Therapeutic Drug Monitoring - TDM

Therapeutic drug monitoring (TDM) refers to the clinical practice of measuring drugs and/or metabolites in blood or serum/plasma at a specific time point to determine if a patient’s drug concentrations are within the therapeutic range, and are neither subtherapeutic nor potentially toxic. The purpose of TDM is to optimize dosing to target a therapeutic plasma drug concentration while minimizing toxicity.

Tabs Content

Clinical Overview

Quick Answers

What is the purpose of therapeutic drug monitoring (TDM)?

Effective drug treatment is dependent on patient adherence/compliance to prescribed medications. Drug treatment and dosage should be personalized for each patient due to interindividual variability in response to therapy. TDM allows for personalization of drug selection and dose, evaluation of adherence, and investigation of changes in pharmacokinetics (eg, drug-drug interactions).

When should TDM testing be performed?

Therapeutic drug monitoring should be performed once the patient has achieved steady-state concentration, and when there are changes to drug therapy and/or changes in response (eg, toxicity).

What specimens are appropriate for TDM?

Whole blood, serum, and plasma specimens can be used to assess if drug dosage avhieved the targeted therapeutic range and patient adherence. Urine specimens can be used to assess patient adherence to medication by detecting parent drug and metabolites.

How should results be interpreted?

Drug results should be interpreted relative to the established therapeutic range, dose-related range, or toxic range (if applicable), timing of specimen collection (eg, predose [trough], peak, or random), specimen type, and the patient’s clinical response to treatment. Results can be affected by several variables. Incorrect timing of specimen collection relative to the therapeutic range can be misleading. Response to drug therapy is also influenced by the patient’s pharmacogenetics (eg, normal, rapid, or poor drug metabolism), physical conditions (eg, pregnancy, comorbidities), and drug-drug or food-drug interactions that could lead to an increase, decrease, or inhibited response to therapy.

Indications for Testing

Not all medications require TDM, especially when the drug has a wide therapeutic index or low risk for severe adverse effects. TDM is utilized for drugs that have

Known relationship between dose and blood/serum/plasma concentrations
Narrow therapeutic window
High patient variability in pharmacokinetics (eg, drug liberation, absorption, distribution, metabolism, and elimination)
Severe adverse effects (dose related)

TDM is also used to

Identify drug-drug or food-drug interactions
Monitor patient compliance
Monitor status during decontamination or detoxification
Monitor changes in drug concentrations related to aging, pregnancy, or clinical status

TDM should be performed once a drug has reached steady state concentration.

Specimen Selection

Therapeutic and toxic ranges are typically established in the following specimen types: serum, plasma, and whole blood.

Serum/Plasma and Whole Blood

Clinical signs and symptoms of effective drug treatment, ineffective drug treatment, and toxicity may correlate with drug and/or metabolite concentrations in serum, plasma, and/or whole blood.

Serum, plasma, or whole blood specimens are also appropriate for

Patients on dialysis
Suspected cases of malabsorption (eg, gastric bypass)
Evaluating other aspects of an individual patient’s pharmacokinetics

Whole Blood

Whole blood specimens are used for TDM of select drugs such as immunosuppressive drugs (eg, cyclosporine A, tacrolimus, everolimus, sirolimus, and thiopurine drugs) due to drug accumulation in RBCs.

Oral Fluid (Saliva)

Oral fluid drug concentrations tend to correlate to serum/plasma concentrations. The window of drug detection is about 1-2 days after drug use; therefore, oral fluid can be used to detect recent drug exposure. Therapeutic ranges are not well established in oral fluid.

Urine

Urine drug and metabolite concentrations do not correlate with signs and symptoms of drug therapy or toxicity; therefore, urine should not be a specimen collected for TDM. Urine drug concentrations should also not be used to extrapolate the dose that was administered.

Timing of Specimen Collection

Therapeutic ranges are typically established at the following timed blood collections after steady state concentrations have been reached (generally 5-7 half-lives after initiation of or change in dosing).

Trough or predose (0-60 minutes before dose administration)
Peak (generally 1-2 hours after drug administration; however, this is highly drug dependent)
Randomly

Commonly Used Testing Strategy

Quantitative testing for TDM may be performed by immunoassay, high performance liquid chromatography (HPLC), or mass spectrometry. Drug results that are reported as less than the assay cutoff should be interpreted as “not detected.”

