Drug Interaction Report

Methotrexate Injection and Nitrous Oxide: Interaction Details

Name: Methotrexate Injection and Nitrous Oxide Interaction
Creator: Dr. Brian Staiger, PharmD, BCPS

A pharmacist-reviewed analysis of the Methotrexate Injection and Nitrous Oxide 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

Nitrous Oxide

No brand names on record

Methotrexate Injection

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

Medically reviewed by

Dr. Brian Staiger, PharmD, BCPS

Updated Aug 8, 2026

Editorial policy · Data sources

Interaction severity

Major

Potentially serious — often needs a change or close monitoring.

Minor

Moderate

Major

Contraindicated

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 354 documented Methotrexate Injection interactions, 332 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

An increased risk of methotrexate toxicity

Interaction Deep Dive

Avoid concomitant use of nitrous oxide anesthesia and methotrexate due to the potentiation of the effect of methotrexate on folate-dependent metabolic pathways by nitrous oxide, resulting in an increased risk of toxicity²¹. Consider alternative therapies in patients who have received prior nitrous oxide anesthesia ¹.

Why it happens (mechanism)

Reduced methotrexate absorption; potentiation of methotrexate on folate-dependent metabolic pathways by nitrous oxide

Common questions

Can I take Methotrexate Injection and Nitrous Oxide together?

An increased risk of methotrexate toxicity Always confirm with your pharmacist or prescriber before making any change.

How serious is the Methotrexate Injection and Nitrous Oxide 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 Methotrexate Injection or Nitrous Oxide 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)

Product Information: JYLAMVO oral solution, methotrexate oral solution. Shorla Oncology Inc (per FDA), Cambridge, MA, 2024. DailyMed
Product Information: XATMEP(R) oral solution, methotrexate oral solution. Silvergate Pharmaceuticals, Inc. (per FDA), Greenwood Village, CO, 2018. DailyMed

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Nitrous Oxide

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All Nitrous Oxide interactions (22)

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Methotrexate Injection

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About our interaction database: depth, not breadth

HelloPharmacist doesn't license one of the big commercial interaction databases, so what you'll find here is not a complete list of every known drug interaction. Instead, each entry is researched, analyzed, and written up individually — documented from the published literature, reviewed by a pharmacist, and cited so you can check every source yourself.

If a combination isn't listed here, it means we haven't documented it yet — never that it's safe. For screening a full medication list, we recommend pairing this site with a comprehensive tool like the Drugs.com Interaction Checker and, most importantly, a review by your own pharmacist. For a deep, plain-English, fully sourced explanation of a specific documented interaction — that's exactly what we built this for.

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.