Davis's Lab & Diagnostic Tests
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Immunosuppressants: Cyclosporine, Methotrexate, Everolimus, Sirolimus, and Tacrolimus

General

Synonym/Acronym:
Cyclosporine (Sandimmune), methotrexate (MTX, amethopterin, Folex, Rheumatrex), methotrexate sodium (Mexate), everolimus (Afinitor, Certican, Zortress), sirolimus (Rapamycin), tacrolimus (Prograf).

Common Use:
To monitor appropriate drug dosage of immunosuppressant related to organ transplant maintenance.

Specimen:
Whole blood (1 mL) collected in lavender-top tube for cyclosporine, everolimus; sirolimus; tacrolimus. Serum (1 mL) collected in a red-top tube for methotrexate; specimen must be protected from light.

ImmunosuppressantRoute of AdministrationRecommended Collection Time
CyclosporineOral or intravenous12 hr after dose or immediately prior to next dose
MethotrexateOralVaries according to dosing protocol
IntramuscularVaries according to dosing protocol
EverolimusOralImmediately prior to next dose
SirolimusOralImmediately prior to next dose
TacrolimusOralImmediately prior to next dose
Leucovorin therapy, also called leucovorin rescue, is used in conjunction with administration of methotrexate. Leucovorin, a fast-acting form of folic acid, protects healthy cells from the toxic effects of methotrexate.
Important note: This information must be clearly and accurately communicated to avoid misunderstanding of the dose time in relation to the collection time. Miscommunication between the individual administering the medication and the individual collecting the specimen is the most frequent cause of subtherapeutic levels, toxic levels, and misleading information used in calculation of future doses.

Normal Findings:
(Method: Immunoassay for cyclosporine and methotrexate; liquid chromatography with tandem mass spectrometry for everolimus, sirolimus, and tacrolimus)

Therapeutic DoseHalf-Life (hr)Volume of Distribution (L/kg)Protein Binding (%)Excretion
Conventional UnitsSI Units (Conventional Units × 0.832)
Cyclosporine100–300 ng/mL renal transplant83–250 nmol/L8–244–690Renal
200–350 ng/mL cardiac, hepatic, pancreatic transplant166–291 nmol/L8–244–690Renal
100–300 ng/mL bone marrow transplant83–250 nmol/L8–244–690Renal
MethotrexateDependent on therapeutic approach5–90.4–150–70Renal
Low dose: 0.5–1 micromol/L
High dose: Less than 5 micromol/L at 24 h; less than 0.5 micromol/L at 48 h; less than 0.1 micromol/L at 72 h
Conventional UnitsSI Units (Conventional Units × 0.832)
EverolimusTransplant: 3–8 ng/mL18–35 (kidney); 30–35 (liver)128–58975Biliary
Oncology: 5–10 ng/mL18–35128–58975Biliary
SirolimusMaintenance phase: renal transplant: 4–12 ng/mL; liver transplant: 12–20 ng/mL46–784–2092Biliary
TacrolimusMaintenance phase: renal transplant: 6–12 ng/mL; liver transplant: 4–10 ng/mL; pancreas transplant: 10–18 ng/mL; bone marrow transplant: 10–20 ng/mL10–141.599Biliary
Therapeutic targets for the initial phase post-transplantation are slightly higher than during the maintenance phase and are influenced by the specific therapy chosen for each patient with respect to coordination of treatment for other conditions and corresponding therapies. Therapeutic ranges for everolimus, sirolimus, and tacrolimus assume concomitant administration of cyclosporine and steroids.

Immunosuppressants: Cyclosporine, Methotrexate, Everolimus, Sirolimus, and Tacrolimus has been found in Davis's Lab & Diagnostic Tests

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