Drug Interaction Report

Neomycin and Methotrexate Injection: Interaction Details

A pharmacist-reviewed analysis of the Neomycin and Methotrexate Injection 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

Methotrexate Injection

Abitrexate® Folex® Jylamvo Mexate® Otrexup Otrexup® Rasuvo Rasuvo®
+

Neomycin

No brand names on record
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 19 documented Neomycin interactions, 11 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
rapid
Evidence
theoretical
Severity
Major

What happens

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

Interaction Deep Dive

Coadministration of methotrexate with oral neomycin may increase methotrexate exposure, which may increase the risk of methotrexate severe adverse reactions. In some cases, the coadministration of methotrexate with oral neomycin 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 reactions1. When oral neomycin was taken with oral methotrexate, the AUC for methotrexate was reduced by 36 to 50%. Oral kanamycin has been reported to increase oral methotrexate absorption 23.

Why it happens (mechanism)

Reduced methotrexate absorption

Literature reports

1 report — tap to read

a) When oral neomycin was taken with oral methotrexate, the AUC for methotrexate was reduced by 36% to 50%. Oral kanamycin has been reported to increase oral methotrexate absorption 23.

Common questions

Can I take Neomycin and Methotrexate Injection together?

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

How serious is the Neomycin and Methotrexate Injection interaction?

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

How quickly could this interaction happen?

The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.

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 Neomycin or Methotrexate Injection 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 (3)

  1. Product Information: JYLAMVO oral solution, methotrexate oral solution. Shorla Oncology Inc (per FDA), Cambridge, MA, 2024. DailyMed
  2. Bleyer WA: The clinical pharmacology of methotrexate: new applications of an old drug. Cancer 1978; 41:36-51. PubMed
  3. Cohen MH, Creaven PJ, Fossieck, et al: Effect of oral prophylactic broad spectrum nonabsorbable antibiotics on the gastrointestinal absorption of nutrients and methotrexate in small cell bronchogenic carcinoma patients. Cancer 1976; 38:1556-1559. DOI
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Methotrexate Injection

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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:

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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.