Drug Interaction Report

Mesalamine and Phenytoin: Interaction Details

A pharmacist-reviewed analysis of the Mesalamine and Phenytoin 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

Phenytoin

Dilantin Phenytek
+

Mesalamine

Apriso Apriso® Asacol HD® Asacol® Canasa Delzicol Delzicol® Lialda
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 115 documented Mesalamine interactions, 86 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

Increased phenytoin or fosphenytoin (prodrug of phenytoin) exposure and an increased risk of phenytoin or fosphenytoin toxicity

Interaction Deep Dive

Concurrent administration of phenytoin or fosphenytoin (prodrug of phenytoin) and salicylates have resulted in increased exposure of phenytoin or fosphenytoin and lead to toxicity. Monitor patients for signs of phenytoin or fosphenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor) when receiving salicylate concurrently. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when salicylate is added to or withdrawn from a patient's regimen. Monitor phenytoin or fosphenytoin serum drug level during concurrent use of salicylate and phenytoin or fosphenytoin123.

Why it happens (mechanism)

Unknown

Common questions

Can I take Mesalamine and Phenytoin together?

Increased phenytoin or fosphenytoin (prodrug of phenytoin) exposure and an increased risk of phenytoin or fosphenytoin toxicity Always confirm with your pharmacist or prescriber before making any change.

How serious is the Mesalamine and Phenytoin 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.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Mesalamine or Phenytoin 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: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
  2. Product Information: PHENYTOIN SODIUM intravenous and intramuscular injection, phenytoin sodium intravenous and intramuscular injection. Acella Pharmaceuticals, LLC (per Dailymed), Alpharetta, GA, 2024. DailyMed
  3. Product Information: PHENYTOIN SODIUM oral extended-release capsules, phenytoin sodium oral extended-release capsules. Sun Pharmaceutical Industries, Inc. (per Dailymed), Cranbury, NJ, 2023. DailyMed
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Phenytoin

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All Phenytoin interactions (237)
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Mesalamine

Keep reading about Mesalamine

All Mesalamine interactions (115) Mesalamine drug information
Also serious with: Probenecid Aceclofenac Methotrexate Injection Diclofenac Ophthalmic
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:

Phenytoin + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Kava L-tryptophan Siberian Cocklebur St. John's Wort + 216 more
Mesalamine + Activated Charcoal Coffee Charcoal European Mandrake Glucomannan Guar Gum Gum Arabic Slippery Elm Tragacanth + 9 more

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.