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Therapeutic Drug Monitoring - TDM. ARUP Consult©. Retrieved April 09, 2020, https://arupconsult.com/content/therapeutic-drug-monitoring

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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.

Quick Answers for Clinicians

What is the purpose of therapeutic drug monitoring?

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. Therapeutic drug monitoring allows for personalization of drug selection and dose, evaluation of adherence, and investigation of changes in pharmacokinetics (eg, drug-drug interactions).

When should therapeutic drug monitoring be performed?

Therapeutic drug monitoring should be performed once the patient has achieved steady-state concentration, has changed drug therapy, or has had a change in response to treatment (eg, toxicity).

Which specimens are appropriate for therapeutic drug monitoring?

Whole blood, serum, and plasma specimens can be used to assess if drug dosage achieved the targeted therapeutic range and patient adherence. Urine drug and metabolite concentrations do not correlate with signs and symptoms of drug therapy or toxicity and should not be used for therapeutic drug monitoring (TDM).

How should therapeutic drug monitoring results be interpreted?

Test 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 with a

  • 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)
  • Potential for severe adverse effects (dose related)

TDM is also used to identify drug-drug or food-drug interactions and 

  • 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 for serum, plasma, and whole blood specimens. Urine should not be utilized for TDM.

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 red blood cells (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.”

Frequently Asked Questions

ARUP Lab Tests

Antiarrhythmic Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Therapeutic range: 0.5-2 µg/mL

Toxic level: >3 µg/mL

Therapeutic range: 10-30 ng/mL

Toxic level: >45 ng/mL

Therapeutic range: 0.8-2 ng/mL

Toxic level: >2.4 ng/mL

Therapeutic range: 0.2-1 µg/mL

Toxic level: >1.5 µg/mL

Therapeutic range: 0.5-2 µg/mL

Toxic level: >2 µg/mL

Commonly expected therapeutic range for the sum of NAPA and procainamide: 5-30 µg/mL

The concentration of NAPA is dependent on many factors, including time of last procainamide dose, mode of administration, concomitant drug therapy, sample condition, time of sample collection, and individual variations in absorption, biotransformation, distribution, and excretion

Therapeutic range: 1.5-4.5 µg/mL

Toxic level: ≥5.9 µg/mL

Antibiotic Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Note that therapeutic ranges depend on pathogen being treated.

Optimize drug therapy and monitor patient adherence

Trough levels

  • Optimal range: 4-8 µg/mL
  • Toxic level: ≥8.1 µg/mL

Peak levels

  • Optimal range: 20-30 µg/mL
  • Toxic level: ≥30.1 µg/mL

Optimal range: 4-8 µg/mL

Toxic level: ≥8.1 µg/mL

Normal peak serum concentration:

  • 90-164 µg/mL with a 1 g IV dose
  • 204-255 µg/mL with a 2 g IV dose

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

Normal peak serum concentration: 

  • 26 µg/mL with a 500 mg IV dose
  • 55-62 µg/mL with a 1 g IV dose

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

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

Normal peak serum concentration: 324 µg/mL with a 3.1 g IV dose of ticarcillin/clavulanate

Peak serum concentration: 0.2-0.7 µg/mL approximately 2-3 weeks post 250-500 mg dose of oral azithromycin

Target range for conventional treatment of mycobacterial infections: 35-45 µg/mL approximately 1 hr after intramuscular injection or 1 hr after the end of IV infusion

Target range for high dose, three times weekly treatment of mycobacterial infection: 65-80 µg/mL approximately 1 hr after intramuscular injection or 1 hr after the end of IV infusion

Usual tuberculostatic (chronic) level: 2-5 µg/mL at 4 hrs after last dose

Toxic level: >10 µg/mL

Optimal range: 5-10 µg/mL

Toxic level: <12 µg/mL

Optimal range: 0.5-2 µg/mL

Toxic level: >2 µg/mL

Optimal range: 30-40 µg/mL

Pathogens when MIC ≤1: 15 µg/mL

Complicated infections: 15-20 µg/mL

Toxic level: ≥80.1 µg/mL

Trough level (optimal): 10-20 µg/mL

Peak level (optimal): 30-40 µg/mL

Optimal level: 10-20 µg /mL

Antibody Therapeutic Tests

Evaluate response failure to adalimumab therapy

Determine and adjust dosage or identify the need for change to another anti-TNF-α inhibitor

