Phenytoin and Cisplatin Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Cisplatin Injection
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.
What happens
Reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure
Interaction Deep Dive
Concurrent administration of phenytoin or fosphenytoin (prodrug of phenytoin) and CISplatin have resulted in reduced phenytoin or fosphenytoin exposure. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when CISplatin is added to or withdrawn from a patient's regimen123. Combined therapy with CISplatin, vinBLAStine, and bleomycin was reported to result in decreased levels of phenytoin and increased seizure activity in a 24-year-old woman 4.
Why it happens (mechanism)
Increased metabolism of phenytoin
Literature reports
2 reports — tap to read
a) Combined therapy with CISplatin, vinBLAStine, and bleomycin was reported to result in decreased levels of phenytoin and increased seizure activity in a 24-year-old woman 4. And in a 36-year-old woman with epilepsy experienced tonic-clonic seizures during antineoplastic therapy with CISplatin and DOXOrubicin to treat adenocarcinoma. Two days after onset of therapy, plasma concentrations of anticonvulsant medications were reduced significantly: carBAMazepine 0.5 mg/L, phenytoin 0.3 mg/L, and valproic acid 24.3 mg/L. The following month, after increasing dosages of phenytoin and carBAMazepine, the patient again experienced tonic-clonic seizures during chemotherapy and was found to have subtherapeutic plasma levels of anticonvulsant medication: carBAMazepine 3.5 mg/L, phenytoin 0.2 mg/L, and valproic acid 34.1 mg/L. After again increasing the patient's anticonvulsant medication dosages, her final course of chemotherapy resulted in no seizure activity, in spite of the fact that her carBAMazepine levels remained low (1.4 mg/L). This indicates the need to increase anticonvulsant medication dosages when combined with antineoplastic therapy 5.
b) In a study conducted at Johns Hopkins Oncology Center, 10 of 17 patients on phenytoin received 3 or more cycles of chemotherapy consisting of CISplatin and carmustine (BCNU). All 10 patients required increases in their daily phenytoin dosages to maintain therapeutic phenytoin levels. In addition, 4 of 7 patients on phenytoin who received fewer than 3 cycles of chemotherapy also required an increase in their oral phenytoin dosage. As a result, it was concluded that 74% of the patients on phenytoin required dosage increases during chemotherapy with cisplatin and BCNU. The variations in phenytoin levels were only observed in treatment cycles that contained CISplatin. None of the patients on phenytoin who received only BCNU chemotherapy were noted to have changes in their phenytoin plasma levels 6.
Common questions
Can I take Phenytoin and Cisplatin Injection together?
Reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenytoin and Cisplatin Injection 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 Phenytoin or Cisplatin Injection 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)
- Product Information: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM intravenous and intramuscular injection, phenytoin sodium intravenous and intramuscular injection. Acella Pharmaceuticals, LLC (per Dailymed), Alpharetta, GA, 2024. DailyMed
- Product Information: PHENYTOIN SODIUM oral extended-release capsules, phenytoin sodium oral extended-release capsules. Sun Pharmaceutical Industries, Inc. (per Dailymed), Cranbury, NJ, 2023. DailyMed
- Sylvester RK, Lewis FB, Caldwell KC, et al: Impaired phenytoin bioavailability secondary to cisplatinum, vinblastine, and bleomycin. Ther Drug Monit 1984; 6:302-305. PubMed
- Neef C & de Voogd-van der Straaten I: An interaction between cytostatic and anticonvulsant drugs. Clin Pharmacol Ther 1988; 43:372-375. PubMed
- Grossman SA, Sheidler VR, & Gilbert MR: Decreased phenytoin levels in patients receiving chemotherapy. Am J Med 1989; 87:505-510. DOI
Keep reading about Phenytoin
Keep reading about Cisplatin Injection
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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