• Also Known As:
  • MTX
  • Amethopterin
Medically Reviewed by Expert Board

This page was fact checked by our expert Medical Review Board for accuracy and objectivity. Read more about our editorial policy and review process.

This article was
last modified The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.
Learn more about...

At a Glance

Why Get Tested?

  • To detect, monitor and evaluate toxic concentrations of methotrexate
  • To measure methotrexate levels in blood to determine the initial dosage requirement in individuals with immune disease

When To Get Tested?

At specific timed intervals after a high dose of methotrexate to monitor blood levels and guide treatment and whenever symptoms suggest methotrexate toxicity

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None, but timing of the sample for testing is important; your healthcare practitioner may specify collection at a certain number of hours after a methotrexate dose; when having your blood drawn, tell the person collecting your blood sample when you took your last dose of methotrexate.

You may be able to find your test results on your laboratory’s website or patient portal. However, you are currently at Lab Tests Online. You may have been directed here by your lab’s website in order to provide you with background information about the test(s) you had performed. You will need to return to your lab’s website or portal, or contact your healthcare practitioner in order to obtain your test results.

Lab Tests Online is an award-winning patient education website offering information on laboratory tests. The content on the site, which has been reviewed by laboratory scientists and other medical professionals, provides general explanations of what results might mean for each test listed on the site, such as what a high or low value might suggest to your healthcare practitioner about your health or medical condition.

The reference ranges for your tests can be found on your laboratory report. They are typically found to the right of your results.

If you do not have your lab report, consult your healthcare provider or the laboratory that performed the test(s) to obtain the reference range.

Laboratory test results are not meaningful by themselves. Their meaning comes from comparison to reference ranges. Reference ranges are the values expected for a healthy person. They are sometimes called “normal” values. By comparing your test results with reference values, you and your healthcare provider can see if any of your test results fall outside the range of expected values. Values that are outside expected ranges can provide clues to help identify possible conditions or diseases.

While accuracy of laboratory testing has significantly evolved over the past few decades, some lab-to-lab variability can occur due to differences in testing equipment, chemical reagents, and techniques. This is a reason why so few reference ranges are provided on this site. It is important to know that you must use the range supplied by the laboratory that performed your test to evaluate whether your results are “within normal limits.”

For more information, please read the article Reference Ranges and What They Mean.

What is being tested?

Methotrexate is a drug that is used to treat childhood acute lymphocytic leukemia, lymphoma, and cancers of the lung, head, neck, and breast as well as rheumatoid arthritis and psoriasis. This test measures the amount of methotrexate in the blood.

Methotrexate prevents cells from using folate to make DNA and RNA, slowing growth of new cancer cells. Because it can also deter growth of new skin cells, methotrexate is also used to treat psoriasis. The drug blocks several enzymes involved in the immune system and can minimize joint damage associated with rheumatoid arthritis.

Methotrexate must be carefully monitored. Even when used correctly, it can cause significant side effects. Increased concentrations can be toxic, potentially damaging the liver, kidneys, and lungs and suppressing cell production in the bone marrow.

Methotrexate dosing depends upon the condition being treated. Methotrexate levels in the blood typically rise after a dose and then fall gradually. Methotrexate is eliminated from the body by the kidneys, so any condition that decreases kidney function or interferes with drug clearance has the potential to increase blood concentrations.

Common Questions

How is it used?

High-dose methotrexate therapy is monitored at regular intervals following a methotrexate dose. Testing detects toxic concentrations of methotrexate at these time points. A drug called leucovorin (folinic acid) can be given as a “rescue” treatment to protect a person from the toxic effects of methotrexate. The methotrexate test series identifies the need for leucovorin and guides the timing and amount of its administration.

Low-dose methotrexate therapy is rarely monitored by a methotrexate test. It is usually monitored by assessing the function of the kidney, the liver, and bone marrow cell production. Testing may include a complete blood count (CBC) to measure red blood cell counts, white blood cell counts, and platelets; a blood urea nitrogen (BUN) and creatinine to evaluate kidney function; and a liver panel (or one or more of its component tests) to evaluate liver function.

When is it ordered?

A methotrexate test is typically ordered at regular intervals (e.g., at 24 hours, 48 hours, and at 72 hours as needed) after administration of high-dose methotrexate. Tests to monitor blood cell counts and kidney and liver function are also ordered at regular intervals during methotrexate therapy.

A methotrexate test may also be ordered whenever a person has symptoms or signs that suggest methotrexate toxicity. It is rarely ordered in conjunction with low-dose methotrexate therapy.

Common side effects associated with methotrexate use (that may be seen without toxic concentrations of methotrexate) include:

  • Nausea
  • Thinning hair
  • Mouth sores, tender gums
  • Fatigue
  • Diarrhea
  • Sensitivity to sunlight
  • Headaches
  • Trouble sleeping
  • Low blood counts

More serious signs and symptoms seen with methotrexate toxicity include:

  • Dark stools or urine
  • Bruising and bleeding
  • Drug-induced hepatitis
  • Cough
  • Fever and chills
  • Shortness of breath
  • Chest pain
  • Abdominal pain
  • Bacterial septicemia
  • Severe skin rash
  • Seizures

What does the test result mean?

With therapeutic drug monitoring, there is typically a “therapeutic range,” with a lower limit that is associated with effectiveness and an upper limit associated with unacceptable side effects and toxicity. With high-dose methotrexate, the primary focus is on an upper limit – toxicity, the drug’s effect on the kidney, liver, and blood cell counts, and on unacceptable side effects.

Test results are used to guide the amount and timing of leucovorin (folinic acid) given as a “rescue” treatment.

