Immunosuppressive Drug Optimization and Monitoring - Organ Transplantation Drugs

Organ transplantation is the strategy of choice for end-stage organ disease. Immunosuppressive therapies have allowed patients to extend the life of the organ but require careful monitoring to prevent toxicity and rejection. Therapeutic choice should be carefully considered based on the clinical setting, and blood levels should be carefully monitored for adequate dosing and toxicity. Important factors include the organ transplanted, time posttransplant, age and clinical status of the patient, metabolic pathways, liver and kidney function, and concomitant medications.

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Immunosuppressant dose optimization
Failure to respond to immunosuppressants
Signs or symptoms consistent with inadequate immunosuppression
Signs or symptoms of immunosuppressant toxicity
Changes to concomitant medications
Change in kidney function, liver function, or other conditions that affect drug concentrations
Change to generic form of medication

Laboratory Testing

Whole blood specimens are used for therapeutic drug monitoring (TDM) of immunosuppressive drugs due to drug accumulation in red blood cells (RBCs) (serum/plasma not acceptable), including
- Cyclosporine A
- Tacrolimus
- Everolimus
- Sirolimus
- Thiopurine

Immunosuppressive drug tests

Immunosuppressive Drug Tests
ARUP Test	Indications	Therapeutic Range^a/Toxic Level
Cyclosporine A by Tandem Mass Spectrometry 0070035	Optimize drug therapy and monitor patient adherence	Therapeutic range – 100-400 ng/mL Kidney transplant (in combination with everolimus) 1 mo post transplant – 100-200 ng/mL 2-3 mos post transplant – 75-150 ng/mL 4-5 mos post transplant – 50-100 ng/mL 6-12 mos post transplant – 25-50 ng/mL Heart transplant Up to 3 mos post transplant – 350-525 ng/mL ≥4 mos post transplant – 145-350 ng/mL Liver transplant – 290-525 ng/mL Toxic – >700 ng/mL
Cyclosporine A, 2-Hour Post Dose (C2) by Tandem Mass Spectometry 0058902	Optimize drug therapy and monitor patient adherence	Renal transplant (suggested target range) – 800-1700 ng/mL Liver transplant (suggested target range) – 600-1000 ng/mL
Everolimus by Tandem Mass Spectrometry 0092118	Optimize drug therapy and monitor patient adherence	Kidney transplant (in combination with cyclosporine) – 3-8 ng/mL Liver transplant (in combination with tacrolimus) – 3-8 ng/mL Toxic value – >15 ng/mL
Leflunomide Metabolite, Serum or Plasma 2007460	Therapeutic monitoring and evaluating full elimination of the drug (eg, toxicity, pregnancy)	Therapeutic range – >40.000 µg/mL Toxic – not well established
Mycophenolic Acid and Metabolites 2010359	Optimize drug therapy and monitor patient adherence	Mycophenolic acid Therapeutic range – 1-3.5 µg/mL Toxic – >25 µg/mL Mycophenolic acid glucuronide Therapeutic range – 35-100 µg/mL Toxic – not well established Mycophenolic acid acyl-glucuronide Therapeutic range – not well established Toxic – not well established
Sirolimus by Tandem Mass Spectrometry 0098467	Optimize drug therapy and monitor patient adherence	Therapeutic range Kidney transplant (in combination with cyclosporine) – 4-12 ng/mL Toxic – >25 ng/mL
Tacrolimus by Tandem Mass Spectrometry 0090612	Optimize drug therapy and monitor patient adherence	Therapeutic range Kidney transplant 0-3 mos post transplant – 7-20 ng/mL ≥3 mos post transplant – 5-15 ng/mL Heart transplant 0-3 mos post transplant – 10-20 ng/mL ≥3 mos post transplant – 5-15 ng/mL Liver transplant 1-12 mos post transplant – 5-20 ng/mL Toxic – >25 ng/mL
Thiopurine Methyltransferase, RBC 0092066	Phenotype test to assess risk for severe myelosuppression with standard dosing of thiopurine drugs Use for individuals being considered for thiopurine therapy Must be performed before thiopurine therapy is initiated Can also detect rapid metabolizer phenotype.	Normal TPMT activity – 24-44 U/mL Low risk of bone marrow toxicity; no dose adjustment recommended Intermediate TPMT activity – 17-23.9 U/mL Intermediate risk of bone marrow toxicity; dose reduction and therapeutic drug management recommended Low TPMT activity – <17 U/mL High risk of bone marrow toxicity; avoid thiopurine drugs High TPMT activity – >44 U/mL No risk for bone marrow toxicity; may require higher than normal standard dose Therapeutic drug management recommended
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration TPMT, thiopurine methyltransferase

