Methotrexate and Penicillin: Drug Interaction Guide
Quick answer: This is a major interaction — avoid combining Methotrexate and Penicillin unless specifically directed by your doctor.
How Methotrexate interacts with Penicillin
Penicillins compete with methotrexate for renal tubular secretion via organic anion transporters, reducing methotrexate clearance and elevating systemic exposure and toxicity.
What you should do
Avoid concurrent use during high-dose methotrexate therapy. For low-dose regimens, monitor methotrexate levels, full blood count and renal function.
Key facts
Severity
Major — avoid combination
Mechanism
Penicillins compete with methotrexate for renal tubular secretion via organic anion transporters, reducing methotrexate ...
Action
Avoid concurrent use during high-dose methotrexate therapy. For low-dose regimens, monitor methotrexate levels, full blo...
Frequently asked questions
Can I take Methotrexate and Penicillin together?
No — this combination should generally be avoided. Avoid concurrent use during high-dose methotrexate therapy. For low-dose regimens, monitor methotrexate levels, full blood count and renal function.
What is the severity of this interaction?
The interaction between Methotrexate and Penicillin is classified as Major — avoid combination. Penicillins compete with methotrexate for renal tubular secretion via organic anion transporters, reducing methotrexate clearance and elevating systemic exposure and toxicity.
What should I do if I'm prescribed both?
Avoid concurrent use during high-dose methotrexate therapy. For low-dose regimens, monitor methotrexate levels, full blood count and renal function. Always consult your prescribing clinician — do not stop or change medications without medical guidance.
Last reviewed: by iMedic Medical Editorial Team. Our editorial process.