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Methotrexate, usually abbreviated as MTX, is the gold standard in rheumatology and the most important first-line drug for rheumatoid arthritis. About 1% of adults in Germany have rheumatoid arthritis, above all women from 40 (a German figure, broadly similar across Western countries). Unlike almost all other medications, MTX is taken only once a week — an accidental daily intake has already been fatal more than once.
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Methotrexate is taken with autoimmune diseases ONLY ONCE WEEKLY — never daily (life-threatening). Regular laboratory checks are mandatory. MTX is harmful to the unborn child — reliable contraception. Last updated: May 2026.
Methotrexate is the most important base medication of rheumatology — with a unique safety topic: the weekly instead of daily intake. Below are the most important key facts for a quick orientation; the individual points are explained in detail in the following chapters.
| Property | Details |
|---|---|
| Active substance | Methotrexate (MTX) |
| Trade names | Lantarel, Metex, MTX HEXAL, methotrexate generics; as a pre-filled pen e.g. Metoject, Nordimet |
| ATC code | L04AX03 (immunosuppression) / L01BA01 (oncology) |
| Substance class | Folic acid antagonist; DMARD (disease-modifying antirheumatic drug); antimetabolite/cytostatic (in a high dose) |
| Mechanism of action | Inhibition of dihydrofolate reductase + adenosine release → anti-inflammatory (low dose), cell-division-inhibiting (high dose) |
| Administration | Tablet or subcutaneous injection (pre-filled pen) — both forms 1× weekly |
| Usual dose rheumatism | 7.5–25 mg ONCE WEEKLY (never daily!) |
| Onset of effect | Full effect only after 6–8 weeks, sometimes up to 12 weeks |
| Concomitant therapy | Folic acid 5 mg on another day of the week (24–48 h after MTX) |
| Life-threatening confusion | Daily instead of weekly intake — documented deaths |
| Excretion | Predominantly renal — renal insufficiency raises the toxicity risk |
| Prescription status | Yes |
| Most important note | Weekly intake + folic acid + regular laboratory checks + reliable contraception (women AND men) |
Methotrexate — mostly abbreviated as MTX — is a versatile medication with a fascinating double role: in a low dose it is the most important and most frequently used base medication (DMARD) with rheumatoid arthritis and other autoimmune diseases. In a high dose it is a classic cytostatic in cancer therapy. This double role is central to the understanding of the medication.
Methotrexate was originally developed in the 1940s as a cancer medication. Only later was the excellent effect in a much lower dose with autoimmune diseases discovered — since the 1980s, low-dose MTX has been the gold standard in rheumatology. It is today taken worldwide by millions of people with rheumatoid arthritis, psoriasis, and other inflammatory diseases.
Important to understand — and the most dangerous aspect of this medication: with autoimmune diseases, methotrexate is taken only once a week, not daily. This unusual dosing is a common source of serious, partly fatal confusions — which is why we devote a separate chapter to it right at the beginning.
This warning stands at the beginning of this article for a good reason. The weekly intake is an absolute exception in everyday medication — almost all other medications are taken daily. Precisely this deviation makes MTX so error-prone. Typical confusion scenarios: patients or relatives who do not know the dosing; new carers; hospital admissions in which the weekly scheme is overlooked; patients with cognitive impairments.
The only exception to the weekly rule is the high-dose therapy in oncology, which takes place by completely different, strictly monitored protocols in the hospital — that has nothing to do with the home rheumatism therapy.
Methotrexate is a folic acid antagonist — it resembles folic acid (vitamin B9) structurally and blocks the enzyme dihydrofolate reductase, which is necessary for the conversion of folic acid into its active form. Folic acid in turn is essential for DNA synthesis and cell division. Through the inhibition, MTX intervenes in the metabolism of rapidly dividing cells.
It is interesting that the anti-inflammatory effect at a low dose is not explained by the folic acid inhibition alone. A central role is played by the release of adenosine — a body's own anti-inflammatory substance. MTX in a low dose thereby works immunomodulating and anti-inflammatory, without suppressing the immune system as strongly as a classic cytostatic. That explains the good effect with autoimmune diseases.
Methotrexate is well absorbed at a low oral dose (incompletely at higher doses — one reason for the injection). The excretion takes place predominantly via the kidneys — therefore a sufficient kidney function is essential and a renal insufficiency an important risk factor for poisonings. The effect on the disease builds up slowly — the full effect only sets in after 6 to 8 weeks.
