Taking Pencillin-Family Antibiotics With Methotrexate

In our latest question and answer, the pharmacist discusses the use of penicillin antibiotics and methotrexate.

Taking Pencillin-Family Antibiotics With Methotrexate
Feb 20, 2019

Jeannie asked

My 4-year-old is on oral methotrexate. I understand you need to wait 12 hours after methotrexate before starting antibiotics. Her antibiotics are for 10 days (ear infection). Should I wait 12 hours after the last dose of antibiotics before starting her back on the methotrexate?

At a glance

  • Penicillin and related antibiotics (e.g. amoxicillin) can increase methotrexate concentrations by decreasing elimination from the kidneys. This increases the risk of side effects. Nevertheless, they are sometimes used together in certain situations.


Methotrexate Blister Pack

You are correct that there is a significant interaction between some antibiotics and methotrexate. However, not all antibiotics share this interaction.

The most well-known is with penicillin (and its derivatives).

Penicillins reduce the elimination of methotrexate in the kidney, increasing concentrations which in turn could increase the risk of methotrexate-related side effects.

The prescribing information for methotrexate states the following regarding the interaction:

  • Methotrexate and penicillin interaction. PubMed
  • Effect of penicillin on the renal tubular secretion of methotrexate in the monkey. PubMed

Ready for a more personal experience with your meds?