Does Fluoxetine Interact With Phenytoin?

Monoamine Oxidase Inhibitors (MAOIs): ( 2.9 , 2.10 , 4.1 , 5.2 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway ( 7.7 ) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued ( 5.2 , 7.7 ) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs ( 7.2 ) Benzodiazepines: Diazepam – increased t½, alprazolam - further psychomo…

Severity: Moderate

Severity basis: drug interactions section (keywords: monitor, caution). Combining Fluoxetine (SSRI antidepressant) 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.

From the FDA Label

Monoamine Oxidase Inhibitors (MAOIs): ( 2.9 , 2.10 , 4.1 , 5.2 ) Drugs Metabolized by CYP2D6: Fluoxetine is a potent inhibitor of CYP2D6 enzyme pathway ( 7.7 ) Tricyclic Antidepressants (TCAs): Monitor TCA levels during coadministration with fluoxetine or when fluoxetine has been recently discontinued ( 5.2 , 7.7 ) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs ( 7.2 ) Benzodiazepines: Diazepam – increased t½, alprazolam - further psychomo…

Source: FDA structured product labeling (set_id 02283de9-6087-45f7-a9ce-3b082ce860de).

Fluoxetine

SSRI antidepressant

Brands: Prozac, Sarafem

View Fluoxetine safety profile

Phenytoin

Anticonvulsant

Brands: Dilantin

View Phenytoin safety profile

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

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 It may be incomplete or out of date, and individual circumstances vary.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.