and NUDT15 genes are not linked to each other. So, different people have different combined results of TPMT and NUDT15 enzyme activities. Overall, your combined results from the TPMT genetic test and NUDT15 genetic test will help guide your first dose of thiopurine medicines. Doses after the first one may change based on your blood counts.

  • Normal metabolizers of thiopurines – People in this group have normal TPMT activity (TPMT normal metabolizer) and normal or less active NUDT15 enzyme activity (NUDT15 normal metabolizer or intermediate metabolizer). Most people fall into this category. The initial starting dose of thiopurines is the normal dose for these patients.
  • Intermediate metabolizers of thiopurines –People in this group have less active TPMT enzyme activity (TPMT intermediate metabolizer) along with normal or less active NUDT15 enzyme activity (NUDT15 normal or intermediate metabolizer). About 10 percent of people fall into this category. They may require lower doses of thiopurine medicines to avoid side effects.
  • Poor metabolizers of thiopurines – People in this group have no TPMT enzyme activity (TPMT poor metabolizer) or no NUDT15 enzyme activity (NUDT15 poor metabolizer). About 1 percent of people fall into this category. These patients are at high risk of having side effects, including very low blood counts that could be life-threatening. These patients should receive much lower doses of thiopurines than normal metabolizers to avoid low blood counts.

Your doctor will use the information of both your TPMT and NUDT15 gene tests to choose the right dose of thiopurine medicines for you.

For more information about TPMTNUDT15 and thiopurines, please go to www.stjude.org/pg4kds or www.cpicpgx.org.

Questions?

If you have questions about pharmacogenetic testing at St. Jude, call one of the Pharmaceutical Sciences research nurses at 901-595-2482 or email pknurses@stjude.org. If you are calling from outside of the Memphis area, dial toll free 1-866-2ST-JUDE (1-866-278-5833), then dial extension 2482.


 

This document is not intended to take the place of the care and attention of your personal physician or other professional medical services. Our aim is to promote active participation in your care and treatment by providing information and education. Questions about individual health concerns or specific treatment options should be discussed with your physician.

St. Jude complies with health care-related federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex.

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