Methotrexate: English spelling of Methotrexat (folic acid antagonist)
Methotrexate is the internationally used English spelling of Methotrexat (abbreviated MTX). Both refer to the same active ingredient, a folic acid antagonist from the group of antimetabolites. In the German-speaking area, the English form is encountered primarily in original publications, international guidelines (EULAR, ACR), study names, and on packaging of imported preparations. There is no difference in content between Methotrexate and Methotrexat. We have provided comprehensive information under /wirkstoff/methotrexat. This page summarizes the key facts and guides you to the German main page.
MTX was first used in 1947 in pediatrics to treat acute lymphoblastic leukemia and remains one of the most important drugs in oncology, rheumatology, and dermatology today. In rheumatology, MTX is used as an anchor DMARD (disease modifying antirheumatic drug), while in oncology it is used at high doses for leukemia, lymphoma, and osteosarcoma. Important to know: The dosages differ by up to two orders of magnitude, and confusion between weekly rheumatology doses and daily administration is one of the most frequently reported medication errors in Germany.
Mechanism of action
Methotrexate competitively inhibits the enzyme dihydrofolate reductase (DHFR) and thereby blocks the conversion of dihydrofolate to tetrahydrofolate. Tetrahydrofolate is a cofactor in the synthesis of thymidylate and purine bases, i.e., in DNA synthesis. Due to folic acid deficiency, cell proliferation slows down, particularly in rapidly dividing cells such as tumor cells, lymphocytes, and skin cells.
In low-dose rheumatological application, a different effect is in the foreground: MTX inhibits AICAR transformylase and leads to accumulation of adenosine, a potent endogenous anti-inflammatory agent. This anti-inflammatory effect explains why MTX in rheumatoid arthritis, already at weekly doses of 7.5 to 25 mg, slows pain and joint destruction without producing significant cytostatic activity.
Bioavailability after oral administration ranges between 30 and 80 percent and decreases with increasing dose. Subcutaneous administration improves absorption and drug efficacy, which is why it is often preferred when there is insufficient response to tablets. MTX is eliminated predominantly renally, which is why renal insufficiency significantly increases plasma levels and thus toxicity.
Indications
- Rheumatology: rheumatoid arthritis (first-line DMARD), psoriatic arthritis, juvenile idiopathic arthritis, spondyloarthropathies with peripheral involvement
- Dermatology: moderate to severe psoriasis vulgaris, atopic eczema off-label
- Gastroenterology: Crohn's disease (maintenance of remission), autoimmune hepatitis off-label
- Oncology high-dose: acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, CNS lymphoma (intrathecal administration)
- Gynecology: treatment of tubal pregnancy (ectopic pregnancy)
Dosage and administration
Rheumatology and dermatology: 7.5 to 25 mg once weekly orally, subcutaneously, or intramuscularly. The weekly dose must never be administered daily. Folic acid 5 to 10 mg is substituted 24 to 48 hours after MTX to reduce mucositis, elevated liver enzymes, and nausea. The effect occurs with a delay after six to twelve weeks.
Oncology: High-dose regimens of 1 to 12 g/m² body surface area under inpatient conditions with calcium folinate rescue, hyperhydration, and urine alkalinization. This therapy is administered exclusively in specialized centers. In patients with impaired renal function (eGFR below 60 ml/min), caution is advised. MTX is contraindicated from eGFR below 30 ml/min.
Side effects
Common: nausea, vomiting, oral mucositis (stomatitis), fatigue on the day of administration, hair thinning, elevated transaminases, leukopenia, and anemia.
Occasional to rare: hepatotoxicity up to hepatic fibrosis with long-term use, MTX pneumonitis (acute dyspnea with fever, can occur at any stage of therapy), bone marrow suppression, renal function deterioration.
Important: MTX is teratogenic and embryotoxic. In women, therapy must be discontinued at least one month before planned pregnancy. In men, a three-month wash-out period is discussed according to current EULAR recommendations. Safe contraception is required during therapy.
Drug interactions
- NSAIDs (ibuprofen, diclofenac, naproxen): displace MTX from plasma protein binding and reduce renal excretion; usually tolerable in low rheumatology doses but dangerous in high-dose therapy
- Cotrimoxazole (trimethoprim/sulfamethoxazole): additive folic acid antagonism; risk of severe bone marrow suppression
- Proton pump inhibitors: delay MTX elimination, particularly relevant in high-dose therapy
- Penicillins: reduce MTX clearance
- Live vaccines: contraindicated under immunosuppressive therapeutic doses
- Alcohol: enhances hepatotoxicity, should be avoided if possible
Special precautions
Pregnancy and breast-feeding: contraindicated. MTX is abortifacient and teratogenic. If pregnancy occurs during therapy, reproductive medical consultation is urgently required. MTX is not approved during breast-feeding.
Monitoring: blood count and liver transaminases every four to eight weeks, creatinine every three months, lung function annually if clinically suspected. Patients receive an MTX card with notation of the weekly dose to prevent the most common source of confusion (daily instead of weekly).
Vaccinations: Inactivated vaccines (influenza, COVID-19, pneumococcal) are approved and recommended under MTX. Live vaccines (MMR, varicella, yellow fever) should be administered before starting therapy.
You might also be interested in
- Methotrexat, the comprehensive German main page
- Folinic acid, the antidote in high-dose MTX
- Leflunomide, alternative DMARD
- Sulfasalazine, another basic therapeutic agent
- Adalimumab, biological DMARD for MTX failure
Frequently asked questions
Is Methotrexate the same as Methotrexat?
Yes. Methotrexate is the English spelling, Methotrexat is the form commonly used in German-speaking countries. Both refer to exactly the same active ingredient (folic acid antagonist, ATC L01BA01). On imported packaging or in English studies, you will usually find the form with an e at the end.
Why do I only take MTX once a week?
The anti-inflammatory effect in rheumatism and psoriasis lasts throughout the week, while the mucosa and bone marrow recover between doses. Daily administration would lead to severe bone marrow suppression and mucositis. Accidental daily administration is a known source of error in Germany and is recorded via the CIRS reporting system.
Why does my doctor additionally give folic acid?
Folic acid (5 to 10 mg, 24 to 48 hours after MTX) demonstrably reduces nausea, oral mucositis, and elevated liver enzymes, without significantly reducing efficacy. EULAR recommends substitution as standard.
Can I drink alcohol while taking MTX?
Both stress the liver. International guidelines recommend drastically reducing or completely avoiding alcohol, especially in the first months of therapy and in patients with pre-existing liver disease.
Sources
- Gelbe Liste, Methotrexat active ingredient profile
- AWMF Guidelines for Rheumatoid Arthritis and Psoriasis
- BfArM, Dear Healthcare Provider Letter Methotrexate (dosing warning)
- EMA Product Information Methotrexate preparations
Legal notice and disclaimer
The information provided on this page is for general information purposes only and does not constitute medical advice, diagnosis, or treatment recommendation. It does not replace the advice of a licensed physician or pharmacist. Medications should only be taken as prescribed by a physician or dispensed by a pharmacist. All statements are based on product information published at the time of creation and recognized scientific sources. The current product information from the manufacturer is authoritative. Sanoliste assumes no liability for completeness, currency, or accuracy of the information presented. In case of medical emergency, call emergency number 112.