Does Penicillin Interact With Methotrexate?

In our latest question and answer, the pharmacist discusses whether or not penicillin interacts with methotrexate.

Mar 26, 2018

Lambln asked

I received methotrexate for an ectopic pregnancy on 3/13. I have now been prescribed penicillin v potassium and started it on 3/23 for strep throat. Is there a possibility of drug interaction being that far apart and only taking one dose? Should i call my doctor? I have felt nauseated today

Answer

Penicillin antibiotics can reduce the clearance of methotrexate from your body, potentially leading to increased concentrations of methotrexate. Increased concentrations of methotrexate can lead to increased side effects of methotrexate. Common side effects of methotrexate include but are not limited to:

  • Diarrhea
  • Nausea
  • Photosensitivity
  • Dizziness
  • Headache
  • Rash

The severity of the drug interaction may depend on the timing between the doses of methotrexate and penicillin. Methotrexate is generally cleared from the body in 10 to 12 hours after a single dose.

As is common with dosing for ectopic pregnancy; if methotrexate treatment was one to two doses and was dosed many days earlier than penicillin was given, then an interaction may not be responsible for the side effects. The reaction may have just been due to the penicillin itself as common adverse reactions to penicillin include but are not limited to:

  • Diarrhea
  • Rash
  • Anemia
  • Nausea
  • Vomiting
  • Fever

If you have completed therapy with methotrexate, the side effects from the interaction should not continue while using penicillin as the methotrexate will be cleared from the body in a day or two.

If you however will be continuing on methotrexate and penicillin, be sure to reach out to your doctor as the side effects may continue.

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