Why is it important to check TPMT levels before commencing azathioprine?
Why is it important to check TPMT levels before commencing azathioprine?
The activity level of the TPMT enzyme, or the genetics underlying the enzyme’s activity, is tested before thiopurine drug therapy to make sure that individuals treated with the drugs can metabolize them. Examples of thiopurines include azathioprine, mercaptopurine, and thioguanine.
How does the TPMT enzyme affect an azathioprine drug?
Several published studies indicate that patients with reduced TPMT or NUDT15 activity receiving usual doses of 6-MP or azathioprine, accumulate excessive cellular concentrations of active 6-TGNs, and are at higher risk for severe myelosuppression.
What should be monitored while taking azathioprine?
Regular blood tests during treatment Taking azathioprine can sometimes affect your liver, kidneys or bone marrow. You will have blood tests to check your liver function, kidney function and blood count before you start taking this medicine.
What is a low TPMT level?
If someone’s TPMT activity is too low, the person may not effectively metabolize thiopurines, which can lead to severe side effects. About one person in every 300 is severely deficient in TPMT, and about 10% of the population in the U.S. has lower than normal levels of TPMT.
What causes a low TPMT level?
TPMT deficiency results from changes in the TPMT gene. This gene provides instructions for making the TPMT enzyme, which plays a critical role in breaking down (metabolizing) thiopurine drugs. Once inside the body, these drugs are converted to toxic compounds that kill immune system cells in the bone marrow.
What is thiopurine methyltransferase ( TPMT ) in azathioprine?
Thiopurine methyltransferase (TPMT) is an enzyme involved in the metabolism of the immunosuppressant drugs azathioprine and mercaptopurine. Up to 6 in every 1,000 people have inherited deficiency of this enzyme and so are at risk of potentially fatal bone marrow suppression from these drugs.
Can a person with TPMT deficiency take AZA?
Thiopurine methyltransferase (TPMT) is the main enzyme responsible for inactivating toxic products of azathioprine (AZA) metabolism. Patients with homozygous deficiency of this enzyme have no enzyme activity and ideally should not be given AZA.
When to use tpmtgenotyping before Azathioprine treatment?
The FDA recommends TPMTgenotyping or phenotyping before starting treatment with azathioprine. This allows patients who are at increased risk for toxicity to be identified and for the starting dose of azathioprine to be reduced, or for an alternative therapy to be used (1).
How are active metabolites of azathioprine metabolized?
The active metabolites are metabolized and inactivated by the enzyme thiopurine methyltransferase (TPMT) and the enzyme nudix hydrolase 15 (NUDT15).
