Methotrexate
Note: this site is for informational purposes only. To view test results or book a test, use the NHS app in England or contact your GP.
A methotrexate test measures the level of the drug methotrexate in the blood using a blood sample taken from a vein in the arm. It is used to monitor treatment, particularly high-dose therapy, helping to guide dosing and reduce the risk of toxicity by determining the need for interventions such as leucovorin rescue.
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.
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.
Common questions
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.
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
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.
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.
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.
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.
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).
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.