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Methotrexate and anticonvulsants

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Methotrexate toxicity with anticonvulsants (antiseizure medicines)

 

  • some antiseizure medicines including levetiracetam, phenytoin and sodium valproate reduce the clearance of methotrexate leading to increased blood levels of methotrexate
    • leads to an increased risk of toxicity

 

  • reduced antiseizure efficacy
    • are case reports of decreased efficacy of phenytoin and sodium valproate when given with methotrexate
    • risks of these interactions are greater at high doses of methotrexate

 

  • liver toxicity
    • co-administration of methotrexate and antiseizure medicines together can increase the risk of liver toxicity

 

Suggested management options (1):

 

  • routine monitoring of methotrexate should detect any signs of methotrexate or liver toxicity
    • inform the specialist looking after methotrexate therapy if antiseizure medicines are started
    • monitor for any changes in seizure activity
  • counsel the person to report signs of methotrexate toxicity, for example sore throat, mouth ulcers, unexplained bruising or bleeding

Reference:

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

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