Drug interactions
Methotrexate + Sulfamethoxazole
Severity: Major
Methotrexate and Sulfamethoxazole: major interaction.
Last updated Sources: US FDA label, NCBI (US National Library of Medicine)
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
Co-trimoxazole with methotrexate has caused severe, sometimes fatal pancytopenia and megaloblastic anemia. Trimethoprim adds antifolate activity and sulfamethoxazole raises methotrexate exposure.
What this interaction means in plain words
Methotrexate and Sulfamethoxazole 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.
Why it happens
Additive inhibition of folate metabolism, plus reduced renal secretion and protein-binding displacement of methotrexate.
What to do
Avoid co-trimoxazole in patients on methotrexate and choose an alternative antibiotic. If unavoidable, monitor blood counts frequently.
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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References
- Bactrim / Bactrim DS (sulfamethoxazole and trimethoprim) tablets Prescribing Information - Drug Interactions: Methotrexate ("Avoid concurrent use"; protein-binding displacement and competition for renal transport raise free methotrexate) — FDA Label (DailyMed)
- Xatmep (methotrexate) oral solution Prescribing Information - 7 Drug Interactions (trimethoprim/sulfamethoxazole reported to increase bone marrow suppression with methotrexate) — FDA Label (DailyMed)
- Bourre-Tessier J, Haraoui B. Methotrexate drug interactions in the treatment of rheumatoid arthritis: a systematic review. J Rheumatol 2010;37:1416-21 (TMP-SMX: cytopenia risk in 1 observational study and 17 case reports) — PubMed
- Al-Quteimat OM, Al-Badaineh MA. Methotrexate and trimethoprim-sulphamethoxazole: extremely serious and life-threatening combination. J Clin Pharm Ther 2013;38:203-5 — PubMed
- Groenendal H, Rampen FH. Methotrexate and trimethoprim-sulphamethoxazole - a potentially hazardous combination (fatal pancytopenia). Clin Exp Dermatol 1990;15:358-60 — PubMed
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
Frequently asked questions
Can I take Methotrexate with Sulfamethoxazole?
MediHelp rates the interaction as major. Methotrexate and Sulfamethoxazole 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. Co-trimoxazole with methotrexate has caused severe, sometimes fatal pancytopenia and megaloblastic anemia. Trimethoprim adds antifolate activity and sulfamethoxazole raises methotrexate exposure.
How serious is the interaction between Methotrexate and Sulfamethoxazole?
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 co-trimoxazole in patients on methotrexate and choose an alternative antibiotic. If unavoidable, monitor blood counts frequently.
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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