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Updated: Jan 28, 2026

Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Fatal Flaw in the Folate Pathway: Methotrexate-Bactrim Interaction, Misleading Levels, and a Cautionary Case
1Internal Medicine, East Carolina University, Greenville, USA.
Abstract:
Methotrexate (MTX) is one of the most commonly prescribed medications for rheumatoid arthritis and other autoimmune disorders. While therapeutic drug monitoring (TDM) protocols are well-established for high-dose MTX (HD-MTX) in oncology, no such validated protocols exist for low-dose MTX (LD-MTX) therapy - the pharmacokinetics are highly variable, and serum concentrations correlate poorly with clinical toxicity. Among the most dangerous drug interactions is the combination of MTX with trimethoprim-sulfamethoxazole (TMP-SMX), which creates synergistic toxicity. This case details a rapid, fatal MTX toxicity event in a patient on stable LD therapy who received a short course of TMP-SMX for cellulitis. Severe pancytopenia and hemorrhagic oral mucositis developed despite a serum MTX concentration of 0.07 μmol/L - well below the commonly accepted toxic threshold. This case underscores that clinicians must prioritize prompt recognition of clinical symptoms over laboratory quantification when risk factors for drug interaction are present.
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