How does the TPMT enzyme affect an azathioprine drug?

How does the TPMT enzyme affect an azathioprine drug?

CONCLUSION. 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.

What is the importance of measuring TPMT in patients taking azathioprine?

At the start of azathioprine or mercaptopurine therapy, measurement of TPMT activity has a role in identifying the 1 in 300 patients who are at risk of severe myelosuppression when treated with standard thiopurine dosages.

What should you check before 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 is TPMT deficiency?

Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body’s immune system.

Why is TPMT important?

Therefore, the TPMT genetic polymorphism is a significant factor responsible for serious adverse drug reactions (myelosuppression) in patients treated with thiopurines and may also contribute to individual variation in therapeutic efficacy [Article:15784872].

Why is TPMT test done?

Though the TPMT test is used to predict risk of bone marrow toxicity, full blood counts (FBCs) should also be done at regular intervals to detect bone marrow toxicity during treatment with thiopurine drugs. The FBC is a common blood test that measures the number of red blood cells, white blood cells and platelets.

Where is TPMT located?

Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the TPMT gene. A pseudogene for this locus is located on chromosome 18q.

What is TPMT level?

Complete TPMT deficiency (TPMT <10 nmol/h/g Hb) indicates that there is an absolute intolerance to thiopurine drugs. Low activity indicates partial enzyme deficiency and therefore that the probability of azathioprine-induced bone marrow depression or nausea is HIGH.

What do high TPMT levels mean?

High TPMT activity: > 65 U/mL – Individuals are not predicted to be at low risk for bone marrow toxicity as a consequence of standard thiopurine dosing, but may be at risk for therapeutic failure due to excessive inactivation of thiopurine drugs.

Can a person with TPMT deficiency take 6-MP?

Adverse effects of azathioprine or 6-MP administration can be observed in individuals who are either homozygous or heterozygous for TPMT deficiency. As such, knowing a patient’s TPMT status prior to treatment with azathioprine or 6-MP is important for purposes of calculating drug dosages. Recent blood transfusions may mask a deficient TPMT result.

What are the effects of azathioprine on TPMT?

In the intolerant group, those experiencing neutropenia had significantly lower TPMT activities than those experiencing other toxicities (for example, pancreatitis, hepatitis, dermatological problems). Survival analysis, based on time to first relapse, was performed on a subgroup of patients taking low dose (<2.0 mg/kg) azathioprine.

What is the TPMT and NUDT15 genotype of azathioprine?

Azathioprine Therapy and TPMT and NUDT15 Genotype – Medical Genetics Summaries – NCBI Bookshelf Azathioprine (brand names Imuran, Azasan) is an immunosuppressant that belongs to the drug class of thiopurines.

What happens to thiopurine methyltransferase ( TPMT ) deficiency?

Thiopurine methyltransferase (TPMT) deficiency is a condition in which patients treated with standard doses of the immunosuppressant azathioprine or the antineoplastic drug 6-mercaptopurine (6-MP) may develop life-threatening myelosuppression or severe hematopoietic toxicity.

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