Patient Test Information


Also known as:

MTX [Often referred to by brand name (see MedlinePlus Drug Information)]

Formal name:


Related tests:

Complete Blood Count, BUN, Creatinine, Liver Panel, Therapeutic Drug Monitoring

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.

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
  • 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. These substances may need to be avoided, or the dosages of methotrexate and other medications may need to be adjusted.

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

Methotrexate may cause sterility.

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

Tell your health practitioner if you have or have had any of these conditions, which may preclude use of the drug or warrant caution:

  • Alcohol abuse
  • Anemia
  • Leukopenia
  • Liver disease
  • Thrombocytopenia
  • Weakened immune system (immunocompromised)
  • Ascites (extra fluid in the stomach area)
  • Kidney disease
  • Pleural effusion (extra fluid in the lung)
  • Diabetes
  • Liver disease
  • Obesity
  • Peptic ulcers
  • Ulcerative colitis (inflammation of the colon)
  • Past radiation or chemotherapy
  • Bacterial, fungal, or viral infection

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.

What is being tested?

Methotrexate is a drug that has been in use since the 1960s to treat childhood acute lymphocytic leukemia, lymphoma, and cancers of the lung, head, neck, and breast. 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 (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.

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.

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 a health practitioner may specify collection at a certain number of hours after a methotrexate dose.

  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.

  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.

  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, Crohns disease, asthma, and systemic lupus erythematosus.

  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.