Trusted by over 10K subscribers
    Free & discreet shipping on all prescriptions
    Affordable pricing with no hidden fees
    FDA-regulated pharmacies
    100% online process
    Trusted by over 10K subscribers
    Free & discreet shipping on all prescriptions
    Affordable pricing with no hidden fees
    FDA-regulated pharmacies
    100% online process
    Trusted by over 10K subscribers
    Free & discreet shipping on all prescriptions
    Affordable pricing with no hidden fees
    FDA-regulated pharmacies
    100% online process
    HomeMedication GuideDrug InteractionsMethotrexate + Ondansetron
    Minor interaction

    Does Methotrexate Interact With Ondansetron?

    In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase systemic concentrations of high-dose methotrexate.

    Reviewed by the OmniRx Health clinical teamLast reviewed Jul 4, 2026

    Severity: Minor

    Severity basis: drug interactions section. Combining Methotrexate (Antimetabolite DMARD) and Ondansetron (5-HT3 antiemetic) is classified as a minor interaction.

    What to Do

    This is generally a minor interaction, but review it with your pharmacist to be sure it is safe for you.

    How This Interaction Works

    Interactions like this one can happen when two medicines have overlapping effects, or when one changes how the other is absorbed, broken down, or cleared from the body. Methotrexate is a antimetabolite dmard and Ondansetron is a 5-ht3 antiemetic; together they are documented as a minor interaction. How much this matters depends on your dose, your other medications, and your overall health.

    If You Take Both Medications

    If you have been prescribed both Methotrexate and Ondansetron, do not start, stop, or change either medication on your own — some medicines are unsafe to stop suddenly. Tell your prescriber and pharmacist that you take both so they can decide whether the combination is right for you, adjust the dose, monitor you more closely, or suggest an alternative.

    From the FDA Label

    In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase systemic concentrations of high-dose methotrexate.

    Source: FDA structured product labeling (set_id 00327696-c496-4c83-a63e-9e29fd6246d4).

    Methotrexate

    Antimetabolite DMARD

    Brands: Trexall, Otrexup, Rasuvo

    View Methotrexate safety profile

    Ondansetron

    5-HT3 antiemetic

    Brands: Zofran

    View Ondansetron safety profile

    Check these against your full medication list in our free Interaction Checker

    Frequently Asked Questions

    Can you take Methotrexate and Ondansetron together?

    Methotrexate and Ondansetron have a documented minor interaction. This is generally a minor interaction, but review it with your pharmacist to be sure it is safe for you.

    How serious is the Methotrexate and Ondansetron interaction?

    It is classified as a minor interaction, based on the FDA label's drug interactions section. A minor interaction is usually limited in effect but is still worth discussing with your care team.

    What should I do if I'm taking both Methotrexate and Ondansetron?

    If you have been prescribed both Methotrexate and Ondansetron, do not start, stop, or change either medication on your own — some medicines are unsafe to stop suddenly. Tell your prescriber and pharmacist that you take both so they can decide whether the combination is right for you, adjust the dose, monitor you more closely, or suggest an alternative.

    This information is educational — not medical advice.

    This page is provided for general educational purposes and summarizes publicly available data from sources such as the U.S. Food & Drug Administration. It is not a substitute for the judgment of a licensed clinician and should not be used to start, stop, or change any medication. It may be incomplete or out of date, and individual circumstances vary. Always talk with your prescriber or pharmacist about your specific medications and health conditions. If you think you may have a medical emergency, call 911.

    Questions About Your Medications?

    A licensed OmniRx provider can review your full medication list and help you understand what's safe for you — no office visit required.