Monitoring

Therapeutic drug monitoring is required for patients on therapy

Therapeutic Drug Monitoring Recommendations for Organ Type
Drug	Kidney (KDOGO, 2010)	Liver (Lucey, AASLD/AST, 2013)	Heart (Costanzo, ISHLT, 2010)
Cyclosporine (CYA)	Monitor using 12-hr trough, or 2 hrs post dose, or Abbreviated AUC Measure blood levels every other day during immediate post operation until target reached, then with any change in patient status, kidney function, or medication	n/a	12-hr trough recommended over 2 hrs post dose
Tacrolimus	Monitor using 12-hr trough Measure blood levels every other day during immediate post operation until target reached, then with any change in patient status, kidney function, or medication	n/a	12-hr or 24-hr trough, depending on dosing schedule and type
Sirolimus	No recommendation provided	n/a	Measure trough concentration at least 5 days after dosage adjustment
Everolimus	Measure trough concentration at 4-5 days after initiation or dosage adjustment (van Gelder, 2017)	Measure trough concentration at 4-5 days after initiation or dosage adjustment (van Gelder, 2017)	Measure trough concentration at least 5 days (ISHLT, 2010) or 4-5 days (van Gelder, 2017) after initiation or dosage adjustment
Mycophenolic acid	Monitoring suggested (no schedule provided)	Need for therapeutic monitoring unclear	No recommendations for routine monitoring
n/a, not available Sources: AASLD/AST, American Association for the Study of Liver Diseases and the American Society of Transplantation; AUC, area under the curve; ISHLT, International Society of Heart and Lung Transplantation; KDIGO, Kidney Disease: Improving Global Outcomes

Kidney and liver function, other medications, anemia, and other changes in the patient’s condition may affect serum concentrations

Select known drugs and foods that affect immunosuppressive drug levels

Select Known Drugs and Foods that Affect Immunosuppressive Drug Levels
	Antimicrobials	Antifungals	Antiretroviral Therapy	Cardiovascular	Nutraceuticals	Others
Increase Levels	Clarithromycin Erythromycin Azithromycin Metronidazole and tinidazole Quinupristin/dalfopristin Levofloxacin Ofloxacin Ciprofloxacin	Clotrimazole Itraconazole Ketoconazole Fluconazole Posaconazole Voriconazole	Protease inhibitors (general) Amprenavir Atazanavir Darunavir Fosamprenavir Indinavir Nelfinavir Ritonavir Saquinavir Tipranavir	Amiodarone Diltiazem Verapamil	Bitter orange Grapefruit juice	Rilonacept Theophylline Cimetidine Fluvoxamine Glipizide Glyburide Imatinib Nefazodone Ganciclovir Valganciclovir
	Antiepileptics	Antimicrobials	Antiretroviral Therapy	Others
Decrease Levels	Carbamazepine Fosphenytoin Phenobarbital Phenytoin	Caspofungin Nafcillin Rifabutin Rifampin Rifapentine	Efavirenz Etravirine Nevirapine	Antacids containing magnesium, calcium, or aluminum (tacrolimus only) Deferasirox Modafinil St. John’s wort Thalidomide Ticlopidine Troglitazone
Sources: Adapted from Costanzo, International Society of Heart and Lung Transplantation (ISHLT), 2010; Lucey, American Association for the Study of Liver Diseases and the American Society of Transplantation (AASLD/AST), 2013

