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HelpTest Code SIIRO Sirolimus, Whole Blood
Reporting Name
Sirolimus, BUseful For
Monitoring whole blood sirolimus concentration during therapy, particularly in individuals coadministered cytochrome P450 (CYP) 3A4 substrates, inhibitors, or inducers
Adjusting dose to optimize immunosuppression while minimizing toxicity
Evaluating patient compliance
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
Whole Blood EDTASpecimen Required
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Draw blood immediately before a scheduled dose.
2. Do not centrifuge.
3. Send whole blood specimen in original tube. Do not aliquot.
Additional Information: Therapeutic range applies to trough specimen collected immediately prior to a.m. dose.
Specimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole Blood EDTA | Refrigerated (preferred) | 28 days | |
| Ambient | 28 days | ||
| Frozen | 28 days |
Reference Values
4-20 ng/mL (Trough)
Target steady-state trough concentrations vary depending on the type of transplant, concomitant immunosuppression, clinical/institutional protocols, and time post-transplant. Results should be interpreted in conjunction with this clinical information and any physical signs/symptoms of rejection/toxicity.
Day(s) Performed
Monday through Sunday
CPT Code Information
80195
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| SIIRO | Sirolimus, B | 29247-4 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 35144 | Sirolimus, B | 29247-4 |
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.Clinical Information
Sirolimus is a macrolide antibiotic, isolated from Streptomyces hygroscopicus, with potent effects, including suppression of T- and B-cell proliferation and antineoplastic and antifungal activity. It inhibits the protein kinase mTOR (mechanistic target of rapamycin) to arrest the cell cycle; it has no effects on calcineurin and, therefore, can either be used in addition to cyclosporine or tacrolimus or as a substitute in patients intolerant to these drugs.
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Sirolimus is metabolized by cytochrome P450 (CYP) 3A4; thus, blood concentrations are affected by drugs that inhibit or induce this enzyme. The pharmacokinetic interaction between sirolimus and cyclosporine or tacrolimus increases both therapeutic immunosuppression and the toxicity of these agents; lower doses are required with combined use. Adverse effects of sirolimus are generally concentration dependent, making therapeutic drug monitoring essential.
The frequency of monitoring trough concentrations varies on the indication. For example, for kidney transplant recipients, sirolimus is commonly measured at least 3 to 4 days after a loading dose or, if the kidney transplant recipient is receiving cyclosporin, between 5 to 7 days after initiation. Target concentrations vary depending on concomitant therapy, time posttransplant, the desired degree of immunosuppression, and adverse effects. When given with cyclosporine or tacrolimus, the therapeutic range for sirolimus is generally between 4 and 12 ng/mL with minimal added benefit for concentrations greater than10 ng/mL. When sirolimus is given without calcineurin inhibitors, higher trough levels are needed, usually 12 to 20 ng/mL but occasionally up to 20 to 30 ng/mL.
Interpretation
Most individuals display optimal response to sirolimus with trough whole blood levels 4 to 20 ng/mL. Preferred therapeutic ranges may vary by transplant type, protocol, and comedications.
Therapeutic ranges are based on specimens collected at trough (ie, immediately before a scheduled dose). Higher results will be obtained when the blood is collected at other times.
The assay is specific for sirolimus; it does not cross-react with cyclosporine, cyclosporine metabolites, tacrolimus, tacrolimus metabolites, or sirolimus metabolites. Results by liquid chromatography with detection by tandem mass spectrometry are approximately 30% less than by immunoassay.
Cautions
The recommended therapeutic range applies to trough specimens collected immediately before a dose. Blood drawn at other times will yield higher results.
Clinical Reference
1. Milone MC, Shaw LM: Therapeutic drugs and their management. In: Rifai N, Chiu RWK, Young I, Burnham CAD, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023:420-453
2. Kahan BD. Ten years of mTOR inhibitor therapy. Transplant Proc. 2003;35(3A):3S-240S
3. Yakupoglu YK, Kahan BD. Sirolimus: a current perspective. Exp Clin Transplant 2003;1(1):8-18
4. Groth CG, Backman L, Morales JM, et al. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation. 1999;67(7):1036-1042
Method Description
Blood specimens are subjected to protein precipitation. The resulting supernatant is analyzed by liquid chromatography tandem mass spectrometry.(Pablo AH, Breaud AR, Clarke W. Analysis of immunosuppressant drugs in whole blood by liquid chromatography-tandem mass spectrometry [LC-MS/MS]. Curr Protoc Toxicol. 2020;84(1):e92. doi:10.1002/cptx.92)
Report Available
Same day/1 to 3 daysSpecimen Retention Time
14 daysReject Due To
| Gross hemolysis | OK |
| Gross lipemia | OK |
| Gross icterus | OK |
| Clotted specimens | Reject |
Method Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Forms
If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-Renal Diagnostics Test Request (T830)
-Therapeutics Test Request (T831)