Methotrexate and Probenecid: Drug Interaction Guide
Quick answer: This is a major interaction — avoid combining Methotrexate and Probenecid unless specifically directed by your doctor.
How Methotrexate interacts with Probenecid
Probenecid inhibits renal tubular organic anion transporters (OAT1/OAT3) that secrete methotrexate, prolonging its half-life and raising plasma levels by 3- to 4-fold, predisposing to severe toxicity.
What you should do
Avoid concomitant use; if unavoidable, reduce methotrexate dose substantially, ensure aggressive hydration and urinary alkalinisation, and monitor methotrexate levels closely.
Key facts
Severity
Major — avoid combination
Mechanism
Probenecid inhibits renal tubular organic anion transporters (OAT1/OAT3) that secrete methotrexate, prolonging its half-...
Action
Avoid concomitant use; if unavoidable, reduce methotrexate dose substantially, ensure aggressive hydration and urinary a...
Frequently asked questions
Can I take Methotrexate and Probenecid together?
No — this combination should generally be avoided. Avoid concomitant use; if unavoidable, reduce methotrexate dose substantially, ensure aggressive hydration and urinary alkalinisation, and monitor methotrexate levels closely.
What is the severity of this interaction?
The interaction between Methotrexate and Probenecid is classified as Major — avoid combination. Probenecid inhibits renal tubular organic anion transporters (OAT1/OAT3) that secrete methotrexate, prolonging its half-life and raising plasma levels by 3- to 4-fold, predisposing to severe toxicity.
What should I do if I'm prescribed both?
Avoid concomitant use; if unavoidable, reduce methotrexate dose substantially, ensure aggressive hydration and urinary alkalinisation, and monitor methotrexate levels closely. Always consult your prescribing clinician — do not stop or change medications without medical guidance.
Last reviewed: by iMedic Medical Editorial Team. Our editorial process.