Adalimumab activity and adalimumab neutralizing antibody titer not detected: higher dose of adalimumab or shortening dosing interval may be appropriate

Adalimumab activity not detected and adalimumab neutralizing antibody titer ≥1:20: change to another anti-TNF-α drug may be appropriate

Adalimumab activity ≥0.65 µg/mL and adalimumab neutralizing antibody titer not detected: change to another type of therapy (not targeting TNF-α) may be appropriate

Adalimumab activity ≥0.65 µg/mL and adalimumab neutralizing antibody titer ≥1:20: repeat testing is suggested to rule out decreasing adalimumab activity and/or increasing adalimumab neutralizing antibodies

Adalimumab activity and adalimumab neutralizing antibody titer not detected: higher dose of adalimumab or shortening dosing interval may be appropriate

Adalimumab activity not detected and adalimumab neutralizing antibody titer ≥1:20: change to another anti-TNF-α drug may be appropriate

Adalimumab activity ≥0.65 µg/mL and adalimumab neutralizing antibody titer not detected: change to another type of therapy (not targeting TNF-α) may be appropriate

Adalimumab activity ≥0.65 µg/mL and adalimumab neutralizing antibody titer ≥1:20: repeat testing is suggested to rule out decreasing adalimumab activity and/or increasing adalimumab neutralizing antibodies

Evaluate response failure to infliximab or biosimilar therapy

Determine and adjust dosage or identify the need for change to another anti-TNF-α inhibitor

Infliximab activity and infliximab neutralizing antibody titer not detected: higher dose of infliximab or shortening dosing interval may be appropriate

Infliximab activity not detected and infliximab neutralizing antibody titer ≥1:20: change to another anti-TNF-α drug may be appropriate

Infliximab activity ≥0.65 µg/mL and infliximab neutralizing antibody titer not detected: change to another type of therapy (not targeting TNF-α) may be appropriate

Infliximab activity ≥0.65 µg/mL and infliximab neutralizing antibody titer ≥1:20: repeat testing is suggested to rule out decreasing infliximab activity and/or increasing infliximab neutralizing antibodies

Infliximab activity and infliximab neutralizing antibody titer not detected: higher dose of infliximab or shortening dosing interval may be appropriate

Infliximab activity not detected and infliximab neutralizing antibody titer ≥1:20: change to another anti-TNF-α drug may be appropriate

Infliximab activity ≥0.65 µg/mL and infliximab neutralizing antibody titer n/a: change to another type of therapy (not targeting TNF-α) may be appropriate

Aid in management of individuals receiving natalizumab therapy

Anticoagulant Tests

Monitor treatment efficacy of low molecular weight heparin

Therapeutic range based on enoxaparin brand low molecular weight heparin

Monitor warfarin treatment

Anticonvulsant/Antiepileptic Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Carbamazepine-10,11 Epoxide

  • Therapeutic range: 0.4-4 µg/mL
  • Toxic level: >15 µg/mL

Total carbamazepine

  • Therapeutic range: 4-12 µg/mL
  • Toxic level: >15 µg/mL

Total carbamazepine

  • Therapeutic range: 4-12 µg/mL
  • Toxic level: >15 µg/mL

Free carbamazepine

  • Therapeutic range: 1-3 µg/mL
  • Toxic level: >3.8 µg/mL

Percent free carbamazepine: 8-35%

Therapeutic range: 4-12 µg/mL

Toxic level: >15 µg/mL

Therapeutic range (clobazam): 30-300 ng/mL

Therapeutic range (norclobazam): 300-3,000 ng/mL

Therapeutic range: 40-100 µg/mL

Toxic level: >150 µg/mL

Therapeutic range: 30-60 μg/mL

Toxic level: >120 µg/mL

Therapeutic range: 2-20 µg/mL

Toxic level: not well established

Therapeutic range: 12-46 µg/mL

Toxic level: not well established

Therapeutic range: suggested range 5-10 µg/mL

Dose-related range: 2.5-18 µg/mL

Toxic level: not well established

Therapeutic range: 2.5-15 µg/mL

Toxic level: not well established

Therapeutic range: 3-35 µg/mL

Toxic level: >40 µg/mL

Peak plasma concentration: ~460 ng/mL with daily administration of 6 mg at approximately 1.3 hrs post dose

