Methotrexate
immunosuppressant / antimetabolite
Third-party optionBy the Layer Nutrition editorial team · How the atlas classifies the 664 molecules
What this medicine is for
Methotrexate is a medicine in the category "immunosuppressant / antimetabolite". This medicine modulates or slows the immune system, in an autoimmune disease or after a transplant; it requires close monitoring.
For Methotrexate, in practice: Treats certain autoimmune inflammatory diseases and certain cancers. It is most often a long-term treatment, taken at set times over long periods; its benefit is judged over time, not by how you feel on a given day.
Under which brands it is found
In France, about 13 reimbursable presentations containing Methotrexate are recorded. It is found under several brand names and as generics.
- Imeth
- Izixate
- Methotrexate Accord
- Methotrexate Teva
- Methotrexate Viatris
- Metoject
- Metotab
- Nordimet
- Imenor
- and other presentations
Original brand-name products and generics deliver the same active substance; the choice between them is made with your doctor or pharmacist.
On your plate: folate
Methotrexate is a folate antagonist: it blocks dihydrofolate reductase and lowers the availability of active tetrahydrofolate. Your doctor prescribes folic acid for this reason, and dietary folates help replenish the same reserves.
Folates are concentrated in green leafy vegetables such as spinach and broccoli, in legumes, citrus fruits, liver and eggs. These foods provide the natural form of vitamin B9, the one the body uses to build DNA nucleotides and renew its cells.
Regularly putting a serving of green vegetables, lentils or beans and a citrus fruit on your plate covers a good part of your folate needs, alongside your treatment. Diet remains the easiest lever to keep up over the weeks, without replacing the supplementation your doctor has set.
How methotrexate works
Methotrexate enters cells through the reduced folate carrier, SLC19A1, the same entry gate as natural vitamin B9. Once inside, it undergoes polyglutamation, which retains it within the cell and strengthens its action. It then inhibits dihydrofolate reductase, the enzyme that converts dihydrofolate into active tetrahydrofolate. Without this tetrahydrofolate, the cell can no longer make the nucleotides of DNA and RNA. In its polyglutamated form, methotrexate also blocks thymidylate synthase, another key enzyme of DNA synthesis.
In autoimmune diseases, at low doses, another mechanism dominates. Methotrexate inhibits AICAR transformylase, which leads to an accumulation of adenosine around cells. This adenosine slows the activation of T lymphocytes and reduces the function of B lymphocytes. It is this pathway that explains the anti-inflammatory effect sought against rheumatoid arthritis, distinct from the antiproliferative effect used in oncology.
Why methotrexate is prescribed
Methotrexate occupies two quite different areas depending on the dose. At a low weekly dose, it serves as a disease-modifying treatment for inflammatory conditions: rheumatoid arthritis, juvenile idiopathic arthritis and psoriasis. It calms inflammation and slows joint or skin damage over time.
At a high dose, it becomes a chemotherapy agent. It is then indicated in several leukaemias and lymphomas, breast cancer, head and neck cancers and gestational trophoblastic tumours. The same drug therefore completely changes its role depending on the prescription regimen, which explains why the dose and the timing are set with such precision.
How to take it day to day
For autoimmune diseases, methotrexate is taken only once a week, as a single dose or split over the day. This weekly rhythm is the most important safety rule of the treatment. People who took it once a day instead of once a week have experienced very serious side effects, sometimes fatal. The day of intake is chosen and kept the same from one week to the next, to anchor the reference point.
The doctor almost always prescribes folic acid alongside it, at a rate of 1 mg per day or 5 to 7 mg per week, in order to prevent bone marrow toxicity and reduce certain side effects. Methotrexate is not stopped on your own, even when symptoms subside: its long-term effect rests on continuity. Any change in the rhythm or the dose goes through the doctor.
The effects to know about and their frequency
The most frequent side effects are digestive: nausea, vomiting, ulceration of the mucous membranes of the mouth and loss of appetite. The liver is the organ to monitor closely. Under a low or medium dose taken over several months, a rise in transaminases, ALT or AST, occurs in 15 to 50% of patients, most often mild and transient; about 5% exceed twice the upper normal limit. Over the longer term, nearly 30% of patients develop mild to moderate histological liver abnormalities and 2 to 20% some degree of fibrosis.
