méthotrexate

Méthotrexate is a folate antagonist used as a chemotherapy agent and as a disease-modifying antirheumatic drug (DMARD). It inhibits dihydrofolate reductase, disrupting nucleotide synthesis and thereby reducing the replication of rapidly dividing cells. At low doses, it also promotes anti-inflammatory effects through mechanisms that include increased extracellular adenosine.

Medical uses include high-dose methotrexate regimens for certain cancers, such as acute lymphoblastic leukemia, osteosarcoma, and some lymphomas, often with hydration and leucovorin (folinic acid) rescue to limit toxicity. At low doses, methotrexate is a standard DMARD for autoimmune diseases, notably rheumatoid arthritis, psoriatic arthritis, and psoriasis, and is used in juvenile idiopathic arthritis and some inflammatory bowel diseases.

Administration and pharmacokinetics vary by indication. Methotrexate can be given orally, subcutaneously, intramuscularly, or intravenously. It is mainly excreted by the kidneys, and its half-life depends on dose and renal function. Folic acid supplementation is commonly used to reduce common adverse effects, while high-dose regimens employ leucovorin rescue to mitigate toxicity.

Adverse effects and monitoring are important considerations. Common effects include mucositis, nausea, and fatigue; serious risks include hepatotoxicity, bone marrow suppression, and pulmonary toxicity. Long-term use increases the risk of liver disease, and toxicity is worsened by alcohol use and pre-existing liver or kidney disease. Contraindications include pregnancy and breastfeeding, significant liver or kidney disease, blood dyscrasias, and active infection. Monitoring typically involves regular blood counts, liver and kidney function tests, and, for women of childbearing potential, pregnancy testing.

Safety and regulatory status: Méthotrexate requires close medical supervision and is prescribed under specific dosing regimens that reflect its dual cytotoxic and immunomodulatory roles.