Drug Classes by Test, Indication, and Therapeutic Range/Toxic Level

Antibiotic Tests

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level
Antibiotic Level, Aztreonam 0060845	Monitor levels of antimicrobial drug, aztreonam	Normal peak serum concentration – 90-164 µg/mL with a 1 g IV dose 204-255 µg/mL with a 2 g IV dose Trough serum concentration – n/a
Antibiotic Level, Ceftazidime 2004886	Monitor levels of antimicrobial drug, ceftazidime	Normal peak serum concentration – 42 µg/mL with a 500 mg IV dose 69 µg/mL with a 1 g IV dose 159-186 µg/mL with a 2 g IV dose Trough serum concentration – n/a
Antibiotic Level, Meropenem 0060844	Monitor levels of antimicrobial drug, meropenem	Normal peak serum concentration – 26 µg/mL with a 500 mg IV dose 55-62 µg/mL with a 1 g IV dose Trough serum concentration – n/a
Antibiotic Level, Nafcillin 0060843	Monitor levels of antimicrobial drug, nafcillin	Normal peak serum concentration – 7.7 µg/mL with a 1 g PO dose 7.6 µg/mL with a 1 g IM dose 40 µg/mL with a 500 mg IV dose Trough serum concentration – n/a
Antibiotic Level, Piperacillin 0060842	Monitor levels of antimicrobial drug, piperacillin	Normal peak serum concentration – 389-484 µg/mL with a 4 g IV dose of piperacillin 209 µg/mL with a 3.375 g IV dose of piperacillin/tazobactam 224 µg/mL with a 4.5 g IV dose of piperacillin/tazobactam Trough serum concentration – n/a
Antibiotic Level, Ticarcillin 0060841	Monitor levels of antimicrobial drug, ticarcillin	Normal peak serum concentration – 324 µg/mL with a 3.1 g IV dose of ticarcillin/clavulanate Trough serum concentration – n/a
Gentamicin, Peak Level 0090305	Prevent adverse events such as ototoxicity by avoiding high drug concentrations	Optimal – 0.5-2.0 µg/mL Toxic – >2.0 µg/mL
Gentamicin, Trough Level 0090310	Optimize drug therapy and monitor patient adherence	Optimal – 0.5-2.0 µg/mL Toxic – >2.0 µg/mL
Sulfonamides (Sulfas) 0020044	Optimize drug therapy and monitor patient adherence	Therapeutic range – 5-15 mg/dL Toxic – >20 mg/dL
Vancomycin, Peak Level 0090325	Optimize drug therapy and monitor patient adherence; trough level testing recommended	Optimal – 30.0-40.0 µg/mL Toxic – ≥80.1 µg/mL
Vancomycin, Random Level 0090285	Optimize drug therapy and monitor patient adherence	Trough level optimal – 10.0-20.0 µg/mL Peak level optimal – 30.0-40.0 µg/mL
Vancomycin, Trough Level 0090330	Optimize drug therapy and monitor patient adherence Maximize drug efficacy by attaining target trough levels; recommended over peak or random levels	Optimal – 10.0-20.0 µg /mL
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Anticonvulsant/Antiepileptic Tests

(Note: Also refer to ARUP Consult’s Epilepsy topic)