Peak plasma concentration: ~800 ng/mL with single 12 mg dose

0-2 mos:

  • Therapeutic range: 15-30 µg/mL
  • Toxic level: ≥40.1 µg/mL

3 mos and older:

  • Therapeutic range: 15-40 µg/mL
  • Toxic level: ≥50.1 µg/mL

Dose-related range: 2-10 µg/mL

Toxic level: not well established

Therapeutic range: 3-30 µg/mL

Dose-related range: 3-30 µg/mL

Toxic level: not well established

Therapeutic range: 20-200 ng/mL

Toxic level: >300 ng/mL

Therapeutic range:  5-20 µg/mL

Toxic level: not well established

Toxic level: ≥151 µg/mL

Therapeutic range: 2-10 μg/mL

Toxic level: >20 μg/mL

Therapeutic range: not well established

Toxic level: >80 µg/mL

Preferred test for therapeutic drug management in patients with renal failure or conditions that may alter albumin concentrations

Total phenytoin

  • Therapeutic range: 10-20 µg/mL
  • Toxic level: >30 µg/mL

Free phenytoin

  • Therapeutic: 1-2.5 µg/mL
  • Toxic level: >2.5 µg/mL

Percent free phenytoin: 8-14%

Total valproic acid:

  • Therapeutic range: 50-125 µg/mL
  • Toxic level: >150 µg/mL

Free valproic acid:

  • Therapeutic range: 7-23 µg/mL
  • Toxic level: >30 µg/mL

Percent free valproic acid: 5-18%

Therapeutic drug management for patients with renal failure or conditions that may alter albumin concentrations

Therapeutic range:  1-2.5 µg/mL

Toxic level: >2.5 µg/mL

Optimize drug therapy and monitor patient adherence

This test can be ordered when fosphenytoin is administered

0-2 mos:

  • Therapeutic range: 6-14 µg/mL
  • Toxic level: ≥14.1 µg/mL

3 mos and older:

  • Therapeutic range: 10-20 µg/mL
  • Toxic level: ≥30.1 µg/mL

Optimize drug therapy and monitor patient adherence

The active metabolite of primidone is phenobarbital

Phenobarbital
0-2 mos:

  • Therapeutic range: 15-30 µg/mL
  • Toxic level: ≥40.1 µg/mL

3 mos and older:

  • Therapeutic range: 15-40 µg/mL
  • Toxic level: ≥50.1 µg/mL

Primidone (Mysoline)
Reference interval: 5-12 µg/mL

Antidepressant Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Drugs tested, therapeutic ranges/toxic levels:

  • Amitriptyline (Elavil, Vanatrip): therapeutic range/toxic level not established
  • Amoxapine
  • Clomipramine (Anafranil): therapeutic range/toxic level not established
  • Desipramine (Norpramin): therapeutic range, 100-300 ng/mL; toxic level, >500 ng/mL
  • Desmethylclomipramine
  • Desmethyldoxepin
  • Desmethyltrimipramine
  • Doxepin (Sinequan, Zonalon): therapeutic range/toxic level not established
  • Fluoxetine
  • Imipramine (Tofranil): therapeutic range/toxic level not established
  • Maprotiline
  • Mirtazapine
  • Norfluoxetine
  • Nortriptyline (Aventyl, Pamelor): therapeutic range, 50-150 ng/mL; toxic level, >500 ng/mL
  • Protriptyline (Vivactil): therapeutic range, 70-240 ng/mL; toxic level, >400 ng/mL
  • Trazadone
  • Trimipramine

Drugs tested, therapeutic ranges/toxic levels:

