TPMT testing

Prior to starting a patient on azathioprine (Imuran) or 6-mercaptopurine (6-MP)(Purinethol) test for TPMT activity

Reference Range:

TPMT Activity
 Value (U/mL) Interpretation
Normal
 25-65
 Individuals are predicted to be at low risk of bone marrow toxicity as a consequence of standard thiopurine therapy; no dose adjustment is recommended
Abnormal
 < 25
 Individuals are predicted to be at high risk of bone marrow toxicity as a consequence of standard thiopurine dosing; a dose reduction and therapeutic monitoring is recommended.
High
 > 65
 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. Individuals may require higher than the standard dose; therapeutic monitoring is recommended.

Interpretive Data:
The TPMT, RBC assay is used as a screen to detect individuals with low (abnormal) TPMT activity that may be at risk for excessive myelosuppression when exposed to standard doses of thiopurines such as azathioprine (Imuran) and 6-mercaptopurine (6-MP)(Purinethol). TPMT is the primary metabolic route for inactivation of thiopurine drugs in the bone marrow. When TPMT activity is low, it is predicted that proportionately more 6-mercaptopurine is converted into the cytotoxic 6- thioguanine nucleotides, which will accumulate in the bone marrow and cause excessive toxicity. The activity of TPMT is measured by the nanomoles of 6-methylmercaptopurine (inactive metabolite) produced per 1 mL of packed red blood cells, (U/mL).

TPMT phenotype testing does not replace the need for clinical monitoring of patients treated with thiopurine drugs. Genotype for TPMT cannot be inferred from TPMT activity (phenotype). Phenotype testing should not be requested for patients currently treated with thiopurine drugs, as results will be falsely low. Current TPMT phenotype may not reflect future TPMT phenotype, particularly in patients who received blood transfusion within 30-60 days of testing. TPMT enzyme activity can be inhibited by several drugs such as: naproxen (Aleve®), ibuprofen (Advil®, Motrin®), ketoprofen (Orudis®), furosemide (Lasix®), sulfasalazine (Azulfidine®), mesalamine (Asacol®), olsalazine (Dipentum®), mefenamic acid (Ponstel®), thiazide diuretics, and benzoic acid inhibitors.

TPMT inhibitors may contribute to falsely low results; patients should abstain from these drugs for at least 48 hours prior to TPMT testing. Falsely low results may also occur as a result of inappropriate specimen handling.


TPMT Monitoring

6-TGN

Suboptimal dosing
 <235      pmol 6-TGN/8×108 red blood cells
Optimal Dosing
 235-400 pmol 6-TGN/8×108 red blood cells
Risk of myelosuppression
 >450      pmol 6-TGN/8×108 red blood cells


6-MMPN

Risk of Hepatotoxicity
 >5700   pmol 6-TGN/8×108 red blood cells





References
https://www.healthcare.uiowa.edu/path_handbook/handbook/test3096.html
https://www.labcorp.com/tests/503800/thiopurine-metabolites
Chevaux JB, Peyrin-Biroulet L, Sparrow MP. Optimizing thiopurine therapy in inflammatory bowel disease. Inflamm Bowel Dis. 2011 Jun; 17(6):1428-1435.