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Published on: November 8, 2015

Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen

A Thyss, G Milano, J Kubar

    Lancet (London, England)
    |February 1, 1986
    PubMed

    Insights

    Concurrent use of ketoprofen with high-dose methotrexate (MTX) can cause severe toxicity, even death. Ketoprofen should not be given within 12 hours of high-dose MTX to avoid dangerous drug interactions.

    Area of Science:

    • Oncology
    • Pharmacology
    • Clinical Toxicology

    Background:

    • High-dose methotrexate (MTX) is a critical chemotherapy agent.
    • Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain management.

    Purpose of the Study:

    • To investigate the potential interaction between ketoprofen and high-dose methotrexate.
    • To assess the impact of ketoprofen co-administration on methotrexate toxicity.

    Main Methods:

    • Retrospective analysis of 118 high-dose methotrexate cycles in 36 patients.
    • Identification of cycles where ketoprofen was co-administered.
    • Evaluation of methotrexate toxicity and serum levels in relation to ketoprofen timing.

    Main Results:

    • Ketoprofen was co-administered in 4 of 118 cycles.
    • All 4 cycles with ketoprofen showed severe methotrexate toxicity, with 3 fatalities.
    • Simultaneous ketoprofen administration led to prolonged, enhanced serum MTX levels.
    • No toxicity observed when ketoprofen was given ≥12 hours after MTX infusion.

    Conclusions:

    • Simultaneous administration of ketoprofen and high-dose methotrexate poses a significant risk of severe toxicity.
    • The kidney is a potential site for this drug interaction.
    • This interaction highlights a potential risk with other NSAIDs and high-dose MTX therapy.

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