From the Guidelines
TPMT testing is necessary for patients on certain drugs, such as azathioprine and mercaptopurine, to prevent potentially life-threatening side effects. These medications are commonly used to treat conditions like inflammatory bowel disease, rheumatoid arthritis, and certain types of cancer. TPMT, or thiopurine methyltransferase, is an enzyme that breaks down these drugs in the body. Some people have low or absent TPMT activity, which can lead to toxic levels of the medication building up in the body. Testing for TPMT activity before starting these medications helps doctors determine the appropriate dose and monitor for potential side effects, such as bone marrow suppression and liver damage.
- Key points to consider:
- Patients with low TPMT activity are at increased risk of discontinuing thiopurines due to adverse effects 1
- Testing for TPMT activity can help identify patients who require a lower dose of azathioprine, typically 25-50% of the standard dose, and close monitoring of their blood counts and liver function 1, 2
- The frequency of low TPMT activity in the general population is approximately 0.3%, and the presence of deficiency alleles does not preclude tolerance of the drug 3, 4
- Routine pre-treatment TPMT testing can provide reassurance about the absence of a pre-existent risk for serious azathioprine toxicity, especially in centers where TPMT testing is readily available 5, 6
- Close monitoring of all patients started on azathioprine is mandatory, even following TPMT activity testing, as azathioprine toxicity is more frequently encountered in the absence of TPMT deficiency 6, 7
- Important considerations for clinical practice:
- Pretreatment testing of TPMT activity identifies those rare patients with zero or near-zero TPMT activity who are at risk for severe myelosuppression when treated with AZA 7
- Patients with heterozygous TPMT deficiency may require a 50% dose reduction of thiopurines to improve tolerance 1, 2
- The use of low doses of azathioprine with careful monitoring of metabolites in the blood may help avoid toxicity in patients with inflammatory bowel disease 6
From the FDA Drug Label
Patients with TPMT and/or NUDT Deficiency: Consider testing for TPMT and NUDT15 deficiency in patients who experience severe bone marrow toxicities Myelosuppression: Monitor complete blood count (CBC) and adjust the dose of Mercaptopurine Tablets for excessive myelosuppression Consider testing in patients with severe myelosuppression or repeated episodes of myelosuppression for thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency.
Thiopurine methyltransferase (TPMT) testing is needed for patients on certain drugs, such as azathioprine and mercaptopurine, to identify individuals with TPMT deficiency. This is because patients with TPMT deficiency are at a higher risk of severe bone marrow toxicities and myelosuppression when taking these drugs. Testing for TPMT deficiency can help guide dose adjustments and prevent toxicities 8, 9.
- Homozygous deficiency in TPMT may require alternative therapies or dose reduction.
- Heterozygous deficiency in TPMT may require dosage reduction.
From the Research
Importance of TPMT Testing
TPMT testing is necessary for patients on certain drugs, such as azathioprine and 6-mercaptopurine, due to the risk of severe bone marrow toxicity associated with TPMT deficiency 10, 11, 12, 13. The testing helps identify individuals with low or absent TPMT activity, who are at a higher risk of developing life-threatening myelosuppression.
Risk of Myelosuppression
- Patients with homozygous TPMT deficiency have no enzyme activity and are at a high risk of developing severe myelosuppression 12.
- Those with heterozygous TPMT deficiency have intermediate enzyme activity and are at an increased risk of developing myelosuppression 11.
- TPMT testing can help identify these individuals and allow for dose adjustment or alternative treatment options to minimize the risk of myelosuppression.
Benefits of TPMT Testing
- TPMT testing can help optimize thiopurine use and reduce the risk of adverse reactions 10.
- It can also aid in dose individualization and help distinguish between non-compliance, under-dosing, and thiopurine-resistant or refractory disease 10.
- The testing is cost-effective and can help identify TPMT-deficient individuals prior to the start of thiopurine therapy, reducing the risk of life-threatening toxicity 11.