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level
Carbamazepine Epoxide and Total 0092211	Optimize drug therapy and monitor patient adherence	Carbamazepine-10,11 Epoxide Therapeutic range – n/a Toxic – >15 µg/mL Total carbamazepine Therapeutic range – 4-12 µg/mL Toxic – >15 µg/mL
Carbamazepine, Free and Total, Serum or Plasma 2011763	Optimize drug therapy and monitor patient adherence	Total carbamazepine Therapeutic range – 4-12 µg/mL Toxic – >15 µg/mL Free carbamazepine Therapeutic range – 1-3 µg/mL Toxic – >3.8 µg/mL Percent free carbamazepine 8-35%
Carbamazepine, Total 0090260	Optimize drug therapy and monitor patient adherence	Total carbamazepine Therapeutic range – 4-12 µg/mL Toxic – >15 µg/mL
Clobazam Quantitative, Serum or Plasma 2008597	Optimize drug therapy and monitor patient adherence	n/a
Ethosuximide, Serum or Plasma 2010358	Optimize drug therapy and monitor patient adherence	Therapeutic range – 40-100 µg/mL Toxic – >150 µg/mL
Felbamate 0094030	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Toxic – >200 µg/mL
Gabapentin 0090057	Optimize drug therapy and monitor patient adherence	Therapeutic range – 2-20 µg/mL Toxic – n/a
Keppra (Levetiracetam) 0098627	Optimize drug therapy and monitor patient adherence	Therapeutic range – 12-46 µg/mL Toxic – n/a
Lacosamide, Serum or Plasma 2003182	Optimize drug therapy and monitor patient adherence	Therapeutic range – suggested range 5-10 µg/mL Dose-related range – 2.5-18 µg/mL Toxic – n/a
Lamotrigine 0090177	Optimize drug therapy and monitor patient adherence	Therapeutic range – 2.5-15 µg/mL Toxic – n/a
Methsuximide Metabolite, Serum or Plasma 3000251	Optimize drug therapy and monitor patient adherence	Normethsuximide – methsuximide metabolite Therapeutic range – 10-40 µg/mL
Oxcarbazepine or Eslicarbazepine Metabolite (MHD) 0098834	Optimize drug therapy and monitor patient adherence	Therapeutic range – 3-35 µg/mL Toxic – >40 µg/mL
Perampanel Quantitative, Serum or Plasma 2013025	Optimize drug therapy and monitor patient adherence	n/a
Phenobarbital 0090230	Optimize drug therapy and monitor patient adherence	0-2 months Therapeutic range – 15-30 µg/mL Toxic – ≥40.1 µg/mL 3 months and older Therapeutic range – 15-40 µg/mL Toxic – ≥50.1 µg/mL
Phenobarbital, Total/Free/Bound, Serum or Plasma 0091551	Optimize drug therapy and monitor patient adherence	n/a
Phenytoin, Free and Total 0090141	Preferred test for therapeutic drug management in patients with renal failure or conditions that may alter albumin concentrations	Phenytoin, Total Therapeutic range – 10-20 µg/mL Toxic – >30 µg/mL Phenytoin, Free Level Therapeutic – 1-2.5 µg/mL Toxic – >2.5 µg/mL Phenytoin, Percent Free 8-14%
Phenytoin, Free 2010481	Therapeutic drug management for patients with renal failure or conditions that may alter albumin concentrations	Therapeutic range – 1-2.5 µg/mL Toxic – >2.5 µg/mL
Phenytoin 0090090	Optimize drug therapy and monitor patient adherence This test can be ordered when fosphenytoin is administered	0-2 months Therapeutic – 6-14 µg/mL Toxic – ≥14.1 µg/mL 3 months and older Therapeutic – 10-20 µg/mL Toxic – ≥30.1 µg/mL
Pregabalin, Serum or Plasma 2011609	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Toxic – n/a
Primidone and Metabolite 0090202	Optimize drug therapy and monitor patient adherence; the active metabolite of primidone is phenobarbital	Phenobarbital 0-2 months Therapeutic range – 15-30 µg/mL Toxic – ≥40.1 µg/mL 3 months and older Therapeutic range – 15-40 µg/mL Toxic – ≥50.1 µg/mL Primidone (Mysoline) 5-12 µg/mL
Rufinamide, Serum or Plasma 2003176	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Dose-related range – 3-30 µg/mL Toxic – n/a
Tiagabine, Serum or Plasma 0091541	Optimize drug therapy and monitor patient adherence	n/a
Topiramate 0070390	Optimize drug therapy and monitor patient adherence	Therapeutic range – 5-20 µg/mL Toxic – n/a
Valproic Acid, Free and Total 0099310	Preferred test for therapeutic drug management in patients with renal failure or conditions that may alter albumin concentrations	Valproic Acid, Total Therapeutic range – 50-125 µg/mL Toxic – >150 µg/mL Valproic Acid, Free Therapeutic range – 7-23 µg/mL Toxic – >30 µg/mL Valproic Acid, Percent Free 5-18 percent
Valproic Acid 0090290	Optimize drug therapy and monitor patient adherence	Toxic – ≥151 µg/mL
Vigabatrin Quantitative, Serum or Plasma 2011039	Optimize drug therapy and monitor patient adherence	n/a
Zonisamide 0097908	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Toxic – >80 µg/mL
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Antidepressant Tests

