Therapeutic Drug Monitoring

What is therapeutic drug monitoring (TDM)?

Therapeutic drug monitoring is the measurement of specific drugs and/or their breakdown products (metabolites) at timed intervals to maintain a relatively constant concentration of the medication in the blood. Some of the monitored drugs tend to have a narrow “therapeutic index,” which is a ratio between the toxic and therapeutic (effective) dose of medication.

As soon as a drug enters the body, different processes start removing the drug from the body. The amount of time it takes for the body to reduce the drug concentration to half from the initial value is called a half-life of the drug. It generally takes around five half-lives to remove a drug completely from the body.

Generally, a person must be given a drug dose at regular intervals to ensure that the effective or the therapeutic concentration of the drug is maintained in the body. For some drugs, maintaining this steady state is not as simple as giving a standard dose of medication. Each person will absorb, metabolize, utilize and eliminate drugs at different rates based upon their age, general state of health and genetic makeup. The drug concentration in the body may be enhanced or decreased by the interference of other medications that you may be taking along with the drug which has to be motioned. This is also known as drug-drug interaction.

Not all medications require therapeutic monitoring. Most drugs have a wide therapeutic index and can be prescribed based upon pre-established dosing schedules. The effectiveness of these treatments has been evaluated, but monitoring the concentration of the drug in the blood is not required for dosing. Examples of drugs that do not require monitoring include high blood pressure (hypertension) medications and many of the antibiotics given to treat bacterial infections. If an infection resolves with a given antibiotic or if blood pressure is lowered with the prescribed blood pressure medication, then the treatments have been effective.

Common Questions

Why is TDM important?

Many of the drugs that require therapeutic monitoring are taken for a lifetime. They must be maintained at steady concentrations year after year while the person ages and goes through life events that may alter that individual’s therapeutic level, including pregnancies, temporary illnesses, infections, emotional and physical stresses, accidents, and surgeries. Over time, people may acquire other chronic conditions that also require lifetime medication and that may affect the processing of their monitored drugs. Examples of these conditions include cardiovascular disease, kidney disease, thyroid disease, liver disease, and HIV.

Therapeutic drug monitoring follows these changes and accommodates them. It identifies when a person does not take the medication regularly as prescribed (patient noncompliance) and the effect of drug interactions, which may cause drug concentrations that are higher or lower than expected at a given dosage, and helps to personalize a dose to fit the specific needs of a patient. Along with tests such as BUN, creatinine, and liver function tests, therapeutic drug monitoring can help identify decreases in the efficiency of and dysfunctions in the body’s ability to metabolize and eliminate therapeutic drugs. Testing may also determine how a medication interacts with other necessary drugs.

How are these tests used?

Not all drug levels need to be monitored. These tests are used to monitor blood levels of drugs that have a narrow range in which the drug is effective but not toxic. In addition, some drugs require monitoring because the amount of drug given does not correlate well with the amount of drug that may reach the blood. Sometimes, the way that a drug is absorbed and metabolized can vary from person to person, or the physical or health status of a person can affect the drug level in the blood.

Through years of testing, the optimum therapeutic ranges for drugs have been determined. In these ranges, most people will be effectively treated without excessive side effects or symptoms of toxicity. The drug dosage necessary to reach this level must be determined for everyone. When a person starts on a monitored drug (or returns to it after an absence), the health practitioner adjusts the dose upwards and tests blood concentrations frequently until the appropriate steady level is achieved. If someone’s levels are too high, the health practitioner will lower the dosage. Often, each different dosage level will take a short period of time to stabilize, so these corrections up and down may take place over a few days or weeks. It is important that people work closely with their health practitioner during this process and not make their own adjustments or stop taking their medication. Abrupt changes can sometimes worsen conditions and cause acute symptoms.

When are they ordered?

Levels of monitored drugs are often tested frequently when a person is first put on a drug regimen. Once a person’s results are in the therapeutic range and his or her clinical signs indicate that the treatment is appropriate, then the health practitioner may monitor the drug at regular intervals and as needed to accommodate changes in patient status and to ensure that the drug stays in the therapeutic range. The frequency of testing required will depend on the drug and on the needs of the patient. If treatment does not appear to be fully effective, or if the person has either excessive side effects or signs of toxicity, then the health practitioner will order testing aimed at adjusting the drug dosage and maintaining levels within the therapeutic range. Sometimes, the health practitioner may need to re-evaluate the use of a specific medication and consider switching to another type of drug to better fit the person’s condition.

The timing of blood collection is an important part of therapeutic drug monitoring. When a person takes a dose of drug, the amount in the blood rises for a period, peaks, and then begins to fall, usually reaching its lowest level, or trough, just before the next dose. To be effective, peak levels should be below toxic concentrations and trough levels should remain in the therapeutic range. Through experience and studies, health practitioners know when to expect peaks and troughs and will request blood sample collections as either trough levels (usually drawn just before the next dose), peak levels (for which timing varies depending on the drug), or sometimes as a randomly timed level. Consistent and accurate interpretation of the results depends on the timing of sample collection. If someone is unable to take his or her medication or have blood drawn at the appropriate time interval, then he or she should talk to their health practitioner before the sample is collected.

How does a healthcare practitioner determine how much drug to give me?

There are many factors to consider. Some of them are your weight, body composition, age, and general health and nutritional status. Other factors to consider are if you have any acute or chronic conditions such as kidney, liver, or heart conditions, of if you have suffered burns, shock, or trauma. Your health practitioner takes these into account when prescribing a dosage quantity and frequency and then tailors your medication based upon the results of therapeutic monitoring.

Can I monitor myself at home?

