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    HomeMedication GuideDrug InteractionsHydrocodone Acetaminophen + Phenytoin
    Moderate interaction

    Does Hydrocodone Acetaminophen Interact With Phenytoin?

    Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in hydrocodone bitartrate and acetaminophen tablets-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions.

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

    Severity: Moderate

    Severity basis: warnings section (keywords: may increase). Combining Hydrocodone Acetaminophen (Opioid analgesic combination) and Phenytoin (Anticonvulsant) is classified as a moderate interaction.

    What to Do

    Use this combination with caution. Your prescriber may monitor you more closely or adjust doses.

    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. Hydrocodone Acetaminophen is a opioid analgesic combination and Phenytoin is a anticonvulsant; together they are documented as a moderate 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 Hydrocodone Acetaminophen and Phenytoin, 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

    Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in hydrocodone bitartrate and acetaminophen tablets-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions.

    Source: FDA structured product labeling (set_id ee248dfd-7aa7-7dcc-e053-2995a90af19f).

    Hydrocodone Acetaminophen

    Opioid analgesic combination

    Brands: Norco, Vicodin, Lortab

    View Hydrocodone Acetaminophen safety profile

    Phenytoin

    Anticonvulsant

    Brands: Dilantin

    View Phenytoin safety profile

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

    Frequently Asked Questions

    Can you take Hydrocodone Acetaminophen and Phenytoin together?

    Hydrocodone Acetaminophen and Phenytoin have a documented moderate interaction. Use this combination with caution. Your prescriber may monitor you more closely or adjust doses.

    How serious is the Hydrocodone Acetaminophen and Phenytoin interaction?

    It is classified as a moderate interaction, based on the FDA label's warnings section (keywords: may increase). A moderate interaction can be clinically meaningful and usually calls for monitoring or a dose adjustment.

    What should I do if I'm taking both Hydrocodone Acetaminophen and Phenytoin?

    If you have been prescribed both Hydrocodone Acetaminophen and Phenytoin, 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.

    Other Phenytoin Interactions