  • Amitriptyline (Elavil, Vanatrip): therapeutic range/toxic level not established
  • Nortriptyline (Aventyl, Pamelor): therapeutic range, 50-150 ng/mL; toxic level, >500 ng/mL
  • Total amitriptyline and nortriptyline: therapeutic range, 95-250 ng/mL; toxic level, >500 ng/mL
  • Imipramine (Tofranil): therapeutic range/toxic level not established
  • Desipramine (Norpramin): therapeutic range, 100-300 ng/mL; toxic level, >500 ng/mL
  • Total imipramine and desipramine: therapeutic range, 150-300 ng/mL; toxic level, >500 ng/mL
  • Doxepin (Sinequan, Zonalon): therapeutic range/toxic level not established
  • Nordoxepin: therapeutic range/toxic level not established
  • Total doxepin and nordoxepin: therapeutic range, 100-300 ng/mL; toxic level, >500 ng/mL
  • Protriptyline (Vivactil): therapeutic range, 70-240 ng/mL; toxic level, >400 ng/mL
  • Clomipramine (Anafranil): therapeutic range/toxic level not established
  • Norclomipramine: therapeutic range/toxic level not established
  • Total clomipramine and norclomipramine: therapeutic range, 220-500 ng/mL; toxic level, >900 ng/mL

Therapeutic range (total): 95-250 ng/mL

Toxic level: >500 ng/mL

Therapeutic range: 50-100 ng/mL

Toxic level: >400 ng/mL

Therapeutic range: 50-110 ng/mL

Toxic level: >220 ng/mL

Therapeutic range (total): 220-500 ng/mL

Toxic level: >900 ng/mL

Therapeutic range: 100-300 ng/mL

Toxic level: >500 ng/mL

Therapeutic range (total): 100-300 ng/mL

Toxic level: >500 ng/mL

Therapeutic range: 15-80 ng/mL

Toxic level: >160 ng/mL

Therapeutic range: 60-230 ng/mL

Toxic level: >500 ng/mL

Therapeutic range: 120-500 ng/mL

Toxic level: >1,000 ng/mL

Therapeutic range (total): 150-300 ng/mL

Toxic level: >500 ng/mL

Therapeutic range: 50-150 ng/mL

Toxic level: >500 ng/mL

Therapeutic range: 70-240 ng/mL

Toxic level: >400 ng/mL

Toxic level: >300 ng/mL

Therapeutic range: 0.5-2.5 µg/mL

Toxic level: >4 µg/mL

Therapeutic range (total): 195-400 ng/mL

Toxic level: not well established

Antidiabetic Tests

Preferred test when determining if hypoglycemia is from exposure to metformin

Serum or plasma is the preferred specimen for correlating drug use with hypoglycemia

Therapeutic range: 1-2 µg/mL

Metformin-related lactic acidosis generally associated with plasma concentrations >5 µg/mL

Preferred test for evaluating if etiology of hypoglycemia is sulfonylurea ingestion

Antifungal Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Normal peak serum concentration for 5-fluorocytosine: 30-45 µg/mL with a 2 g PO dose or 60-80 µg/mL with a 100 mg/kg/day PO dose

Trough serum concentration: not well established

Toxicity may be seen with sustained levels greater than 100 µg/mL.

Therapeutic range: 5-20 µg/mL

Toxic level: not well established

Therapeutic ranges:

  • Itraconazole, localized infection: >0.5 µg/mL
  • Itraconazole, systemic infection: >1.0 µg/mL
  • Hydroxyitraconazole: no therapeutic range established

Toxic level: not well established

Therapeutic range: >0.7 µg/mL

Toxic level: not well established

Therapeutic range: 1-5.5 µg/mL

Toxic level: >6 µg/mL

Antihypertensive Tests

Monitor treatment efficacy

Therapeutic range: 1-2 ng/mL

Toxic level: not well established

Peak plasma concentration: 20-340 ng/mL following oral administration of multiple doses of metoprolol tartrate (50-80 mg 3 times daily)

Antipsychotic Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize drug therapy and monitor patient adherence

Therapeutic range (suggested): 150-500 ng/mL

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

Therapeutic range: not well established

Toxic level: ≥1,500 ng/mL

Therapeutic range: 0.5-2 ng/mL

Toxic level: not well established

Therapeutic range: 5-20 ng/mL

Toxic level: >42 ng/mL

Mean Cmax values in serum:

