Methotrexate: Drug Interactions and Toxicity

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- Contraindications:
      - Septra (Bone marrow toxicity)
      - Probenecid (blocks tubular secretion of methotrexate)

- GI Toxicity:
      - GI intolerance is the most common adverse reaction;
      - anorexia, nausea, vomiting, diarrhea, and even unexplained wt loss

- Bone Marrow Toxicity:
      - may occur and is usually associated w/ following
      - risk factors:
              - renal insufficiency
              - folic acid depletion
              - use of concomitant trimethoprim/sulfamethoxazole;
      - supplemental folic acid (1 mg/day) may reduce the risk of hematologic toxicity without interfering with efficacy;

- Toxic Effects on the Liver
      - manifested by fever, abdominal pain, diarrhea, & maculopapular skin rash;
      - look for elevated LFT's;

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