No. Blood must be collected at specific times and tests must be performed using special laboratory equipment.

What should I do if I forget to take my medication on time?

Do not double your dose the next time. Consult your health practitioner or pharmacist to find out what you should do.

Monitored Drugs by Category

There are several categories of drugs that require monitoring, as summarized here.
Drug Category	Drugs	Treatment Use
Cardiac drugs	Digoxin, digitoxin, amiodarone, lidocane, quinidine, procainamide, N-acetyl-procainamide (a metabolite of procainamide)	Congestive heart failure, angina, arrhythmias
Antibiotics	Aminoglycosides (gentamicin, tobramycin, amikacin), vancomycin, chloramphenicol	Infections with bacteria that are resistant to less toxic antibiotics
Antiepileptics	Phenobarbital, phenytoin, valproic acid, carbamazepine, ethosuximide, sometimes gabapentin, lamotrigine, levetiracetam, topiramate, zonisamide, eslicarbazepine acetate, felbamate, lacosamide, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, vigabatrin	Epilepsy, prevention of seizures, sometimes to stabilize moods
Bronchodilators	Theophylline, caffeine	Asthma, chronic obstructive pulmonary disorder (COPD), neonatal apnea
Immunosuppressants	Cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, azathioprine	Prevent rejection of transplanted organs, autoimmune disorders
Anti-cancer drugs	Methotrexate, all cytotoxic agents	Psoriasis, rheumatoid arthritis, various cancers, non-hodgkin lymphomas, osteosarcoma
Psychiatric drugs	Lithium, valproic acid, some antidepressants (imipramine, amitriptyline, nortriptyline, doxepin, desipramine)	Bipolar disorder (manic depression), depression

Related Image

How drugs enter and are processed through the body. Image credit: NIH

View Sources

Sources Used in Current Review

2018 review completed by Jasbir Singh Arora, PhD, NRCC.

Dasgupta A. Therapeutic Drug Monitoring. Newer Drugs and Biomarkers, 1st Edition (June 21, 2012) Elseiver.

Katzung B, Trevor A, Masters S. Basic and Clinical Pharmacology, 14 edition (November 30, 2017) McGraw Hill.

Pincus MR, Bluth MH, Abraham NZ. Toxicology and therapeutic drug monitoring. In: McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St Louis, MO: Elsevier Saunders; 2017:chap 23.

Sources Used in Previous Reviews

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. AIDS Info. Available online at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed January 9, 2014. Last updated February 13, 2013.

Therapeutic Drug Levels. MedlinePlus Medical Encyclopedia. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003430.htm. Last updated May 12, 2011. Accessed January 7, 2013.

Therapeutic Drug Monitoring (TDM). Quest Diagnostics. Available online at https://www.questdiagnostics.com/home/physicians/testing-services/condition/toxicology/tdm-info. Copyright © 2000-2014 Quest Diagnostics Incorporate. Accessed January 7, 2014.

Management Options: Drug Therapy Requiring Intensive Monitoring for Toxicity. Palmetto GBA Medicare Part B OH/WV/SC. Available online through http://www.palmettogba.com. Issued July 2009. Accessed January 9, 2013.

Commonly monitored drugs. Siemens. Available online at http://www.healthcare.siemens.com/clinical-specialities/therapeutic-drug-monitoring/commonly-monitored-drugs. Accessed January 9, 2013.

Clinical Chemistry: Principles, Procedures, Correlations. Bishop M, Duben-Engelkirk J, Fody E, eds. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2000.

National Academy of Clinical Biochemistry. Guidelines for Therapeutic Drug Monitoring Services. Edited by Ann Warner and Thomas Annesley. Available online at http://www.nacb.org/nacb_publications.stm.

Larry A. Broussard, PhD. Clinical Laboratory Sciences, LSU Health Sciences Center, New Orleans, LA.

Catherine A. Hammett-Stabler, PhD.

Thomas, Clayton L., Editor (1997). Taber’s Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby’s Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. Pp 814-817.

Greco, F. (2005 October 27, Updated). Therapeutic drug levels. MedlinePlus Medical Encyclopedia: [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003430.htm.

Bottorff, M. (© 2005) Toxicology, Clinical Pharmacokinetics and Therapeutic Drug Monitoring. ARUP’s Guide to Clinical Laboratory Testing [On-line information]. Available online at http://www.aruplab.com/guides/clt/tests/clt_fr15.jsp.

Laboratory for Antiviral Research at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences: HIV Drug Interactions and TDM Registry. Available online at http://tdm.buffalo.edu/.

Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns DE, eds. St. Louis: Elsevier Saunders; 2006, Pp. 1237-1239, 1247-1248.

Henry’s Clinical Diagnosis and Management by Laboratory Methods. 21st ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2007, 308-309.

Johns Hopkins POC-IT Center. Therapeutic Drug Monitoring, Antiretroviral therapy. Available online at http://www.hopkins-aids.edu/management/antiretroviral_therapy/therapeutic_drug_monitoring.html?contentInstanceId=8259&siteId=7151. Accessed May 2010.

Tomson T, Dahl ML, Kimland E. Therapeutic monitoring of antiepileptic drugs for epilepsy. Cochrane Database Syst Rev. 2007; Medline abstract. Available online at http://www.medscape.com/medline/abstract/17253477. Accessed May 2010.

Ask a Laboratory Scientist

This form enables patients to ask specific questions about lab tests. Your questions will be answered by a laboratory scientist as part of a voluntary service provided by one of our partners, American Society for Clinical Laboratory Science. Please allow 2-3 business days for an email response from one of the volunteers on the Consumer Information Response Team.