Pharmacogenetics

Thiopurine drugs
- Thiopurine prodrugs are metabolized via thiopurine methyltransferase (TPMT) enzymatic activity
- Deficiency of TPMT predicts hematopoietic toxicity after thiopurine treatment
- Testing to determine activity level may be helpful in dosing thiopurine drugs and averting bone marrow suppression
  - For deficient activity, dose reduction of 80-90% may be required
  - For intermediate activity, dose reduction of 20-50% may be required
- Genotype for TPMT cannot be inferred from TPMT activity (phenotype)
- TPMT phenotype testing does not replace need for clinical monitoring of patients treated with thiopurine drugs
  - Phenotype testing should not be requested for patients currently treated with thiopurine drugs; results will be falsely low
  - Current TPMT phenotype may not reflect future TPMT phenotype, particularly in patients who received blood transfusions within 30-60 days of testing

Background

Epidemiology

Incidence – ~33,600 organ transplants in U.S. in 2016 (U.S. Department of Health and Human Services, 2017)
Prevalence – >30,000 liver transplant 5-year survivors in the U.S. in 2011 (Lucey, 2013)
Survival rate 1 year post graft – 90%

Immunosuppressive Drug Regimens for Organ Transplants^a
Available Immunosuppressives^b	Mechanism of Action	Toxicity	Therapeutic Ranges
Alemtuzumab (Campath-IH, Lemtrada)	Lymphocyte-depleting antibody (targets CD52 on T cells, B cells, and NK cells, causing depletion)	Increases risk of infection	n/a
Antithymocyte globulin (Atgam)	Lymphocyte-depleting agent	Increases risk of infection	Aim for 0.1-0.3 lymphocytes/mL
Azathioprine (Imuran, Azasan) 6-mercaptopurine (Puinethol, Purixan)	Antiproliferative agent	Increases risk of infection and malignancy (acute myeloid leukemia and myelodysplastic syndromes)	n/a
Belatacept (Nulojix)	Binds to T cells to prevent CD28 signaling	Increases risk of infection	n/a
Corticosteroids	Proapoptotic effect on lymphoid cells; suppresses eicosanoid production; increases TGF expression	Increases risk of infection and malignancy (NMSC)	n/a
Cyclosporine A (Sandimmune, Neoral, Gengraf)	Calcineurin inhibitor	Increases risk of malignancy, nephrotoxicity, cardiotoxicity, hyperlipidemia Toxic level – >700 ng/mL	General therapeutic range – 100-400 ng/mL Kidney transplant (in combination with everolimus) 1 mo post transplant – 100-200 ng/mL 2-3 mos post transplant – 75-150 ng/mL 4-5 mos post transplant – 50-100 ng/mL 6-12 mos post transplant – 25-50 ng/mL Heart transplant Up to 3 mos post transplant – 350-525 ng/mL ≥4 months post transplant – 145-350 ng/mL Liver transplant 290-525 ng/mL
IL-2 antibodies Daclizumab (Zenapax) Basiliximab (Simulect)	IL-2 receptor antagonist (selectively blocks IL-2 receptors on T-helper cells, preventing T-cell proliferation)	Increases risk of malignancy (NMSC and lymphomas)	n/a
Muromonab-CD3 (Orthoclone OKT3)	Lymphocyte-depleting agent	Increases risk of infection	500-1,500 ng/mL during steady-state treatment
Mycophenolic acid (CellCept, Myfortic)	Antiproliferative agent (selectively inhibits inosine monophosphate dehydrogenase – interferes with DNA purine synthesis)	Increases risk of infection Toxic ranges are not well established, except for mycophenolic acid (>25 μg/mL)	Suggested therapeutic range (for 2 g/day dosing) Mycophenolic acid – 1.0-3.5 μg/mL 3 g/day dose may have up to 5.0 μg/mL concentration 2-4 μg/mL range is suggested for maximal efficacy with minimal toxicity Mycophenolic acid glucuronide – 35-100 μg/mL
Rituximab (Rituxan, MabThera)	B-cell-depleting agent (binds CD20 and B cells mediating lysis)	Increases risk of infection	n/a
Sirolimus (Rapamune) Everolimus (Zortress, Afinitor)	mTOR inhibitor	Increases risk of hyperlipidemia and infection Sirolimus toxic level – >25 ng/mL Everolimus toxic level – >15 ng/mL	Measured as trough level Sirolimus therapeutic ranges for kidney transplant (in combination with cyclosporine) 4-12 ng/mL Liver transplant 12-20 ng/mL (suggested range) Everolimus Kidney transplant (in combination with cyclosporine) – 3-8 ng/mL Liver transplant (in combination with tacrolimus) – 3-8 ng/mL
Tacrolimus (Prograf, Hecoria, Envarsus XR, Astagraf XL)	Calcineurin inhibitor	Increases risk of malignancy, nephrotoxicity, cardiotoxicity, hyperlipidemia Toxic level – ≥25 ng/mL	Measured as trough level Therapeutic ranges for kidney transplant 0-3 mos post transplant – 7.0-20.0 ng/mL ≥3 mos post transplant – 5.0-15.0 ng/mL Heart transplant 0-3 mos post transplant – 10.0-20.0 ng/mL ≥3 mos post transplant – 5.0-15.0 ng/mL Liver transplant 1-12 mos post transplant – 5-20 ng/mL
^aTrade names are in parentheses ^bImmunosuppressive regimen depends on organ transplanted n/a, not available; NMSC, nonmelanoma skin cancers; TGF, transforming growth factor

