To detect and evaluate toxic concentrations of methotrexate
A blood sample taken from a vein in your arm
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.
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, 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 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. 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 excretion 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.
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 has been given.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 has been given.
How is it used?
High-dose methotrexate therapy 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 ihelp to dentify 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:
- Thinning hair
- Mouth sores
- Sensitivity to sunlight
More serious signs and symptoms seen with methotrexate toxicity include:
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:
≥ 5 µmol/L at 24 hours after the dose
≥ 0.5 µmol/L at 48 hours
≥ 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 levels 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, 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) 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.
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?
Do I need to let other health care professionals know that I am taking methotrexate?
What else is methotrexate used for?
Why do I need to avoid live vaccines while I am taking methotrexate?