Methotrexate and penicillins

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