Low-dose methotrexate is rarely monitored with a methotrexate test. The therapeutic concentration of the drug depends upon the condition and the timing of the blood collection.

Although the risks of side effects and organ damage increase with increasing levels of methotrexate, a person may experience side effects from methotrexate use without having high blood levels of the drug.

Is there anything else I should know?

A variety of prescription and over-the-counter medications and supplements can interfere or interact with methotrexate, including aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs), phenytoin, retinol, theophylline, digoxin, sulfadiazine, warfarin, certain antibiotics, and vitamin E. Tell your healthcare practitioner about all prescription and over-the-counter medications and supplements that you take.

Excessive alcohol use can increase the risk of methotrexate-associated liver damage.

Methotrexate is eliminated from the body through the kidneys; thus, any kidney dysfunction will result in diminished release of methotrexate out of the body.

Sensitivity to methotrexate and associated side effects increase with age, while individuals’ response to methotrexate therapy varies. Some of the variation in effectiveness and toxicity is thought to be due to genetic variations. Researchers are examining this idea and it may eventually lead to the clinical use of one or more genetic tests to help predict a person’s response to methotrexate.

Why would my healthcare provider recommend a folate supplement when I am taking methotrexate?

Some of the side effects associated with methotrexate use, such as increase in the plasma concentration of homocysteine, are due to decreased folate levels. Healthcare practitioners may recommend folate supplementation to help minimize symptoms.

Do I need to let my other healthcare providers know that I am taking methotrexate?

Yes, this is important information for all your healthcare providers, including your dentist, to have. This is because of possible drug interactions and because methotrexate suppresses your immune system.

What else is methotrexate used for?

Although it is most commonly used as treatment for cancer, sever psoriasis, and rheumatoid arthritis, methotrexate is sometimes used as a treatment for ectopic (tubal) pregnancies and may be prescribed for conditions such as multiple sclerosis, Crohn disease, asthma, and lupus.

Why do I need to avoid live vaccines while I am taking methotrexate?

Live vaccines contain weakened microorganisms that are intended to stimulate a person’s immune system to create antibodies for protection against a specific infection. Since methotrexate depresses the immune system, the body’s immune system is less able to respond appropriately.

View Sources

Sources Used in Current Review

2018 review completed by Mahesheema Ali, Ph.D.

(April 16, 2016) Methotrexate Blood Test, DoveMed. Available online at https://www.dovemed.com/common-procedures/procedures-laboratory/methotrexate-blood-test/?reload. Accessed on 04/08/2018.

MedlinePlus Drug Information, Methotrexate. Available online at https://medlineplus.gov/druginfo/meds/a682019.html. Accessed on 04/08/2018.

(March 2018) Methotrexate, Uptodate. Available online at https://www.uptodate.com/contents/use-of-methotrexate-in-the-treatment-of-rheumatoid-arthritis. Accessed on 4/08/2018.

Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23nd ed. McPherson R, Pincus M, eds. Philadelphia, PA: Saunders Elsevier: 2017.

Sources Used in Previous Reviews

(Revised 2009 April 1). Methotrexate. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682019.html. Accessed April 2010.

(Reviewed 2008 September 1). Methotrexate Injection. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682018.html. Accessed April 2010.

(Revised 2009 July). Patient Education, METHOTREXATE – ORAL. Medscape [On-line information]. Available online through http://www.medscape.com. Accessed April 2010.

Rotondo, N. (2008 August 13). When Is it Appropriate to Use Methotrexate for Ectopic Pregnancy in the Emergency Department? Medscape Today [On-line information]. Available online at http://www.medscape.com/viewarticle/576935. Accessed April 2010.

Ranganathan, P. (2008 July 14). An Update on Methotrexate Pharmacogenetics in Rheumatoid Arthritis. Medscape Today from Pharmacogenomics. 2008;9(4):439-451. [On-line information]. Available online at http://www.medscape.com/viewarticle/576224. Accessed April 2010.

(Updated 2009 November 1). Methotrexate (Oral Route, Injection Route). MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/drug-information/DR600919. Accessed April 2010.

Brauna, J. and Rau, R. (2009 July 29). An Update on Methotrexate. Medscape from Curr Opin Rheumatol. 2009;21(3):216-223.[On-line information]. Available online at http://www.medscape.com/viewarticle/706105. Accessed April 2010.

Cannon, M. (Updated 2009 August). Methotrexate (Rheumatrex, Trexall). American College of Rhematology [On-line information]. PDF available for download at http://www.rheumatology.org/practice/clinical/patients/medications/methotrexate.pdf. Accessed April 2010.

Pagana, K. D. & Pagana, T. J. (© 2007). Mosby’s Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 361-364.

Clarke, W. and Dufour, D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 462-463.

Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 1400-1403.

Methotrexate. American Cancer Society. Available online at http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/methotrexate. Last revised December 29, 2011. Accessed January 10, 2014.

Methotrexate (Rheumatrex, Trexall). American College of Rheumatology. Available online at http://www.rheumatology.org/Practice/Clinical/Patients/Medications/Methotrexate_(Rheumatrex,_Trexall)/. Last updated May 2012. Accessed January 10, 2014.

Methotrexate for psoriasis. WebMd. Available online at http://www.webmd.com/skin-problems-and-treatments/psoriasis/methotrexate-for-psoriasis. Last updated November 9, 2010. Accessed January 10, 2014.

Methotrexate (Injection Route, Subcutaneous Route). Mayo Clinic. Available online at http://www.mayoclinic.org/drugs-supplements/methotrexate-injection-route-subcutaneous-route/description/DRG-20064776. Last updated December 1, 2013. Accessed January 10, 2014.

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.

Ask a Laboratory Scientist