Drug Interaction Report

Ciprofloxacin and Methotrexate: Interaction Details

A pharmacist-reviewed analysis of the Ciprofloxacin and Methotrexate interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Ciprofloxacin

No brand names on record
+

Methotrexate

Jylamvo Otrexup Rasuvo Reditrex Rheumatrex® Trexall Trexall® Xatmep
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 162 documented Ciprofloxacin interactions, 133 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased methotrexate exposure, an increased risk of methotrexate-related severe adverse reactions, reduced active metabolite formation, possibly reduced methotrexate efficacy and an increased risk of hepatotoxicity

Interaction Deep Dive

Exert caution when methotrexate is coadministered with ciprofloxacin (an oral antibiotic and also a hepatotoxic agent) as it may increase methotrexate exposure due to inhibition of renal tubular transport of methotrexate2, which may increase the risk of methotrexate severe adverse reactions 12. In some cases, the coadministration of methotrexate with ciprofloxacin may also subsequently reduce active metabolite formation, which may reduce the clinical effectiveness of methotrexate. If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions 1.

Why it happens (mechanism)

Inhibition of renal tubular transport of methotrexate by ciprofloxacin; additive hepatotoxicity

Common questions

Can I take Ciprofloxacin and Methotrexate together?

Increased methotrexate exposure, an increased risk of methotrexate-related severe adverse reactions, reduced active metabolite formation, possibly reduced methotrexate efficacy and an increased risk of hepatotoxicity Always confirm with your pharmacist or prescriber before making any change.

How serious is the Ciprofloxacin and Methotrexate interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Ciprofloxacin or Methotrexate need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (2)

  1. Product Information: JYLAMVO oral solution, methotrexate oral solution. Shorla Oncology Inc (per FDA), Cambridge, MA, 2024. DailyMed
  2. Product Information: CIPROFLOXACIN oral tablets, ciprofloxacin oral tablets. Solco Healthcare US, LLC (per Dailymed), Somerset, NJ, 2024. DailyMed
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Ciprofloxacin

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All Ciprofloxacin interactions (162)
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Methotrexate

Keep reading about Methotrexate

All Methotrexate interactions (420) Methotrexate drug information
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Ciprofloxacin + Activated Charcoal Apple Asarabacca Beer Grapefruit Siberian Cocklebur Sweet Orange Wine + 155 more
Methotrexate + Activated Charcoal Apple Beer Grapefruit Siberian Cocklebur Sweet Orange Wine African Wild Potato + 74 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.