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level
Tricyclic Antidepressants, Quantitative, Serum or Plasma 2007549	Optimize drug therapy and monitor patient adherence	Amitriptyline (Elavil, Vanatrip) Therapeutic range/toxic level – n/a Nortriptyline (Aventyl, Pamelor) Therapeutic range – 50-150 ng/mL Toxic – >500 ng/mL Total amitriptyline and nortriptyline Therapeutic range – 95-250 ng/mL Toxic – >500 ng/mL Imipramine (Tofranil) Therapeutic range/toxicity – n/a Desipramine (Norpramin) Therapeutic range – 100-300 ng/mL Toxic – >500 ng/mL Total imipramine and desipramine Therapeutic range – 150-300 ng/mL Toxic – >500 ng/mL Doxepin (Sinequan, Zonalon) Therapeutic range/toxicity – n/a Nordoxepin Therapeutic range/toxicity – n/a Total doxepin and nordoxepin Therapeutic range – 100-300 ng/mL Toxic – >500 ng/mL Protriptyline (Vivactil) Therapeutic range – 70-240 ng/mL Toxic – >400 ng/mL Clomipramine (Anafranil) Therapeutic range/toxicity – n/a Norclomipramine Therapeutic range/toxicity – n/a Total clomipramine and norclomipramine Therapeutic range – 220-500 ng/mL Toxic – >900 ng/mL
Amitriptyline and Nortriptyline, Serum or Plasma 0090158	Optimize drug therapy and monitor patient adherence	Therapeutic range (total) – 95-250 ng/mL Toxic – >500 ng/mL
Bupropion, Serum or Plasma 2010357	Optimize drug therapy and monitor patient adherence	Therapeutic range – 50-100 ng/mL Toxic – >400 ng/mL
Clomipramine and Metabolite, Serum or Plasma 0099336	Optimize drug therapy and monitor patient adherence	Therapeutic range (total) – 220-500 ng/mL Toxic – >900 ng/mL
Doxepin and Metabolite, Serum or Plasma 0090102	Optimize drug therapy and monitor patient adherence	Therapeutic range (total) – 100-300 ng/mL Toxic – >500 ng/mL
Fluoxetine and Metabolite Quantitative, Serum or Plasma 2014180	Optimize drug therapy and monitor patient adherence	Fluoxetine Dose-related range – 100-800 ng/mL Norfluoxetine Dose-related range – 100-600 ng/mL Fluoxetine and Norfluoxetine Toxic – >2000 ng/mL
Imipramine and Desipramine, Serum or Plasma 0090157	Optimize drug therapy and monitor patient adherence	Therapeutic range (total) – 150-300 ng/mL Toxic – >500 ng/mL
Nortriptyline 0090074	Optimize drug therapy and monitor patient adherence	Therapeutic range – 50-150 ng/mL Toxic – >500 ng/mL
Protriptyline, Serum or Plasma 0090106	Optimize drug therapy and monitor patient adherence	Therapeutic range – 70-240 ng/mL Toxic – >400 ng/mL
Sertraline 0098745	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Toxic – >300 ng/mL
Trazodone 0090316	Optimize drug therapy and monitor patient adherence	Therapeutic range – 0.5-2.5 µg/mL Toxic – >4 µg/mL
Venlafaxine and Metabolite, Serum or Plasma 2007957	Optimize drug therapy and monitor patient adherence	Therapeutic range (total) – 195-400 ng/mL Toxic – n/a
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Antifungal Tests

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level
Fluconazole, Quantitative by LC-MS/MS 0097621	Optimize drug therapy and monitor patient adherence	Therapeutic range – 5-20 µg/mL
Itraconazole, Quantitative by LC-MS/MS 0098519	Optimize drug therapy and monitor patient adherence	Therapeutic ranges Itraconazole (trough) – localized infection >0.5 µg/mL Itraconazole (trough) – systemic infection >1.0 µg/mL Hydroxyitraconazole – n/a
Posaconazole, Quantitative by LC-MS/MS 2001739	Optimize drug therapy and monitor patient adherence	Therapeutic range (trough) – >0.7 µg/mL
Voriconazole, Quantitation by LC-MS/MS 2001737	Optimize drug therapy and monitor patient adherence	Therapeutic range (trough) – 1-6 µg/mL Toxic – >6 µg/mL
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Antipsychotic Tests

(Note: Also refer to ARUP Consult’s Schizophrenia topic)

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level
Aripiprazole and Metabolite, Serum or Plasma 2007945	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Total (aripiprazole and dehydroaripiprazole) – 150-500 ng/mL Toxic – n/a
Chlorpromazine 0090870	Optimize drug therapy and monitor patient adherence	Therapeutic range Child (0-11 yrs) – 30-80 ng/mL Adult (≥12 yrs) – 50-300 ng/mL Toxic level Child (0-11 yrs) – >200 ng/mL Adult (≥12 yrs) – >750 ng/mL
Clozapine and Metabolites, Serum or Plasma, Quantitative 2013433	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Toxic – ≥1500 ng/mL
Fluphenazine 0099906	Optimize drug therapy and monitor patient adherence	Therapeutic range – 0.5-2 ng/mL Toxic – n/a
Haloperidol 0099640	Optimize drug therapy and monitor patient adherence	Therapeutic range – 5-20 ng/mL Toxic – >42 ng/mL
Lithium, Serum or Plasma 0020038	Monitor patient adherence and exposure	Therapeutic range – 0.5-1.5 mmol/L Toxic – 1.6 or greater mmol/L
Lurasidone Quantitative, Serum or Plasma 2013018	Optimize drug therapy and monitor patient adherence	n/a
Olanzapine 0098833	Optimize drug therapy and monitor patient adherence	Therapeutic range – 20-80 ng/mL Toxic – n/a
Paliperidone, Serum or Plasma 2007949	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Proposed dose-related range – 20-60 ng/mL Toxic – n/a
Perphenazine, Serum or Plasma 2011555	Optimize drug therapy and monitor patient adherence	Therapeutic range – 0.6-2.4 ng/mL Toxic – >12 ng/mL
Quetiapine, Serum or Plasma 2003118	Optimize drug therapy and monitor patient adherence	Predose draw (trough) – preferred Therapeutic range – 70-170 ng/mL Toxic – >1000 ng/mL Peak draw (1.5 hour post dose) – not recommended Therapeutic range – 100-1000 ng/mL Toxic – >1500 ng/mL
Risperidone and Metabolite, Serum or Plasma 2007951	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Total (risperidone and metabolite) – 20-60 ng/mL Toxic – n/a
Thiothixene, Serum or Plasma 2011783	Optimize drug therapy and monitor patient adherence	Therapeutic range – 1-15 ng/mL Toxic – n/a
Ziprasidone, Serum or Plasma 2007955	Optimize drug therapy and monitor patient adherence	Therapeutic range – n/a Proposed dose-related range – 50-200 ng/mL Toxic – n/a
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Cardiovascular Drug Tests

