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Methotrexate and penicillins

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Methotrexate toxicity

  • penicillins (for example, amoxicillin) may reduce the clearance of methotrexate via the kidneys by competitive inhibition
    • leads to an increased the risk of methotrexate toxicity

Suggested management options (1):

  • if the duration of penicillin is short (up to 10 days), consider using with caution and advise to monitor for signs of toxicity (for example, sore throat, bruising and bleeding)
  • In the presence of a severe acute or chronic infection, some people on stable methotrexate therapy can miss doses of methotrexate whilst taking the course of penicillin antibiotics
    • restart methotrexate once they feel better

Reference:

  1. NHS Specialist Pharmacy Service (June 30th 2025). Managing interactions with methotrexate

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