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Methotrexate: Drug Interactions and Toxicity

- 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