Drug Interaction Report

Carboplatin and Phenytoin: Interaction Details

A pharmacist-reviewed analysis of the Carboplatin 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
+

Carboplatin

Kyxata Paraplatin
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 30 documented Carboplatin interactions, 10 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
rapid
Evidence
probable
Severity
Major

What happens

Reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure

Interaction Deep Dive

The coadministration of CARBOplatin with phenytoin or fosphenytoin (prodrug of phenytoin) resulted in a substantial reduction in phenytoin or fosphenytoin exposure and recurrent seizures in a single patient4. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when CARBOplatin is added to or withdrawn from a patient's regimen 123. The seizures subsided and phenytoin exposure returned to normal following increases in phenytoin or fosphenytoin dose 4. In other case reports, the addition of antineoplastic drugs in patients maintained on phenytoin resulted in lower phenytoin concentrations 5.

Why it happens (mechanism)

Unknown

Literature reports

2 reports — tap to read

a) CARBOplatin was reported to cause a substantial decrease in serum phenytoin concentrations, resulting in recurrent seizures in a single patient. The seizures subsided and serum phenytoin concentrations returned to normal following increases in phenytoin dose 4.

b) In a case reports, the addition of antineoplastic drugs in patients maintained on phenytoin resulted in lower phenytoin concentrations. The decrease in phenytoin concentration is thought to be due to altered bioavailability, however increased phenytoin elimination has been reported with high dose methotrexate 56.

Common questions

Can I take Carboplatin and Phenytoin together?

Reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Carboplatin 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 "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Carboplatin 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 (6)

  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
  4. Dofferhoff ASM & Berendsen HH: Decreased phenytoin level after carboplatin treatment. Am J Med 1990; 89:247-248. PubMed
  5. Riva R, Albani F, & Baruzzi A: On the interaction between phenytoin and antineoplastic agents (letter). Ther Drug Monit 1985; 7:123-126. DOI
  6. Grossman SA, Sheidler VR, & Gilbert MR: Decreased phenytoin levels in patients receiving chemotherapy. Am J Med 1989; 87:505-510. DOI
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Phenytoin

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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
Carboplatin + Activated Charcoal Acerola Alpha-lipoic Acid Coenzyme Q10 Coffee Charcoal Dimethylsulfoxide (dmso) European Mandrake Glucomannan + 19 more

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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.