ARUP Lab Tests

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Cyclosporine A, 2-Hour Post Dose (C2) by Tandem Mass Spectrometry 0058902
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Optimize drug therapy and monitor patient adherence

Cyclosporine A by Tandem Mass Spectrometry 0070035
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Optimize drug therapy and monitor patient adherence

Limitations

Results from different methodologies (mass spectrometry versus immunoassay) cannot be used interchangeably

Generally, immunoassay methods have been reported to have a positive bias in results when compared to mass spectrometry due to antibody cross-reactivity

Everolimus by Tandem Mass Spectrometry 0092118
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Optimize drug therapy and monitor patient adherence

Trough concentrations should be assessed ~2 weeks after beginning treatment

Interferences from commonly used drugs and associated metabolites have not been observed

Limitations

Results from different methodologies (mass spectrometry versus immunoassay) cannot be used interchangeably

Generally, immunoassay methods have been reported to have a positive bias in results when compared to mass spectrometry due to antibody cross-reactivity

Mycophenolic Acid and Metabolites 2010359
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Optimize drug therapy and monitor patient adherence

Predose (trough) concentration at steady state should be assessed

Limitations

Toxic and therapeutic ranges are not well established for metabolites except for mycophenolic acid (>25 μg/mL)

Sirolimus by Tandem Mass Spectrometry 0098467
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Optimize drug therapy and monitor patient adherence

Limitations

Results from different methodologies (mass spectrometry versus immunoassay) cannot be used interchangeably

Generally, immunoassay methods have been reported to have a positive bias in results when compared to mass spectrometry due to antibody cross-reactivity

Tacrolimus by Tandem Mass Spectrometry 0090612
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Optimize drug therapy and monitor patient adherence

Limitations

Results from different methodologies (mass spectrometry versus immunoassay) cannot be used interchangeably

Generally, immunoassay methods have been reported to have a positive bias in results when compared to mass spectrometry due to antibody cross-reactivity

Thiopurine Methyltransferase, RBC 0092066
Method: Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use

Phenotype test to assess risk for severe myelosuppression with standard dosing of thiopurine drugs

Testing should be performed prior to initiation of thiopurine therapy

For therapy optimization or toxicity evaluation, order thiopurine metabolites by LC-MS/MS

Limitations

Does not replace clinical monitoring

Genotype cannot be inferred from thiopurine methyltransferase (TPMT) activity (phenotype)

TPMT inhibitors may contribute to falsely low test results

TPMT activity should be assessed prior to treatment with thiopurine drugs

Blood transfusion within 30 days may reflect donor status

Thiopurine Metabolites by LC-MS/MS 2014484
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Recommended Use

Phenotype test used to optimize therapy for patients who are taking thiopurine drugs

Thiopurine metabolite concentrations are identified to assess therapeutic and toxic concentrations

If thiopurine therapy has not been initiated, order thiopurine methyltransferase, red blood cell

Thiopurine Methyltransferase (TPMT) Genotyping, 4 Variants 2012233
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Recommended Use

Assess risk, due to genetics, for severe myelosuppression with standard dosing of thiopurine drugs

Use for individuals being considered for thiopurine therapy or who have had an adverse reaction to thiopurine therapy