One of the most important distinctions for understanding methotrexate — the two uses are so different that they hardly appear as the same medication:
| Aspect | Low dose (rheumatism/dermatology) | High dose (oncology) |
|---|---|---|
| Dose | 7.5–25 mg once a week | Up to several grams per m² body surface (100- to 1000-fold higher) |
| Goal | Anti-inflammation, immunomodulation | Killing of cancer cells |
| Use | At home, orally or as a self-injection | In the hospital as an infusion under strict monitoring |
| Concomitant therapy | Folic acid for side-effect reduction | "Rescue" with folinic acid (leucovorin), to protect healthy cells |
| Monitoring | Regular blood checks (blood count, liver, kidney) | Intensive level checks, hydration, urine alkalinisation |
This article predominantly treats the low-dose therapy, which takes place at home and is relevant for most patients. The high-dose oncology is a strictly hospital-based specialist therapy.
The most important indication. With rheumatoid arthritis, methotrexate is the first-choice base medication (anchor DMARD). It slows the joint destruction, reduces inflammation and pain, and can change the course of the disease sustainably. Often the basis for combination therapies with biologics.
With moderate to severe psoriasis and psoriatic arthritis, MTX is an established base medication that improves both the skin manifestations and the joint involvement.
With Crohn's disease, MTX is used as an immunosuppressant, above all when other base medications are not sufficient.
MTX is also used with juvenile idiopathic arthritis (children), connective tissue diseases, vasculitides, and other inflammatory-rheumatic diseases — often as a central building block of the base therapy.
In a high dose, MTX is used with various cancer diseases — leukaemias, lymphomas, certain solid tumours. This use takes place exclusively in the oncological specialist setting.
The dosing with autoimmune diseases is set individually and raised slowly. Always once weekly:
An essential building block of the MTX therapy that often raises questions: since methotrexate inhibits the folic acid metabolism, a relative folic acid deficiency arises — which is responsible for many of the typical side effects (nausea, inflammation of the oral mucosa, hair loss, blood count changes). The accompanying administration of folic acid reduces these side effects clearly, without substantially impairing the effectiveness of MTX.
Important distinction: folic acid is the concomitant therapy with low-dose MTX. Folinic acid (leucovorin), on the other hand, is the "emergency antidote" with an MTX overdose or in high-dose oncology — that is not the same and not interchangeable.
Methotrexate can be administered with the low-dose therapy as a tablet or as a subcutaneous injection (an injection under the skin, similar to insulin). Both forms have advantages and disadvantages:
| Form | Advantages | Disadvantages | Suitable for |
|---|---|---|---|
| Tablet (oral) | Simple, no injection necessary | Absorption in the bowel incomplete and varying at higher doses | Low doses (up to about 15 mg/week) |
| Subcutaneous injection (pre-filled pen) | Better and more constant absorption, fewer gastrointestinal side effects, higher effectiveness at the same dose | An injection necessary (self-administrable, pre-filled pens available) | Higher doses (from about 15 mg/week) or with gastrointestinal intolerance |
Many patients begin with tablets and are switched to the injection with a higher dose need or stomach complaints. The self-injection is well achievable after a short instruction. The decision is made individually by the treating doctor.
Methotrexate in a low dose is well controllable with good monitoring — side effects are common, but mostly manageable, above all with accompanying folic acid:
Most of these side effects are dose-dependent and well reducible through folic acid, a dose adjustment, or a switch to the injection.
Methotrexate requires careful monitoring, because rare but serious side effects can occur:
MTX can suppress the blood formation in the bone marrow — with a reduction of white blood cells (a risk of infection), red blood cells (anaemia), and blood platelets (a risk of bleeding). Regular blood count checks are therefore mandatory. Warning signs: fever, unusual bleeding, pronounced weakness.
With long-term use, MTX can damage the liver (up to liver fibrosis). Regular liver value checks and the avoidance of alcohol are essential.
Since MTX is excreted via the kidneys, a restricted kidney function can lead to accumulation and poisoning. Regular checking of the kidney values, a dose adjustment with renal insufficiency.
| Time point | Examinations |
|---|---|
| Before the start of therapy | Blood count, liver and kidney values, hepatitis serology, chest X-ray, pregnancy test |
| In the initial phase | Blood count, liver, kidney every 2 weeks |
| With a stable setting | Checks every 8–12 weeks |
| Permanently | Lifelong regularly — the monitoring belongs inseparably to the MTX therapy |
