Drug interactions
Methotrexate + Probenecid
Severity: Major
Methotrexate and Probenecid: major interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Probenecid reduces the renal elimination of methotrexate, leading to higher and more prolonged methotrexate concentrations. This can cause severe myelosuppression, mucositis and renal or hepatic toxicity, particularly at higher methotrexate doses.
What this interaction means in plain words
Methotrexate and Probenecid can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Methotrexate belongs to Oncology; Probenecid belongs to Genitourinary.
Why it happens
Probenecid inhibits organic anion transporters (OAT1/OAT3) in the renal tubule, blocking tubular secretion of methotrexate and its metabolites.
What to do
Avoid the combination where possible; if it is unavoidable, reduce the methotrexate dose and monitor blood counts, renal function and methotrexate levels closely.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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Other interactions of Methotrexate
- Acitretin + Methotrexate Contraindicated
- Adenovirus types 4 and 7 live + Methotrexate Contraindicated
- Influenza virus vaccine quadrivalent intranasal + Methotrexate Contraindicated
- Ketorolac + Methotrexate Contraindicated
- Measles mumps and rubella vaccine live + Methotrexate Contraindicated
- Measles mumps and rubella vaccine + Methotrexate Contraindicated
Other interactions of Probenecid
- Ketorolac intranasal + Probenecid Contraindicated
- Ketorolac + Probenecid Contraindicated
- Baricitinib + Probenecid Major
- Ceftazidime / avibactam + Probenecid Major
- Pralatrexate + Probenecid Major
- Probenecid + Roxadustat Major
Frequently asked questions
Can I take Methotrexate with Probenecid?
MediHelp rates the interaction as major. Methotrexate and Probenecid can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Probenecid reduces the renal elimination of methotrexate, leading to higher and more prolonged methotrexate concentrations. This can cause severe myelosuppression, mucositis and renal or hepatic toxicity, particularly at higher methotrexate doses.
How serious is the interaction between Methotrexate and Probenecid?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination where possible; if it is unavoidable, reduce the methotrexate dose and monitor blood counts, renal function and methotrexate levels closely.
What other medicines interact with Methotrexate?
MediHelp also lists interactions of Methotrexate with, for example, Acitretin, Adenovirus types 4 and 7 live, Influenza virus vaccine quadrivalent intranasal. The full list is on the Methotrexate page.
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