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level
Amiodarone and Metabolite 0090161	Optimize drug therapy and monitor patient adherence	Therapeutic range (total) – 0.5-2 µg/mL Toxic (total) – >3 µg/mL
Digitoxin 0090085	Optimize drug therapy and monitor patient adherence Does not measure digoxin (Lanoxin, Digitek); for digoxin testing, order digoxin test	Therapeutic range – 10-30 ng/mL Toxic – >45 ng/mL
Flecainide 0090003	Optimize drug therapy and monitor patient adherence	Therapeutic range – 0.20-1 µg/mL Toxic – >1.50 µg/mL
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Immunosuppressant Tests

(Note: Also refer to ARUP Consult’s Immunosuppressive Drug Optimization and Monitoring topic)

ARUP Test	Indications for Use	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 and older 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 – n/a
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 – n/a
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 and older – 5-15 ng/mL Heart transplant 0-3 mos post transplant – 10-20 ng/mL 3 mos and older – 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

Nonopioid Pain Medication Tests

(Note: Also refer to ARUP Consult’s Pain and Addiction Management topic)

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level
Acetaminophen 0090001	Aid in the assessment of acetaminophen toxicity	Critical values Post 4-hour ingestion – >150 µg/mL Post 12-hour ingestion – >40 µg/mL
Ibuprofen Quantitative, Serum or Plasma 2014183	Optimize drug therapy and monitor patient adherence	Therapeutic range – 10-50 µg/mL (may be seen with common dosages) Toxic – >200 µg/mL
Salicylate Assay 0090251	Aid in assessment of the etiology of anion gap acidosis	Analgesic – 2-10 mg/dL Anti-inflammatory – 10-30 mg/dL Toxic – ≥31 mg/dL or greater
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Oncology Tests

ARUP Test	Indications for Use	Therapeutic Range^a
Imatinib 3000539	Optimize dose, detect variable pharmacokinetics, and monitor patient adherence	Chronic myelogenous leukemia – >1000 ng/mL Gastrointestinal stromal tumor – >1100 ng/mL
Methotrexate, Sensitive 2005405	Monitor methotrexate concentration	Low dose – 0.50-1.00 µmol/L High dose/24 hrs – ≤5.00 µmol/L 48 hrs – ≤0.50 µmol/L 72 hrs – ≤0.10 µmol/L
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Opiate/Opioid Analgesic Tests

(Note: Also refer to ARUP Consult’s Pain and Addiction Management topic)

ARUP Test	Indications for Use	Therapeutic Range^a
Buprenorphine and Metabolites, Serum or Plasma, Quantitative 2012647	Monitor patient adherence	1 ng/mL
Fentanyl and Metabolite, Serum or Plasma, Quantitative 2011776	Monitor patient adherence	0.1 ng/mL
Methadone and Metabolite, Serum or Plasma, Quantitative 0090699	Monitor patient adherence	10 ng/mL
Opiates, Serum or Plasma, Quantitative 0092354	Monitor patient adherence	2 ng/mL for the following: Codeine Morphine 6-acetylmorphine Hydrocodone Hydromorphone xycodone Oxymorphone
Propoxyphene and Metabolite, Serum or Plasma, Quantitative 2010464	Monitor patient adherence	10 ng/mL
Tapentadol and Metabolite, Serum or Plasma, Quantitative 2003133	Monitor patient adherence	100 ng/mL for all except tapentadol (50 ng/mL)
Tramadol and Metabolite, Quantitative, Serum or Plasma 2014686	Monitor patient adherence	n/a
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Sedative-Hypnotics Tests

(eg, benzodiazepines, barbiturates, muscle relaxants)