With modern regimens, that is 5 to 15 mg in a single weekly dose with folate supplementation, fibrosis and clinically apparent liver damage remain rare, even over time. The serious effects to be aware of include hepatotoxicity, bone marrow suppression, infections, kidney failure and teratogenicity. Methotrexate is classified as category X and contraindicated during pregnancy because of its effect on the fetus.
The nutritional side: folates
Methotrexate is a folate antagonist. By inhibiting dihydrofolate reductase, it reduces the availability of tetrahydrofolate and its derivatives, and thus deprives thymidylate synthase of its substrates. This action is also the source of most of its side effects, because tissues that renew quickly, bone marrow and mucous membranes, depend on folates. The drug is among those that interfere with the use of folates and can contribute to a deficiency.
This is why folic acid supplementation accompanies the treatment. The concomitant administration of about 1 mg per day reduces the frequency of liver enzyme elevations, without reducing the efficacy of methotrexate. In case of toxicity, it is another form, folinic acid or leucovorin, that serves as rescue treatment. Dietary folates are found mainly in green leafy vegetables such as spinach and broccoli, legumes, citrus fruits, liver and eggs.
Interactions and monitoring
Several common medicines increase the risk of methotrexate toxicity. NSAIDs, salicylates and proton pump inhibitors modify its renal elimination and can raise its blood concentrations. Drugs strongly bound to plasma proteins can displace it, since it too binds about 50% to these proteins. Methotrexate is eliminated mainly by the kidney, and its half-life ranges from 3 to 10 hours at low doses up to 8 to 15 hours after a high-dose course.
Laboratory monitoring frames the treatment. It combines a blood count, serum creatinine and transaminases, carried out every week during the first 4 weeks, then at least twice a month. This monitoring makes it possible to detect early any damage to the marrow, kidney or liver and to adjust the dose. It is an integral part of the treatment, just like the weekly intake itself.
Sources
Related molecules
To explore in the « Pain and inflammation » family and its neighbours.
See the whole « Pain and inflammation » family · Back to the atlas
Supplements to consider
Beyond the plate, a single isolated nutrient can be worth discussing, to confirm with your doctor or pharmacist. Here is which one and in which form.
Folates (vitamine B9)
Folate (vitamin B9) is a water-soluble vitamin. The active form 5-MTHF (5-methyltetrahydrofolate) is directly usable, unlike folic acid, which must be converted by the body.
Preferred form 5-MTHF (methylfolate) rather than folic acid
Frequently asked questions
What is methotrexate used for?
Methotrexate is a medicine used in several situations, in particular certain inflammatory conditions such as rheumatoid arthritis and psoriasis, as well as in oncology. Its indication and monitoring are the responsibility of the doctor who prescribed it. For your specific situation, refer to the package leaflet and to your doctor or pharmacist.
What are the side effects of methotrexate?
The leaflet mentions in particular nausea, digestive problems, mouth ulcers or sores, fatigue, possible hair loss and changes in liver and blood test results that warrant biological monitoring. This list is not exhaustive. For all of the adverse effects and what to do about them, consult the package leaflet and your doctor or pharmacist.
Can you take methotrexate during pregnancy?
The leaflet states that methotrexate is contraindicated during pregnancy and that effective contraception is required during treatment, in women and in men depending on the case. Any plan to conceive should be discussed with the doctor well in advance. Refer to the package leaflet and to your doctor or pharmacist.
Can you drink alcohol while taking methotrexate?
Drinking alcohol is not advised during treatment with methotrexate, because of the strain on the liver noted in the leaflet. The rule that applies to your treatment should be confirmed by your doctor or pharmacist, who take your overall situation into account.
Why is folic acid often taken with methotrexate?
Methotrexate acts as a folate antagonist, and health authorities link this mechanism to the value of folic acid supplementation to reduce certain adverse effects of the treatment, without lowering its efficacy. This combination is carefully framed: folic acid is taken on a different day from methotrexate, never on the same day. The principle, the form and the schedule are for your doctor to decide. Sources: Summary of Product Characteristics (ANSM) and CBIP.
Which form of folate to consider with methotrexate, and what precautions?
The documented reference active is folic acid (folate), in the form of folic acid, to be distinguished from folinic acid, which is sometimes prescribed in other situations. Research also notes that folate intake can mask a vitamin B12 deficiency, hence the value of checking B12 before any supplementation, particularly after age 50. Any intake takes place under strict medical supervision and in coordination with the treatment schedule.
Ces réponses portent sur le volet nutritionnel. Pour toute question sur votre médicament, la notice et votre médecin ou pharmacien font foi.