Methotrexate (MTX): Uses, Dosage & Side Effects
Methotrexate (MTX) is a medication used to treat cancer, rheumatoid arthritis, and psoriasis. It works by inhibiting cell growth and suppressing the immune system.
Things worth knowing about "Methotrexate"
Methotrexate (MTX) is a medication used to treat cancer, rheumatoid arthritis, and psoriasis. It works by inhibiting cell growth and suppressing the immune system.
What is Methotrexate?
Methotrexate (abbreviated as MTX) is a drug used in oncology (cancer medicine), rheumatology, and dermatology. It belongs to the class of antimetabolites and immunosuppressants – substances that inhibit cell division and suppress immune system activity. Methotrexate has been a well-established medication for decades and is one of the most commonly prescribed drugs for autoimmune diseases.
Indications – When is Methotrexate Used?
Methotrexate is used for a wide range of conditions, including:
- Rheumatoid arthritis: As a disease-modifying antirheumatic drug (DMARD) to slow disease progression.
- Psoriasis: For moderate to severe skin psoriasis and psoriatic arthritis.
- Cancer: For example, in certain leukemias, lymphomas, osteosarcomas, and bladder cancers, typically at higher doses.
- Other autoimmune diseases: Including Crohn's disease, lupus erythematosus, and certain forms of vasculitis.
- Ectopic pregnancy: In selected cases as a non-surgical treatment option.
Mechanism of Action
Methotrexate works by inhibiting the enzyme dihydrofolate reductase (DHFR). This enzyme is essential for converting folic acid (vitamin B9) into its active form, which is required for DNA and RNA synthesis – and therefore for cell division. By blocking this enzyme, methotrexate slows or stops the division of rapidly dividing cells, such as:
- Tumor cells (in cancer)
- Immune cells (in autoimmune diseases)
- Skin cells (in psoriasis)
At low doses, as used in rheumatology, methotrexate also promotes the release of adenosine, which contributes to its anti-inflammatory effect.
Dosage
The dosage of methotrexate varies considerably depending on the condition being treated:
- Low-dose (e.g., rheumatoid arthritis, psoriasis): Typically 7.5 to 25 mg once weekly, taken orally (tablets) or by subcutaneous injection.
- High-dose (oncology): Significantly higher doses, often given intravenously, followed by folinic acid (leucovorin) rescue therapy to protect healthy cells.
During low-dose therapy, folic acid supplementation is often recommended to reduce side effects. The exact dosage must always be determined by the treating physician.
Side Effects
Methotrexate can cause a range of side effects, which vary in severity depending on the dose:
Common Side Effects
- Nausea, vomiting, and abdominal pain
- Mouth sores (mucositis, stomatitis)
- Fatigue and malaise
- Elevated liver enzymes
- Hair loss (usually reversible)
Serious Side Effects
- Liver toxicity: Long-term use may lead to liver fibrosis or cirrhosis. Regular monitoring of liver function is therefore essential.
- Bone marrow suppression: Methotrexate can impair blood cell production, potentially causing anemia, leukopenia (low white blood cell count), and thrombocytopenia (low platelet count).
- Pneumonitis: A rare but serious inflammation of the lungs, presenting with cough and shortness of breath.
- Kidney toxicity: Particularly relevant at high doses.
- Teratogenicity: Methotrexate is strictly contraindicated during pregnancy, as it can cause severe harm to the unborn child.
Contraindications and Drug Interactions
Methotrexate must not be used in patients with:
- Pregnancy or breastfeeding
- Severe liver or kidney impairment
- Significant bone marrow damage
- Active infections
Important drug interactions include:
- Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or diclofenac: may reduce the elimination of methotrexate and increase toxicity.
- Trimethoprim/cotrimoxazole: Enhances the effect on bone marrow suppression.
- Alcohol: Significantly increases the risk of liver damage.
Monitoring and Safety
Because methotrexate is a high-risk medication, regular monitoring is essential:
- Full blood count (checking white blood cells, platelets, and hemoglobin)
- Liver function tests (ALT, AST, GGT, bilirubin)
- Kidney function (creatinine, GFR)
- If needed: liver biopsy or elastography
Patients should contact their doctor immediately if they experience symptoms such as fever, severe fatigue, shortness of breath, unusual bleeding, or jaundice.
References
- Smolen JS et al. – EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Annals of the Rheumatic Diseases, 2020.
- European Medicines Agency (EMA) – Methotrexate: Summary of Product Characteristics. www.ema.europa.eu
- Cronstein BN – Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacological Reviews, 2005.
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