ARUP Test	Indications for Use	Therapeutic Range^a/Toxic Level/Dose-Related Ranges
Alprazolam 0090010	Optimize drug therapy and monitor patient adherence	Dose-related ranges Anxiety – 10-40 ng/mL (dose – 1-4 mg/d) Phobia & panic – 50-100 ng/mL (dose – 6-9 mg/d) Toxic – >100 ng/mL
Barbiturates, Serum or Plasma, Quantitative 2012201	Optimize drug therapy and monitor patient adherence Useful for ruling out barbiturate exposure For follow-up testing of a presumptive result, urine barbiturates quantitative test is preferred	See individual drug analytes for therapeutic ranges and toxic thresholds
Benzodiazepines Detection 0090367	Screening test for benzodiazapines Results are unconfirmed and are to be used for medical (treatment) purposes only	n/a; qualitative only
Benzodiazepines, Serum or Plasma, Quantitative 2010445	Optimize drug therapy and monitor patient adherence	See individual drug analytes for therapeutic ranges and toxic thresholds
Carisoprodol and Meprobamate, Serum or Plasma, Quantitative 2011450	Optimize drug therapy and monitor patient adherence	Carisoprodol, Serum or Plasma Dose-related range – <8 µg/mL Toxic – ≥8 µg/mL Meprobamate, Serum or Plasma Dose-related range – 5-20 µg/mL Toxic – >40 µg/mL
Clonazepam 0090055	Optimize drug therapy and monitor patient adherence	Dose-related range – 20-70 ng/mL Dose (Adult) – 1-8 mg/d Toxic – >80 ng/mL
Clorazepate (Assayed as Nordiazepam) 0090196	Optimize drug therapy and monitor patient adherence	Dose-related range – 100-1500 ng/mL (based on common dosage amounts) Toxic – >2500 ng/mL
Diazepam and Nordiazepam 0090076	Optimize drug therapy and monitor patient adherence	Diazepam Dose-related range – 200-1000 ng/mL (based on normal dosage amounts) Nordiazepam Dose-related range – 100-1500 ng/mL (based on normal dosage amounts) Toxic – >2500 ng/mL
Ketamine and Metabolite Quantitative, Serum or Plasma 0091507	Monitor patient adherence and exposure	n/a
Librium and Nordiazepam 0090148	Optimize drug therapy and monitor patient adherence	Librium Therapeutic range – 500-3000 ng/mL Dose (adult) – 5-100 mg Toxic – >5000 ng/mL Nordiazepam Therapeutic range – 100-1500 ng/mL (based on normal dosages) Toxic – >2500 ng/mL
Lorazepam 0090181	Optimize drug therapy and monitor patient adherence	Dose-related range – 50-240 ng/mL Dose (adult) – 1-10 mg/d Toxic – >300 ng/mL
Prazepam (Assayed as Nordiazepam) 0090672	Optimize drug therapy and monitor patient adherence	Prazepam Dose-related range –20-60 mg/d Nordiazepam Dose-related range – 100-1500 ng/mL Toxic – >2500 ng/mL
Zolpidem, Serum or Plasma, Quantitative 2012652	Detect use, optimize dose, and/or monitor patient adherence	n/a
^aThe therapeutic range is based on serum predose (trough) draw at steady-state concentration

Frequently Asked Questions

What is the definition of half-life?

The half-life of a drug refers to the time it takes for 50% of the drug to be eliminated from blood.

What is the definition of steady-state concentration?

Steady-state concentration occurs when the rate of drug administration is equal to the rate of elimination. Generally, steady-state concentration can be achieved after patient has consistently administered the drug for the duration of 5-7 half-lives (eg, if a drug has a half-life of 24 hours and is administered once a day, then steady-state concentration can be achieved after 5-7 days of drug administration).

What is the window of detection of drugs in blood, serum, or plasma specimens?

In general, the window of detection in blood, serum, and plasma is 1-2 days after drug administration.

The window of detection for drugs is dependent on several factors, including the following

Half-life of the drug
Drug dose
Frequency of drug administration
Route of administration
Drug formulation
Chemistry of the drug (eg, water soluble vs lipid soluble, stability)
Patient’s age
Patient’s body composition and sex
Patient’s pathophysiology and pharmacokinetics
Coadministration of other medications
Hydration and nutrition status
Analytical limitations of testing

Can gel separator tubes be used for toxicology testing?

Gel separator tubes are not recommended for testing in toxicology. Drugs that are lipid soluble may be absorbed into the gel and may cause a falsely low drug result.

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.

Antibiotic Drug Tests

Antibiotic Level, Aztreonam 0060845
Method: Quantitative Bioassay

Antibiotic Level, Ceftazidime 2004886
Method: Bioassay

Antibiotic Level, Meropenem 0060844
Method: Quantitative Bioassay

Antibiotic Level, Nafcillin 0060843
Method: Quantitative Bioassay

Antibiotic Level, Piperacillin 0060842
Method: Quantitative Bioassay

Antibiotic Level, Ticarcillin 0060841
Method: Quantitative Bioassay

Gentamicin, Peak Level 0090305
Method: Immunoassay

Gentamicin, Trough Level 0090310
Method: Immunoassay

Sulfonamides (Sulfas) 0020044
Method: Quantitative Colorimetry

Vancomycin, Peak Level 0090325
Method: Immunoassay

Vancomycin, Random Level 0090285
Method: Fluorescence Polarization Immunoassay

Vancomycin, Trough Level 0090330
Method: Immunoassay

Anticonvulsant/Antiepileptic Drug Tests

Carbamazepine Epoxide and Total 0092211
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry/Quantitative Enzyme Multiplied Immunoassay Technique

