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Key Points

  • Methotrexate (Trexall)
    • Mechanism
      • Folic acid antagonist (anti-folate)
        • Prevents DNA replication (S-phase) needed for cell replication, since folic acid is required for creation of thymidine
    • Clinical use
      • Cancer / Chemotherapy
        • Leukemias
        • Head and neck cancer
        • Breast and ovarian cancer
        • GI tract cancer
      • Immunosuppressant/Anti-inflammatory Drug
        • Rheumatoid arthritis
          • Anti-inflammatory DMARD (disease modifying antirheumatic drug) that slows progression of disease
        • Psoriasis (psoriatic arthritis)
      • Ectopic pregnancies
    • Side Effects and Adverse Reactions
      • Hepatotoxicity
        • Instruct patient to avoid alcohol
        • Monitor liver enzymes
        • Contraindicated in patients with liver failure and alcoholism
      • Bone marrow depression (myelosuppression)
        • Can lead to anemia (low red blood cells)
          • Fatigue, dyspnea, pallor
        • Can lead to leukopenia (low white blood cells)
          • Increased risk for infection
          • Live vaccines are contraindicated, but inactivated vaccines are highly recommended (flu, pneumococcal, etc.)
          • Avoid crowds and people with known infections
        • Can lead to thrombocytopenia (low platelets)
          • Petechiae, purpura, bleeding
        • Contraindicated in patients with blood dyscrasias
      • GI Disturbances
        • Nausea, vomiting, anorexia, diarrhea
        • Stomatitis (inflammation of mouth + oral ulcers)
        • Expected side effect that can be minimized with folic acid supplementation
          • Advise the patient to consult with their doctor before taking folic acid supplements. Folic acid alters the body’s response to methotrexate, but may be prescribed to reduce GI irritation.
      • Teratogenic
        • Folic acid antagonism can lead to birth defects in the fetus, especially neural tube defects (e.g. spina bifida, etc.)
        • Patients should take extreme caution to not become pregnant while on methotrexate or for 3 months following discontinuation of drug