Preferred test for patients with recent heterologous blood transfusion

Can be performed irrespective of thiopurine therapy

>20 TPMT deficiency alleles identified to date

TPMT deficiency alleles tested – *2 (c.238G>C; p.Ala80Pro), *3A (c.[460G>A;719A>G]; p.[Ala154Thr;Tyr240Cys]), *3B (c.460G>A; p.Ala154Thr), *3C (c.719A>G; p.Tyr240Cys)

Clinical sensitivity – 95%

Limitations

Only targeted TPMT allele variants will be detected by this panel

Diagnostic errors can occur due to rare sequence variations

Genotyping in patients who have received allogenic stem cell/bone marrow transplant will reflect donor status

Genotyping cannot distinguish the *1/*3A genotype from the *3B/*3C genotype

Thiopurine drug metabolism and risk for toxicity may be affected by genetic and nongenetic factors that are not evaluated by this test

Test does not assess for TPMT allele variants associated with ultra-high enzyme activity

Genotyping does not replace need for therapeutic drug monitoring or clinical observation

Lymphocyte Transplantation CD3 0095949
Method: Quantitative Flow Cytometry

Recommended Use

Monitor response to CD3 immunosuppressive therapy

Medical Reviewers

Johnson-Davis, Kamisha, PhD, DABCC, FAACC, Medical Director, Clinical Toxicology at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Lyon, Elaine, PhD, FACMG, Medical Director, Molecular Genetics and Genomics, Medical Director, Pharmacogenomics at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

McMillin, Gwendolyn A., PhD, Medical Director, Toxicology, and Medical Director, Pharmacogenetics, at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

Wittwer, Carl T., MD, PhD, Medical Director, Immunologic Flow Cytometry at ARUP Laboratories; Professor of Clinical Pathology, University of Utah

References

Guidelines

Kasiske BL, Zeier MG, Chapman JR, Craig JC, Ekberg H, Garvey CA, Green MD, Jha V, Josephson MA, Kiberd BA, Kreis HA, McDonald RA, Newmann JM, Obrador GT, Vincenti FG, Cheung M, Earley A, Raman G, Abariga S, Wagner M, Balk EM, Kidney Disease Improving Global Outcomes. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary Kidney Int. 2010; 77(4): 299-311. PubMed
Lucey MR, Terrault N, Ojo L, Hay E, Neuberger J, Blumberg E, Teperman LW. Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013; 19(1): 3-26. PubMed
Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, Fedson S, Fisher P, Gonzales-Stawinski G, Martinelli L, McGiffin D, Smith J, Taylor D, Meiser B, Webber S, Baran D, Carboni M, Dengler T, Feldman D, Frigerio M, Kfoury A, Kim D, Kobashigawa J, Shullo M, Stehlik J, Teuteberg J, Uber P, Zuckermann A, Hunt S, Burch M, Bhat G, Canter C, Chinnock R, Crespo-Leiro M, Delgado R, Dobbels F, Grady K, Kao W, Lamour J, Parry G, Patel J, Pini D, Towbin J, Wolfel G, Delgado D, Eisen H, Goldberg L, Hosenpud J, Johnson M, Keogh A, Lewis C, O'Connell J, Rogers J, Ross H, Russell S, Vanhaecke J, International Society of Heart and Lung Transplantation Guidelines. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010; 29(8): 914-56. PubMed

General References

Chadban S, Morris R, Hirsch HH, Bunnapradist S, Arns W, Budde K. Immunosuppression in renal transplantation: some aspects for the modern era. Transplant Rev (Orlando). 2008; 22(4): 241-51. PubMed

Geissler EK, Schlitt HJ. Immunosuppression for liver transplantation. Gut. 2009; 58(3): 452-63. PubMed

Rhee J, Al-Mana N, Freeman R. Immunosuppression in high-risk transplantation. Curr Opin Organ Transplant. 2009; 14(6): 636-42. PubMed

Rosen HR. Transplantation immunology: what the clinician needs to know for immunotherapy. Gastroenterology. 2008; 134(6): 1789-801. PubMed

Schonder KS, Mazariegos GV, Weber RJ. Adverse effects of immunosuppression in pediatric solid organ transplantation. Paediatr Drugs. 2010; 12(1): 35-49. PubMed

Srinivas TR, Meier-Kriesche H, Kaplan B. Pharmacokinetic principles of immunosuppressive drugs. Am J Transplant. 2005; 5(2): 207-17. PubMed