Following single dose administration of 40 mg: 54 ng/mL

Following single dose administration of 80 mg: 64 ng/mL

Following steady-state administration of 40 mg: 48 ng/mL

Following steady-state administration of 80 mg: 79 ng/mL 

Therapeutic range: 20-80 ng/mL

Toxic level: not well established

Therapeutic range: not well established

Proposed dose-related range: 20-60 ng/mL

Toxic range: not well established

Predose draw (trough) preferred:

  • Therapeutic range: 70-170 ng/mL
  • Toxic level: >1,000 ng/mL

Peak draw (1.5 hr post dose; not recommended):

  • Therapeutic range: 100-1,000 ng/mL
  • Toxic level: >1,500 ng/mL

Therapeutic range: 20-60 ng/mL

Toxic range: not well established

Therapeutic range: 50-200 ng/mL

Toxic level: >400 ng/mL

Monitor patient adherence and exposure

Therapeutic range:  0.5-1.2 mmol/L

Toxic level: ≥1.6 mmol/L

Immunosuppressant Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Immunosuppressive Drug Optimization and Monitoring topic.)

Optimize drug therapy and monitor patient adherence

Therapeutic range: 100-400 ng/mL

Kidney transplant (in combination with Everolimus)

  • 1 mo posttransplant: 100-200 ng/mL
  • 2-3 mos posttransplant: 75-150 ng/mL
  • 4-5 mos posttransplant: 50-100 ng/mL
  • 6-12 mos posttransplant: 25-50 ng/mL

Heart transplant

  • Up to 3 mos posttransplant: 350-525 ng/mL
  • 4 mos and older posttransplant: 145-350 ng/mL

Liver transplant: 290-525 ng/mL

Toxic level: >700 ng/mL

Renal transplant (suggested target range): 800-1,700 ng/mL

Liver transplant (suggested target range): 600-1,000 ng/mL

Therapeutic range:

Kidney transplant (in combination with cyclosporine): 3-8 ng/mL

Liver transplant (in combination with tacrolimus):  3-8 ng/mL

Toxic level: >15 ng/mL

Therapeutic range:

Low dose: 0.5-1 µmol/L

High dose/24 hrs: ≤5 µmol/L

48 hrs: ≤0.5 µmol/L

72 hrs: ≤0.1 µmol/L

Mycophenolic acid

  • Therapeutic range: 1-3.5 µg/mL
  • Toxic level: >25 µg/mL

Mycophenolic acid glucuronide

  • Therapeutic range: 35-100 µg/mL
  • Toxic level: not well established

Therapeutic range:

  • Kidney transplant (in combination with cyclosporine): 4-12 ng/mL

Toxic level: >25 ng/mL

Therapeutic range

Kidney transplant

  • 0-3 mos posttransplant: 7-20 ng/mL
  • 3 mos and older: 5-15 ng/mL

Heart transplant

  • 0-3 mos posttransplant: 10-20 ng/mL
  • 3 mos and older: 5-15 ng/mL

Liver transplant

  • 1-12 mos posttransplant: 5-20 ng/mL

Toxic level: >25 ng/mL

Therapeutic monitoring and evaluating full elimination of the drug (eg, toxicity, pregnancy)

Therapeutic range: 50-100 µg/mL (>40 µg/mL associated with improved individual outcome)

Toxic level: not well established

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, RBC

6-thioguanine (6-TG): >235 pmol/8 x 10(8) RBC associated with leucopenia

6-methylmercaptopurine (6-MMP): >5,700 pmol/8 x 10(8) RBC may be associated with hepatoxicity

Miscellaneous Tests

Therapeutic monitoring and evaluating full elimination of the drug (eg, toxicity, pregnancy)

Therapeutic range: 50-100 µg/mL (>40 µg/mL associated with improved individual outcomes)

Toxic level: not well established

Optimize drug therapy and monitor patient adherence

Therapeutic ranges

  • 0-5 mos: 6-12 µg/mL
  • 6 mos and older: 10-20 µg/mL

Toxic level:

  • 0-5 mos: >20.1 µg/mL
  • 6 mos and older: >25.1 µg/mL

Nonopioid Pain Medication Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Pain and Addiction Management topic.)

