USMLE

Methotrexate

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Anti-Neoplastic Drugs
  1. Cyclophosphamide
  2. Methotrexate
  3. Tamoxifen
  4. Cisplatin
  5. Doxorubicin
  6. Imatinib
  7. Paclitaxel
  8. Rituximab
  9. Trastuzumab
  10. Vincristine

Summary

Methotrexate is a medication that works by blocking or inhibiting folate. This blocks cell division, which can be used to kill rapidly-dividing cells. Due to this, methotrexate is often used as a chemotherapy to treat various forms of cancer. It is also used for its anti-inflammatory effects to treat autoimmune diseases like rheumatoid arthritis. Side effects of methotrexate include hepatotoxicity, bone marrow suppression, and gastrointestinal disturbances, including stomatitis. Folic acid supplements may help alleviate severe GI side effects, but remind patients to consult with their doctor beforehand. Finally, methotrexate is teratogenic and should not be taken by pregnant women.

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