U.S. Dept of Health and Human Services, Organ Procurement and Transplantation Network. U.S. organ transplants and deceased donors set new records in 2016. Rockville, MD [Accessed: Aug 2017]

Urschel S, Altamirano-Diaz LA, West LJ. Immunosuppression armamentarium in 2010: mechanistic and clinical considerations. Pediatr Clin North Am. 2010; 57(2): 433-57, table of contents. PubMed

van Gelder T, Fischer L, Shihab F, Shipkova M. Optimizing everolimus exposure when combined with calcineurin inhibitors in solid organ transplantation. Transplant Rev (Orlando). 2017; 31(3): 151-157. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology^®

Barakauskas VE, Bradshaw TA, Smith LD, Lehman CM, Johnson-Davis KL. Process Optimization to Improve Immunosuppressant Drug Testing Turnaround Time. Am J Clin Pathol. 2016; 146(2): 182-90. PubMed

D.Merrigan S, Kish-Trier E, Seegmiller JC, Johnson-Davis KL. LC–MS/MS method for quantitation of mycophenolic acid, mycophenolic acid acyl-glucuronide, and 7-O-mycophenolic acid glucuronide in serum. Clinical Mass Spectrometry. 2017; 3: PubMed

Dasgupta A, Khalil SA, Johnson-Davis KL. Analytical Performance Evaluation of a New Cobas Tacrolimus Assay on Cobas e411 Analyzer: Comparison of Values Obtained by the CMIA Tacrolimus Assay and a Liquid Chromatography Combined with Tandem Mass Spectrometric Method. Ann Clin Lab Sci. 2016; 46(2): 204-8. PubMed

Gross TG, Orjuela MA, Perkins SL, Park JR, Lynch JC, Cairo MS, Smith LM, Hayashi RJ. Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a Children's Oncology Group Report. Am J Transplant. 2012; 12(11): 3069-75. PubMed

Johnson-Davis KL, Juenke JM, Thomas RL, Bradshaw T. Everolimus method comparison between Waters MassTrak™ Immunosuppressants XE (IUO) kit and an in-house laboratory developed LC-MS/MS method in renal transplant patients. Ann Clin Lab Sci. 2015; 45(1): 27-31. PubMed

McMillin GA, Johnson-Davis K, Dasgupta A. Analytical performance of a new liquid chromatography/tandem mass spectrometric method for determination of everolimus concentrations in whole blood. Ther Drug Monit. 2012; 34(2): 222-6. PubMed

Schniedewind B, Niederlechner S, Galinkin JL, Johnson-Davis KL, Christians U, Meyer EJ. Long-term cross-validation of everolimus therapeutic drug monitoring assays: the Zortracker study. Ther Drug Monit. 2015; 37(3): 296-303. PubMed

Scott JR, Courter JD, Saldaña SN, Widemann BC, Fisher M, Weiss B, Perentesis J, Vinks AA. Population pharmacokinetics of sirolimus in pediatric patients with neurofibromatosis type 1. Ther Drug Monit. 2013; 35(3): 332-7. PubMed

Ware AL, Malmberg E, Delgado JC, Hammond E, Miller DV, Stehlik J, Kfoury A, Revelo MP, Eckhauser A, Everitt MD. The use of circulating donor specific antibody to predict biopsy diagnosis of antibody-mediated rejection and to provide prognostic value after heart transplantation in children. J Heart Lung Transplant. 2016; 35(2): 179-85. PubMed

Wong SH, Johnson-Davis KL, Garrison K, Rankin JD, Muhammad CS. Everolimus TDM using Thermo Fisher QMS immunoassay on Indiko, Beckman DxC, AU680, and AU5800 analyzers. Clin Biochem. 2017; 50(7-8): 425-430. PubMed

Content Review:

August 2017

Last Update: September 2018


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Immunosuppressive Drug Optimization and Monitoring - Organ Transplantation Drugs

Diagnosis

Indications for Testing

Laboratory Testing

Monitoring

Pharmacogenetics

Background

Epidemiology

ARUP Lab Tests

Medical Reviewers

References

Guidelines

General References

References from the ARUP Institute for Clinical and Experimental Pathology®

References from the ARUP Institute for Clinical and Experimental Pathology^®