Methotrexate

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Also known as: MTX [Often referred to by brand name (see MedlinePlus Drug Information)]

Formal name: Methotrexate

Related tests: CBC, BUN, Creatinine, Liver Panel, Therapeutic Drug Monitoring

At a Glance

Why Get Tested?

To detect and evaluate toxic concentrations of methotrexate

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; when having your blood drawn, tell the laboratorian when you took your last dose of methotrexate.

The Test Sample

What is being tested?

This test measures the amount of methotrexate in the blood. Methotrexate is a drug that has been in use since the 1960s. It is primarily used to treat childhood acute lymphocytic leukemia, lymphoma, cancers of the lung, head, neck, and breast, and is also prescribed to treat rheumatoid arthritis (RA) and psoriasis. Methotrexate interferes with the vitamin folate, which slows the growth of cancer cells and decreases immune system activity. It acts as an anti-inflammatory and can help minimize the joint damage associated with RA.

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.

The dose of methotrexate given depends upon the condition being treated. It is usually given once a week, with levels in the blood rising after a dose and then gradually falling. 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.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed, but timing of the sample for testing is important and the doctor may specify collection at a certain number of hours after a methotrexate dose.

The Test

How is it used?

High-dose methotrexate therapy is monitored with one or more methotrexate tests that are typically ordered at 24 hours, 48 hours, and as needed at 72 hours after a person's methotrexate dose. Testing is performed to detect 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.

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When is it ordered?

A methotrexate test is typically ordered at 24 hours, 48 hours, and at 72 hours as needed after high-dose methotrexate is administered. Tests to monitor blood cell counts and kidney and liver function are also ordered at regular intervals during methotrexate therapy. The test is rarely ordered to monitor low-dose methotrexate; it may be collected at 30 minutes or 2 hours after the dose. A methotrexate test may also be ordered whenever a person has symptoms or signs that suggest methotrexate toxicity.

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

Nausea
Thinning hair
Mouth sores
Fatigue
Diarrhea
Sensitivity to sunlight
Headaches

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

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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 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.

With high-dose methotrexate, toxic concentrations are generally considered to be:

≥ 5 µmol/L at 24 hours after the dose
≥ 0.5 µmol/L at 48 hours
≥ 0.055 µmol/L at 72 hours

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.

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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 ibuprofen, phenytoin, theophylline, digoxin, sulfadiazine, warfarin, and certain antibiotics. These substances may need to be avoided, or the dosages of methotrexate and other medications may need to be adjusted.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates (aspirin) can interfere with the clearance of methotrexate. Excessive alcohol use can increase the risk of methotrexate-associated liver damage.

Methotrexate must not be taken while a woman is pregnant or breast-feeding.

Doctors may perform blood tests to assess kidney and liver function and blood cell counts prior to initiating methotrexate therapy.

Sensitivity to methotrexate and associated side effects increase with age.

Response to methotrexate therapy varies. Some of the variation in effectiveness and toxicity is thought to be due to genetic variations. This concept is being researched and may lead to the clinical use of one or more genetic tests to help predict a person's response to methotrexate.

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Common Questions

1. Why would my doctor recommend a folate supplement when I am taking methotrexate?

Some of the side effects associated with methotrexate use are due to decreased folate levels. Doctors may recommend folate supplementation to help minimize symptoms.

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2. Do I need to let my other doctors know that I am taking methotrexate?

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

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3. What else is methotrexate used for?

Although it is most commonly used as treatment for cancer 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's disease, asthma, and systemic lupus erythematosus.

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4. 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.

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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

(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 at http://www.medscape.com/druginfo/patienthandout?cid=med&drugid=3441&drugname=Methotrexate+%28Anti-Rheumatic%29+Oral&monotype=patienthandout 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 through http://www.medscape.com. 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 through http://www.medscape.com. 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 through http://www.mayoclinic.com. 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 through http://www.medscape.com. 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 through http://www.rheumatology.org. Accessed April 2010.