metotrexat

Metotrexat, commonly known as methotrexate in English, is a folate analog antimetabolite used in cancer chemotherapy and as a disease-modifying antirheumatic drug (DMARD). It inhibits dihydrofolate reductase, reducing the production of tetrahydrofolate and thereby impairing DNA, RNA, and protein synthesis. The drug can also promote adenosine release, contributing to anti-inflammatory effects in autoimmune diseases.

In oncology, metotrexat is used to treat acquired or pediatric cancers such as acute lymphoblastic leukemia, certain lymphomas, osteosarcoma, choriocarcinoma, and cancers of the head and neck. It may be given systemically or directly into the central nervous system, depending on the disease. In high-dose regimens, leucovorin rescue is used to mitigate toxicity.

In rheumatology and dermatology, methotrexate is a first-line or widely used DMARD for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, and severe psoriasis. It is also used off-label for other inflammatory conditions.

Administration approaches include oral, intramuscular, subcutaneous, intravenous, or intrathecal routes. Pharmacokinetics vary with dose and route; clearance is influenced by renal function. Patients on high-dose regimens require careful monitoring and folinic acid (leucovorin) rescue to reduce toxicity.

Adverse effects include myelosuppression, mucositis, liver enzyme elevations or hepatotoxicity, nephrotoxicity, pulmonary toxicity, and gastrointestinal symptoms. Teratogenicity is a major concern; methotrexate is generally avoided in pregnancy. Common drug interactions include NSAIDs, certain antibiotics, and other antifolate medications, which can increase toxicity or alter clearance.

Due to potential severe toxicity, methotrexate therapy is regulated and guided by clinical protocols, with regular laboratory monitoring and dose adjustments.