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Dihydrofolate Reductase Inhibitors

    Oral / IV
    Weekly dosing


    • Mechanism of Action

    • Inflammatory diseases: inhibits interleukin-1 and interleukin 6 activity, and altering the numbers of different lymphocyte subsets.
    • In cancer treatment: inhibits dihydrofolate reductase (DHFR), reducing synthesis of folate, which is involved in synthesis of the purine and pyramidine precursors required for DNA / RNA and cell proliferation.
    • Pharmacology

    • Serum half-life 8 hours
    • Renal excretion - caution in combination with NSAIDs

Clinical Use

    • Indications

    • Inflammatory diseases - refractory inflammatory bowel disease, rheumatoid arthritis, psoriasis
    • Chemotherapy - for certain cancers
    • Adverse Effects

    • Gastrointestinal - mouth ulcers, nausea / vomiting / abdominal pain
    • Hepatotoxicity - elevated LFTs, cirrhosis
    • Pulmonary - hypersensitivity pneumonitis
    • Bone marrow suppression - leukopaenia / thrombocytopaenia / anaemia
    • Monitoring

    • Monthly full blood count, renal function and LFTs.
Last updated on November 19th, 2019


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