Sirolimus

Order Code

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5283

Preferred Specimen

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1 mL EDTA whole blood. Refrigerate.
Pre-dose (trough) level should be collected.

ContainerType

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EDTA (lavender top) tube

Minimum Volume

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0.3 mL whole blood

Transport Temperature

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Refrigerated

Expected Turnaround Time

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3-4 days

Specimen Stability

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1 day room temperature; 1 week refrigerated; 2 months frozen

Methodology

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High performance liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Rejection Criteria

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• Clotted samples
  serum
  plasma
  samples left at room temperature for more than 24 hours

Overview

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Sirolimus is a macrolide-class immunosuppressant used either alone or in combination with calcineurin inhibitors (such as tacrolimus or cyclosporine) and corticosteroids to prevent organ transplant rejection. While it is most frequently employed in kidney transplantation, sirolimus has also been used in heart and liver transplants, as well as in the prevention and treatment of graft-versus-host disease. Due to significant inter- and intra-patient pharmacokinetic variability—often influenced by disease states or co-administered immunosuppressants and other interacting medications—therapeutic drug monitoring is recommended to maintain target trough levels.

Clinical Significance

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Monitor blood level in management of immunosuppression for organ transplant recipients; optimize dose and minimize toxicity. Monitoring of blood levels is imperative as many factors including bioavailability, distribution, and coadministration of a number of drugs affect blood drug levels. Monitoring is particularly necessary in:

• Pediatric patients
• Patients ≥13 years of age weighing less than 40 kg
• Patients with hepatic impairment
• Patients on concurrent inhibitors or inducers of CYP3A4 or P-gp
• Concurrent cyclosporine dosing is markedly reduced or discontinued
• Change in sirolimus dosage form
• Dosing adjustment (measure levels 7-14 days post adjustment)

Additional Information

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• Half-life: 46–78 hours
• Volume of Distribution: 12 ± 8 L/kg
• Protein Binding: Approximately 92%, primarily to albumin
• Time to Peak Concentration:
  • Oral solution: 1–3 hours
  • Tablet: 1–6 hours
• Time to Steady State: Typically achieved within 5–7 days

Sirolimus is a naturally derived compound, originally isolated from Streptomyces hygroscopicus, a soil bacterium found in the Vai Atare region of Easter Island. In transplant medicine, it is commonly administered with cyclosporine and corticosteroids, especially in renal transplantation. Unlike calcineurin inhibitors (cyclosporine and tacrolimus), sirolimus targets a different intracellular pathway. Its primary mechanism involves inhibition of the mammalian target of rapamycin (mTOR), a key regulator of the cell cycle. This results in suppression of cytokine-driven T-cell proliferation by arresting cell progression from the G1 to the S phase.

Metabolized primarily in the liver via the cytochrome P450 enzyme CYP3A4 and P-glycoprotein (P-gp), sirolimus undergoes O-demethylation and hydroxylation to produce several metabolites. While these can be detected in whole blood, the parent compound accounts for over 90% of immunosuppressive activity. Fecal excretion is the predominant elimination route (>90%), with minimal renal clearance (<5%). The drug is primarily found in red blood cells (~95%), with lesser concentrations in plasma and other blood components. Due to its high red cell partitioning (blood-to-plasma ratio ~30:1), whole blood is the preferred matrix for monitoring.

Drug Interactions

Medications/Substances That May Increase Sirolimus Levels:

• 5-Aminosalicylic Acid Derivatives
• Abametapir
• Anti-hepatitis C Virus (HCV) Combination Therapies
• Cannabidiol
• Chloramphenicol (Ophthalmic)
• Cladribine
• Clofazimine
• Clotrimazole (Oral and Topical)
• Cyclosporine (Systemic)
• CYP3A4 Inhibitors (Strong, Moderate, Weak)
• Dipyrone
• Erdafitinib
• Erythromycin (Systemic)
• Fexinidazole
• Fluconazole
• Fusidic Acid (Systemic)
• GI Prokinetic Agents
• Grapefruit Juice
• Lasmiditan
• Micafungin
• P-gp/ABCB1 Inhibitors
• Posaconazole
• Promazine
• Solriamfetol
• Spironolactone
• Tacrolimus (Systemic and Topical)
• Voriconazole
• Live Vaccines

Medications/Substances That May Decrease Sirolimus Levels:

• CYP3A4 Inducers (Strong, Moderate, Weak)
• Echinacea
• Erdafitinib
• Ivosidenib
• Rifabutin
• Live Vaccines

Adverse Effects

Common side effects include:

• Hyperlipidemia
• Leukopenia
• Thrombocytopenia

Other reported effects may include hypertension, anemia, gastrointestinal disturbances (e.g., diarrhea), and dermatologic reactions such as rash.

References

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Alias

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• Rapamune
• Rapamycin

Test Setup Days

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Sunday through Saturday AM shift

CPT

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80195 Laboratory Developed Test By ARUP.
LOINC: 29247-4

Reference Range

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THERAPEUTIC: 4-12 NG/ML
TOXIC: >25 NG/ML

UNIT CODE	UNIT CODE NAME	ANALYTE	GENDER	AGE	REFERENCE RANGE	Units of Measure
5283	SIROLIMUS	SIRO	NOT SPECIFIED	ALL
5283	SIROLIMUS	SIRO	MALE	ALL
5283	SIROLIMUS	SIRO	FEMALE	ALL