(Assayed daily, Monday to Friday)
Tacrolimus monitoring is recommended for all patients receiving immunosuppression with Prograf for preventing graft rejection or autoimmune-based disorders. The drug was previously known as FK506. A slow release formulation (Advagraf) was introduced in 2008 for once-daily dosing. Other formulations include Modigraf (granules designed for small doses in water) and Adoport (generic tacrolimus) both of which were introduced in 2010, and also Capexion, Tacni, and Vivadex.
|Turnaround:||>95% of samples are turned around within 24 h of receipt on weekdays. We aim to issue results by 4 pm on samples received by 1.30 pm and, depending on workload, by 5–6 pm for samples received up to 2.30 pm|
|Sample:||2 mL EDTA-anticoagulated whole blood just pre-dose (12 h / 24 h post-dose for twice / once daily dosing, respectively)|
|Method:||Liquid chromatography-tandem mass spectrometry|
|Principle:||Tacrolimus is measured in whole blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS) based on a method by Keevil et al. (Annals of Clinical Biochemistry 2002; 39: 487–492). Our validated method is rapid, requires only a small sample volume, and offers advantages over immunoassay methods (Brown et al., Clinical Chemistry 2005; 51: 586–592). The IDM laboratory participates in the International Proficiency Testing Scheme for tacrolimus.|
Immunosuppressive drugs require monitoring because they act within a narrow range of concentrations and show large inter-individual differences in drug handling and efficacy which make standard dosing regimens impractical. Therapy aims to suppress the immune system sufficiently to prevent graft rejection or autoimmune disease but without either acute toxicity (e.g. renal or gastrointestinal damage) or the increased generic risks of infection or malignancy. IDM provides the most valuable method for regulating dosage in these circumstances and because no real time measurement of “immunosuppression” exists. The principle is to adjust dosage on the basis of standardised drug level measurements that can be targeted to a therapeutic range appropriate for the individual patient. Such adjustments must be made in conjunction with clinical information and other laboratory test results. IDM therapeutic ranges may vary with:
The customary single blood sample used for monitoring is the trough drug level, determined just prior to dosage and at a constant interval from the time of the previous dose. Measurements at alternative times, e.g. 2 hours post dose (C2), may be useful in certain situations. For ciclosporin in particular, a C2 level might offer an improved estimate of total early drug exposure. However, it may be difficult to obtain accurately if dosage and phlebotomy times vary. Therapeutic ranges are higher for C2 than for trough drug levels because drug concentrations peak at around 2 h post dose. Contact the IDM Laboratory for more information if required.
Immunosuppressive drug concentrations may also be profoundly affected by:
In addition to use as an immunosuppressant, everolimus is being used as an antitumour drug and has been licensed for use in treating advanced renal cell carcinoma with the alternate trade name of Afinitor. Currently there is no information available on a suitable therapeutic range for these effects.
The frequency at which IDM is performed generally decreases with time after transplant. It is rarely necessary to monitor levels more than three times weekly e.g. Monday, Wednesday and Friday, because the half-lives of the immunosuppressants exceed 12 h. Consequently, drug levels will not re-equilibrate for 2–3 days after changes in dosage. However, immediately after transplantation, daily monitoring may be required in unstable (especially paediatric) patients but the frequency may decrease to once three or six monthly in long-term stable patients. The frequency of testing should be determined by any changes in likely modulators of drug levels, that is:
The examination of drug profiles during a dosage interval may be a valuable adjunct to conventional trough level monitoring. The additional information available from these pharmacokinetic studies may reveal unexpected abnormalities in the rate and extent of drug absorption and disposition.
|Turnaround: within 24hrs|
|Price: Contact Lab|
|IDM service: kch-tr.KCHIDMService@nhs.net|
|Therapeutic Ranges: (males = females)|
NB. These ranges are meant only as a guide and will need to be considered in
the context of clinical indications and any additional immunosuppressive therapy that is
12 – 18 µg/L (ng/mL) occasionally higher: