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This article waslast modified on 5 October 2020.
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 concentrations and guide treatment, and whenever symptoms suggest methotrexate toxicity

Sample Required?

A blood sample taken from a vein in your arm

Test Preparation Needed?

None, but timing of the sample for testing is important; when having your blood taken, tell the healthcare professional when your last dose of methotrexate was taken or given.

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you may be able to access your results online. Your GP practice will be able to provide specific details.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, sex, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

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 leukaemia and, some lymphomas. In adults, it is used for: cancers of the lung, head, neck, and breast, non-Hodgkin's lymphoma and is also prescribed to treat rheumatoid arthritis (RA), severe Crohn's disease and psoriasis. Methotrexate interferes with the vitamin folate. This action slows the growth of cancer cells and decreases immune system activity. Methotrexate also acts as an anti-inflammatory drug and can help minimise 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. Low-dose therapy for non-cancer conditions 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 excretion has the potential to increase blood concentrations.

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Common Questions
  • How is it used?

    High-dose methotrexate therapy used in cancer treatment is monitored with one or more methotrexate blood tests that are typically requested at 24 hours, 48 hours, and as needed at 72 hours after a person's methotrexate dose has been administered. 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 blood tests help to identify the need for leucovorin and guides the timing and amount of its administration.

    Low-dose methotrexate therapy is rarely monitored by a methotrexate blood test. It is usually monitored by assessing the function of the kidney, the liver, and bone marrow cell production. Testing may include a Full Blood Count (FBC) to measure red blood cell counts, white blood cell counts, and platelets; a blood urea and creatinine to evaluate kidney function; and liver function tests to evaluate liver function. The development of liver fibrosis on long-term treatment may also be evaluated with a blood test called procollagen III N-terminal peptide (P3NP), which is normally checked annually.

  • When is it requested?

    A methotrexate test is typically requested 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 requested at regular intervals during methotrexate therapy. The test is rarely used to monitor low-dose methotrexate. A methotrexate blood test may also be requested 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:

    • Loss of appetite
    • Nausea or vomiting
    • Thinning hair
    • Sore mouth/mouth ulcers
    • Fatigue
    • Diarrhoea
    • Sensitivity to sunlight
    • Headaches

    More serious signs and symptoms seen with methotrexate toxicity include:

    • Dark stools or urine
    • Jaundice
    • Bruising and bleeding
    • Drug-induced hepatitis
    • Cough
    • Sore throat
    • Fever and chills
    • Shortness of breath
    • Chest pain
    • Abdominal pain
    • Bacterial septicaemia
    • Severe skin rash
    • Seizures
  • What does the test result mean?

    With therapeutic drug monitoring, there is typically a "therapeutic range”, with a lower concentration limit that is associated with effectiveness and an upper limit associated with unacceptable side effects and toxicity. In the case of methotrexate, the primary focus is on the upper concentration limit – the drug's toxic effects on the kidney, liver, and blood cell counts, and on unacceptable side effects.

    When methotrexate is given in high doses, toxic concentrations are generally considered to be:

    above 5 µmol/L at 24 hours after the dose

    above 0.5 µmol/L at 48 hours

    above 0.05 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 therapy is rarely monitored with a methotrexate blood 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 doses of methotrexate, a person may experience side effects from methotrexate use without having high blood concentrations 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: phenytoin, theophylline, digoxin, ciclosporin, warfarin, omepraxole, diuretics and certain antibiotics (trimethoprim, co-trimoxazole). 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) such as ibuprofen and salicylates (aspirin) can reduce the excretion 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. It is important to avoid getting pregnant or fathering a child while taking methotrexate, and for 6 months afterwards (consult your doctor).

    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.

  • 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 protect healthy cells in your body and minimise symptoms like nausea and diarrhoea.

  • Do I need to let other health care professionals 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.

  • 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, asthma, and systemic lupus erythematosus (SLE).

  • 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.