Methotrexate
Key Points
- Methotrexate (MTX) is a folate antagonist antimetabolite used in both oncology and autoimmune disease management.
- Inhibits dihydrofolate reductase, blocking DNA synthesis in rapidly dividing cells.
- Used at high doses for cancer treatment and at lower doses as a DMARD for rheumatoid arthritis.
- Requires close monitoring for bone marrow suppression, hepatotoxicity, and nephrotoxicity.
Mechanism of Action
Methotrexate inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and thymidylate needed for DNA replication. By blocking folate metabolism, methotrexate prevents cell division in rapidly proliferating cells. At lower doses, it also suppresses immune system activity, providing anti-inflammatory effects in autoimmune conditions.
Indications
- Cancer chemotherapy (leukemias, lymphomas, breast cancer, head and neck cancers).
- Rheumatoid arthritis (low-dose weekly regimen).
- Psoriasis (severe, recalcitrant cases).
- Ectopic pregnancy management.
Nursing Considerations
- Monitor CBC with differential regularly; bone marrow suppression (leukopenia, thrombocytopenia, anemia) is the most common serious toxicity.
- Monitor liver function tests; cumulative hepatotoxicity can lead to fibrosis and cirrhosis.
- Monitor renal function; methotrexate is primarily excreted renally.
- Leucovorin (folinic acid) rescue may be prescribed to reduce toxicity in high-dose regimens.
- Methotrexate is a teratogen; verify negative pregnancy status before initiation and ensure reliable contraception.
- Avoid concurrent use with NSAIDs, which can increase methotrexate toxicity by reducing renal clearance.
- Teach infection-prevention measures because of immunosuppression risk.
Side Effects and Adverse Effects
- Common: Nausea, vomiting, stomatitis (oral mucositis), fatigue, anorexia.
- Hematologic: Bone marrow suppression — leukopenia, thrombocytopenia, anemia.
- Hepatic: Elevated liver enzymes, hepatic fibrosis, cirrhosis with cumulative exposure.
- Renal: Nephrotoxicity, crystalluria.
- Pulmonary: Pneumonitis (rare but serious).
Bone Marrow Suppression
Methotrexate can cause life-threatening pancytopenia. Monitor CBC regularly and report signs of infection, unusual bleeding, or severe fatigue immediately.
Health Teaching
- Take methotrexate exactly as prescribed (often weekly for autoimmune conditions, not daily).
- Report mouth sores, unusual bleeding or bruising, persistent cough, or signs of infection promptly.
- Avoid alcohol, which increases hepatotoxicity risk.
- Use reliable contraception; methotrexate causes birth defects.
- Avoid live vaccines during therapy.
Related Concepts
- antimetabolites - Broader chemotherapeutic drug class context.
- disease-modifying-antirheumatic-drugs - DMARD use in rheumatoid arthritis.
- immunosuppressants - Immune suppression context and infection-risk teaching.
Self-Check
- Why is leucovorin rescue used with high-dose methotrexate therapy?
- What is the dosing difference between methotrexate for cancer and for rheumatoid arthritis?
- Why must NSAIDs be avoided or used cautiously with concurrent methotrexate therapy?