Carbamazepine, Free and Total, Serum or Plasma 2011763
Method: Quantitative Enzyme Multiplied Immunoassay Technique

Carbamazepine, Total 0090260
Method: Immunoassay

Clobazam Quantitative, Serum or Plasma 2008597
Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Ethosuximide, Serum or Plasma 2010358
Method: Quantitative Enzyme Immunoassay

Felbamate 0094030
Method: Quantitative High Performance Liquid Chromatography

Gabapentin 0090057
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Keppra (Levetiracetam) 0098627
Method: Quantitative Enzyme Immunoassay

Lacosamide, Serum or Plasma 2003182
Method: High Performance Liquid Chromatography/Tandem Mass Spectrometry

Lamotrigine 0090177
Method: Quantitative Enzyme Immunoassay

Methsuximide Metabolite, Serum or Plasma 3000251
Method: Quantitative High Performance Liquid Chromatography

Oxcarbazepine or Eslicarbazepine Metabolite (MHD) 0098834
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Perampanel Quantitative, Serum or Plasma 2013025
Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Phenobarbital 0090230
Method: Immunoassay

Phenobarbital, Total/Free/Bound, Serum or Plasma 0091551
Method: Quantitative High Performance Liquid Chromatography

Phenytoin, Free and Total 0090141
Method: Quantitative Enzyme Multiplied Immunoassay Technique

Phenytoin, Free 2010481
Method: Quantitative Enzyme Multiplied Immunoassay Technique

Phenytoin 0090090
Method: Enzyme Immunoassay

Pregabalin, Serum or Plasma 2011609
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Primidone and Metabolite 0090202
Method: Immunoassay

Rufinamide, Serum or Plasma 2003176
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Tiagabine, Serum or Plasma 0091541
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Topiramate 0070390
Method: Quantitative Enzyme Immunoassay

Valproic Acid, Free and Total 0099310
Method: Quantitative Enzyme Multiplied Immunoassay Technique

Valproic Acid 0090290
Method: Fluorescence Polarization Immunoassay

Vigabatrin Quantitative, Serum or Plasma 2011039
Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Zonisamide 0097908
Method: Quantitative Enzyme Multiplied Immunoassay Technique

Antidepressant Drug Tests

Amitriptyline and Nortriptyline, Serum or Plasma 0090158
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Bupropion, Serum or Plasma 2010357
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Clomipramine and Metabolite, Serum or Plasma 0099336
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Doxepin and Metabolite, Serum or Plasma 0090102
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Fluoxetine and Metabolite Quantitative, Serum or Plasma 2014180
Method: Quantitative Gas Chromatography/Mass Spectrometry (GC/MS)

Imipramine and Desipramine, Serum or Plasma 0090157
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Nortriptyline 0090074
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Protriptyline, Serum or Plasma 0090106
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Sertraline 0098745
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Trazodone 0090316
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Tricyclic Antidepressants, Quantitative, Serum or Plasma 2007549
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Venlafaxine and Metabolite, Serum or Plasma 2007957
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Antifungal Drug Tests

Fluconazole, Quantitative by LC-MS/MS 0097621
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Itraconazole, Quantitative by LC-MS/MS 0098519
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Posaconazole, Quantitative by LC-MS/MS 2001739
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Voriconazole, Quantitation by LC-MS/MS 2001737
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Antipsychotic Drug Tests

Aripiprazole and Metabolite, Serum or Plasma 2007945
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Chlorpromazine 0090870
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Clozapine and Metabolites, Serum or Plasma, Quantitative 2013433
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Fluphenazine 0099906
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Haloperidol 0099640
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Lithium, Serum or Plasma 0020038
Method: Colorimetry

Lurasidone Quantitative, Serum or Plasma 2013018
Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Olanzapine 0098833
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Paliperidone, Serum or Plasma 2007949
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Perphenazine, Serum or Plasma 2011555
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Quetiapine, Serum or Plasma 2003118
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Risperidone and Metabolite, Serum or Plasma 2007951
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Thiothixene, Serum or Plasma 2011783
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Ziprasidone, Serum or Plasma 2007955
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Cardiovascular Drug Tests

Amiodarone and Metabolite 0090161
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Digitoxin 0090085
Method: Quantitative CEDIA Immunoassay

Flecainide 0090003
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Immunosuppressant Drug Tests

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

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

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

Leflunomide Metabolite, Serum or Plasma 2007460
Method: High Performance Liquid Chromatography/Mass Spectrometry

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

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

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

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

Nonopioid Pain Medication Drug Tests

Acetaminophen 0090001
Method: Spectrophotometry

Salicylate Assay 0090251
Method: Spectrophotometry

Ibuprofen Quantitative, Serum or Plasma 2014183
Method: Quantitative High Performance Liquid Chromatography

