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Patient Test Information


  • 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.

  • 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.

  • 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.

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    Sources Used in Current Review

    2018 review completed by Mahesheema Ali, Ph.D.

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