What percentage of the population has normal or high TPMT activity?
Approximately 89%–90% of the general Caucasian population has high (normal) TPMT activity, which corresponds with homozygous expression of TPMT∗1. Approximately 17 allelic variants of TPMT have been identified.
What is the normal range for TPMT?
Reference Interval
Normal TPMT activity: 24.0-44.0 U/mL – Individuals are predicted to be at low risk of bone marrow toxicity (myelosuppression) as a consequence of standard thiopurine therapy; no dose adjustment is recommended.
What causes TPMT levels to be low?
Causes. 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 does low TPMT activity mean?
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.
Should we test TPMT enzyme levels before starting azathioprine?
We describe a patient with homozygous deficiency of TPMT who developed life threatening neutropenic sepsis, and advocate that all patients should be tested for TPMT activity prior to starting AZA therapy.
Why is it important to check TPMT levels before commencing azathioprine?
Knowledge of the levels of TPMT enzyme activity would serve as a guide to clinicians prior to starting AZA and would also prevent potentially life threaten- ing bone marrow aplasia in patients with reduced enzyme activity.
What should be checked before starting azathioprine?
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. From week 1 to week 8 of your treatment you’ll have blood tests every week.
What tests should be done before starting azathioprine?
Testing TPMT activity before starting azathioprine can identify people who are TPMT deficient and who should not receive the drug.
Is azathioprine a high risk medication?
Azathioprine may increase your risk of developing certain types of cancer, especially skin cancer and lymphoma (cancer that begins in the cells that fight infection). If you have had a kidney transplant, there may be a higher risk that you will develop cancer even if you do not take azathioprine.
How long can you be on azathioprine?
How long will I be taking it? If tolerated, you will probably be on azathioprine for up to 5 years. Do not stop taking your medicine unless your doctor tells you to, even if you feel well.
How long can you stay on azathioprine?
If tolerated, you will probably be on azathioprine for up to 5 years. Do not stop taking your medicine unless your doctor tells you to, even if you feel well.
How often should you have blood tests on 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. From week 1 to week 8 of your treatment you’ll have blood tests every week.
Is azathioprine a black box warning?
Azathioprine has a “black box” warning—the strongest warning on a drug label—saying that the drug may increase the risk of certain types of cancer, including skin cancer and T cell lymphoma in people who have Crohn’s disease or ulcerative colitis.
How toxic is azathioprine?
Conclusions: From this study, it was estimated at 6% the risk of toxicity by the administration of azathioprine and 6-mercaptopurine to patients in Joinville.
Which is worse methotrexate or azathioprine?
Conclusions: This study confirms that methotrexate is effective in inducing remission in patients with chronic active Crohn’s disease, therapeutic efficacy being comparable, but not faster, than that of azathioprine.
What is the alternative to azathioprine?
Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies | Journal of Neurology, Neurosurgery & Psychiatry.
What are the long term effects of taking azathioprine?
The main theoretical risks of prolonged use would be the myelotoxicity, hepatotoxicity, and the development of cancer. In fact, serious bone marrow suppression or serious liver damage are uncommon, and can be minimized with proper use of the drug.