Aid in the assessment of acetaminophen toxicity

Critical values:

  • Post 4-hr ingestion: >150 µg/mL
  • Post 12-hr ingestion: >40 µg/mL

Optimize drug therapy and monitor patient adherence

Aid in assessment of the etiology of anion gap acidosis

Analgesic: 2-10 mg/dL
Anti-inflammatory: 10-30 mg/dL
Toxic level: ≥31 mg/dL or greater 

Oncology/Chemotherapy Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration.

Optimize dose, detect variable pharmacokinetics, and monitor patient adherence

Concentrations associated with an improved response:

  • Chronic myelogenous leukemia: >1,000 ng/mL
  • Gastrointestinal stromal tumor:  >1,100 ng/mL

Monitor methotrexate concentration

Low dose: 0.5-1 µmol/L

High dose:

  • 24 hrs: ≤5 µmol/L
  • 48 hrs: ≤0.5 µmol/L
  • 72 hrs: ≤0.1 µmol/L

Optimize drug therapy

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, RBC

6-TG: >235 pmol/8 x 10(8) RBC associated with leucopenia

6-MMP: >5700 pmol/8 x 10(8) RBC may be associated with hepatoxicity

Opiate/Opioid Analgesic Tests

The therapeutic range is based on serum predose (trough) draw at steady-state concentration. (Note: Also refer to ARUP Consult’s Pain and Addiction Management  topic.)

Monitor patient adherence

Therapeutic range 2 ng/mL for the following:

Codeine

​Morphine

6-acetylmorphine

Hydrocodone

Hydromorphone

Oxycodone

Oxymorphone

Sedative-Hypnotics Tests

(eg, benzodiazepines, barbiturates, muscle relaxants)

The therapeutic range is based on serum predose (trough) draw at steady-state concentration

Optimize drug therapy and monitor patient adherence

Dose-related ranges:

  • Anxiety: 10-40 ng/mL (dose, 1-4 mg/d)
  • Phobia and panic: 50-100 ng/mL (dose, 6-9 mg/d)

Toxic level: >100 ng/mL

See individual drug analytes for therapeutic ranges and toxic thresholds

Carisoprodol, Serum or Plasma

  • Therapeutic range: <8 µg/mL
  • Toxic level: ≥8 µg/mL

Meprobamate, Serum or Plasma

  • Therapeutic range: 5-20 µg/mL
  • Toxic level: >40 µg/mL

Dose-related range (adult): 20-70 ng/mL (1-8 mg/d)

Toxic level: >80 ng/mL

Dose-related range: 100-1,500 ng/mL (based on common dosage amounts)

Toxic level: >2,500 ng/mL

Diazepam

  • Dose-related range: 200-1,000 ng/mL (based on normal dosage amounts)

Nordiazepam

  • Dose-related range: 100-1,500 ng/mL (based on normal dosage amounts)
  • Toxic level: >2,500 ng/mL

Librium

  • Therapeutic range: 500-3,000 ng/mL (based on adult dose of 5-100 mg)
  • Toxic level: >5,000 ng/mL

Nordiazepam

  • Therapeutic range: 100-1,500 ng/mL (based on normal dosages)
  • Toxic level: >2,500 ng/mL

Dose-related range: 50-240 ng/mL (based on adult dose 1-10 mg/d)

Toxic level: >300 ng/mL

Therapeutic range:

  • Sedation: 1-5 µg/mL
  • Intracranial pressure therapy: 25-35 µg/mL
  • Coma: 10-50 µg/mL

Toxic level: >10 µg/mL

Prazepam

  • Dose-related range: 20-60 mg/d

Nordiazepam

  • Dose-related range: 100-1,500 ng/mL
  • Toxic level: >2,500 ng/mL

Optimize drug therapy and monitor patient adherence

See individual drug analytes for therapeutic ranges and toxic thresholds

Screening test for benzodiazapines

Results are unconfirmed and are to be used for medical (treatment) purposes only

Monitor patient adherence and exposure

Optimize drug therapy and monitor patient adherence

Medical Experts

Contributor
Contributor

McMillin

Gwendolyn A. McMillin, PhD
Gwendolyn A. McMillin, PhD
Professor of Clinical Pathology, University of Utah
Scientific Director, Mass Spectrometry Platform; Medical Director, Clinical Toxicology and Pharmacogenomics, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®

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