From the Guidelines
To check tacrolimus levels, order a "Tacrolimus Blood Level" test, which is a specific immunoassay that measures the concentration of tacrolimus in whole blood, as recommended by the American College of Chest Physicians evidence-based clinical practice guidelines 1. This test requires a whole blood sample collected in an EDTA (purple-top) tube, not serum or plasma. The blood should be drawn immediately before the next scheduled dose, known as a trough level, to ensure consistent interpretation of results. Most transplant centers aim for specific target ranges depending on the type of organ transplant, time since transplantation, and individual patient factors, with recommended trough levels after lung transplantation ranging between 5 and 15 ng/mL 1. Tacrolimus has a narrow therapeutic window, with levels that are too low risking organ rejection and levels that are too high causing toxicity including nephrotoxicity, neurotoxicity, and increased infection risk. The sample should be processed promptly and kept at the appropriate temperature as specified by your laboratory, as improper handling can affect results. Regular monitoring is essential as tacrolimus levels can be affected by many factors including drug interactions, liver function, and dietary changes, and should be monitored closely whenever medications that inhibit or accelerate CYP3A4-mediated clearance of tacrolimus are added to or withdrawn from a patient’s medication regimen 1. Some key points to consider when monitoring tacrolimus levels include:
- Monitoring frequency: daily until a steady level is attained, then every 2 to 3 days until hospital discharge, with intervals gradually increased to every 1 to 2 weeks in the first 1 to 2 months posttransplant, and every 1 to 2 months once stable levels are attained 1
- Additional monitoring: intermittent measurement of serum potassium and glucose levels, renal function, and hepatic function, as well as CBC count to detect significant bone marrow suppression, at least every 4 to 6 weeks 1
From the FDA Drug Label
Whole blood is the matrix of choice and specimens should be collected into tubes containing ethylene diamine tetraacetic acid (EDTA) anticoagulant. To draw for tacrolimus level, a whole blood sample should be collected in tubes containing EDTA anticoagulant 2.
From the Research
Tacrolimus Level Measurement
To measure tacrolimus levels, whole blood is typically used due to its high red blood cell transfer rate of 95% 3.
Laboratory Tests
The following laboratory tests can be used to measure tacrolimus levels:
- Microparticle enzyme immunoassay (MEIA II) 4
- Enzyme multiplied immunoassay technique (EMIT) 4
- Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) 5
- High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) 6
- Liquid chromatography-mass spectrometry 7
Factors Affecting Tacrolimus Concentration
Several factors can affect tacrolimus concentration, including:
- Hematological parameters such as hematocrit, hemoglobin, red blood cell count, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, red cell distribution width, and platelet count 4
- Red blood cell transfusion 3
- Patient characteristics such as genotype (CYP3A4/5, ABCB1, NR1I2) 7
- Bioavailability 6
Key Considerations
When measuring tacrolimus levels, it is essential to consider the potential impact of these factors on the accuracy of the results. For example, the EMIT method may be preferred over the MEIA II method in anemic transplant patients 4. Additionally, individualized dosing based on measured concentrations may be futile due to high variability in bioavailability 6.