Methotrexate is a chemotherapy and immunosuppressant drug used to treat both cancer and autoimmune diseases.
Overview
- Class: Antimetabolite (specifically, a folate antagonist)
- Mechanism of Action:
- Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme involved in the synthesis of DNA, RNA, and proteins. This blocks the formation of tetrahydrofolate, leading to impaired DNA replication and cell division—especially in rapidly dividing cells.
Uses
Cancer Treatment
Leukemias (especially acute lymphoblastic leukemia [ALL]), Lymphomas, Breast cancer, Osteosarcoma, Choriocarcinoma, Head and neck cancers
Autoimmune & Inflammatory Conditions
Rheumatoid arthritis (RA), Psoriasis, Lupus, Inflammatory bowel disease (occasionally), Ectopic pregnancy (used to terminate pregnancy non-surgically by stopping trophoblastic tissue growth)
How It’s Given
Oral, Intravenous (IV), Intramuscular (IM), Intrathecal (injected into spinal fluid for CNS prophylaxis in leukemia)
Side Effects
- Bone marrow suppression (low blood counts)
- Liver toxicity (elevated liver enzymes, fibrosis with long-term use)
- Mouth ulcers (mucositis)
- Nausea and fatigue
- Pulmonary toxicity (rare, but serious)
- Kidney damage at high doses
- Teratogenicity (causes birth defects — absolutely contraindicated in pregnancy)
Special Considerations
- Folic acid supplementation: Patients taking methotrexate for autoimmune diseases are often given folic acid to reduce side effects.
- Leucovorin rescue: In high-dose cancer treatments, leucovorin (folinic acid) is used to “rescue” healthy cells from the effects of methotrexate.
- Drug interactions: NSAIDs, penicillins, and others can increase methotrexate levels and toxicity.