Oncology Tests

Imatinib 3000539
Method: Immunoturbidimetry

Methotrexate, Sensitive 2005405
Method: Quantitative Immunoassay

Opiate/Opioid Analgesic Drug Tests

Buprenorphine and Metabolites, Serum or Plasma, Quantitative 2012647
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Fentanyl and Metabolite, Serum or Plasma, Quantitative 2011776
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry

Methadone and Metabolite, Serum or Plasma, Quantitative 0090699
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Opiates, Serum or Plasma, Quantitative 0092354
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Propoxyphene and Metabolite, Serum or Plasma, Quantitative 2010464
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Tapentadol and Metabolite, Serum or Plasma, Quantitative 2003133
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Tramadol and Metabolite, Quantitative, Serum or Plasma 2014686
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Sedative-hypnotics Drug Tests

Alprazolam 0090010
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Barbiturates, Serum or Plasma, Quantitative 2012201
Method: Quantitative Gas Chromatography-Mass Spectrometry

Benzodiazepines Detection 0090367
Method: Immunoassay

Benzodiazepines, Serum or Plasma, Quantitative 2010445
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Carisoprodol and Meprobamate, Serum or Plasma, Quantitative 2011450
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Clonazepam 0090055
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Clorazepate (Assayed as Nordiazepam) 0090196
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Diazepam and Nordiazepam 0090076
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Ketamine and Metabolite Quantitative, Serum or Plasma 0091507
Method: Quantitative Gas Chromatography-Mass Spectrometry

Librium and Nordiazepam 0090148
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Lorazepam 0090181
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Prazepam (Assayed as Nordiazepam) 0090672
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Zolpidem, Serum or Plasma, Quantitative 2012652
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Medical Reviewers

Johnson-Davis, Kamisha, PhD, DABCC, FAACC, Medical Director, Clinical Toxicology at ARUP Laboratories; Assistant 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

References

General References

Moller M, Gareri J, Koren G. A review of substance abuse monitoring in a social services context: a primer for child protection workers. Can J Clin Pharmacol. 2010; 17(1): e177-93. PubMed

Moyer T, McMillin G. Therapeutic Drugs. In Burtis CA, Ashwood ER and Burns DE. Tietz Fundamentals of Clinical Chemistry, 6th ed. MO: Saunders/Elsevier, 2008.

Moyer T, Shaw L. Therapeutic drugs and their management. In Burtis CA, Ashwood ER and Burns DE. Clinical Chemistry & Molecular Diagnositcs, 4th ed. Philadelphia: WB Saunders, 2005.

Passik SD. Issues in long-term opioid therapy: unmet needs, risks, and solutions. Mayo Clin Proc. 2009; 84(7): 593-601. PubMed

Riedel M, Musil R, Seemüller F, Spellmann I, Möller H, Schennach-Wolff R. Safety evaluation of zotepine for the treatment of schizophrenia. Expert Opin Drug Saf. 2010; 9(4): 659-66. PubMed

Schultz SH, North SW, Shields CG. Schizophrenia: a review. Am Fam Physician. 2007; 75(12): 1821-9. PubMed

Shin JK, Malone DT, Crosby IT, Capuano B. Schizophrenia: a systematic review of the disease state, current therapeutics and their molecular mechanisms of action. Curr Med Chem. 2011; 18(9): 1380-404. PubMed

Content Review:

January 2018

Last Update: June 2018


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Therapeutic Drug Monitoring - TDM

Quick Answers

What is the purpose of therapeutic drug monitoring (TDM)?

When should TDM testing be performed?

What specimens are appropriate for TDM?

How should results be interpreted?

Indications for Testing

Specimen Selection

Serum/Plasma and Whole Blood

Whole Blood

Oral Fluid (Saliva)

Urine

Timing of Specimen Collection

Commonly Used Testing Strategy

Drug Classes by Test, Indication, and Therapeutic Range/Toxic Level

Antibiotic Tests

Anticonvulsant/Antiepileptic Tests

Antidepressant Tests

Antifungal Tests

Antipsychotic Tests

Cardiovascular Drug Tests

Immunosuppressant Tests

Nonopioid Pain Medication Tests

Oncology Tests

Opiate/Opioid Analgesic Tests

Sedative-Hypnotics Tests

Frequently Asked Questions

ARUP Lab Tests

Antibiotic Drug Tests

Anticonvulsant/Antiepileptic Drug Tests

Antidepressant Drug Tests

Antifungal Drug Tests

Antipsychotic Drug Tests

Cardiovascular Drug Tests

Immunosuppressant Drug Tests

Nonopioid Pain Medication Drug Tests

Oncology Tests

Opiate/Opioid Analgesic Drug Tests

Sedative-hypnotics Drug Tests

Medical Reviewers

References

General References