Doxorubicin and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Doxorubicin
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 DOXOrubicin exposure and reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure
Interaction Deep Dive
Avoid coadministration DOXOrubicin and phenytoin or fosphenytoin (prodrug of phenytoin)1. Concurrent use of DOXOrubicin and phenytoin or fosphenytoin may reduce exposure of both drugs 13. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when DOXOrubicin is added to or withdrawn from a patient's regimen 456. Although no formal drug interaction studies have been done with DOXOrubicin hydrochloride liposome injection, it may interact with drugs known to interact with the conventional formulation of DOXOrubicin 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of DOXOrubicin; induction of P-gp-mediated metabolism of DOXOrubicin; induction of phenytoin metabolism
Literature reports
1 report — tap to read
a) A 36-year-old woman with epilepsy requiring CISplatin and DOXOrubicin therapy for papillary adenocarcinoma experienced tonic-clonic seizures after 2 days of antineoplastic treatment. Plasma concentrations of carBAMazepine, valproic acid, and phenytoin were all determined to be subtherapeutic (0.5 mg/L, 24.3 mg/L, and 0.3 mg/L, respectively). One month later, she was controlled on phenytoin 450 mg daily, carBAMazepine 1200 mg daily, and valproic acid 1200 mg daily. During her second course of CISplatin and DOXOrubicin, she again suffered a tonic-clonic seizure. Plasma concentrations of her anticonvulsants were phenytoin 0.2 mg/L, carBAMazepine 3.5 mg/L, and valproic acid 34.1 mg/L. Three days following her chemotherapy, plasma concentrations of the anticonvulsants had returned to their previous values. Following the fourth and fifth course of treatment, the phenytoin was increased to 600 mg daily, and the patient experienced toxicity symptoms one week prior to her last chemotherapy course. Plasma phenytoin concentration at that time was 24.9 mg/L 7.
Common questions
Can I take Doxorubicin and Phenytoin together?
Reduced DOXOrubicin exposure and reduced phenytoin or fosphenytoin (prodrug of phenytoin) exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Doxorubicin 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 "delayed". Effects tend to build up gradually over days to weeks.
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 Doxorubicin 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 (7)
- Product Information: doxorubicin HCl intravenous injection, doxorubicin HCl intravenous injection. Pfizer Labs (per FDA), New York, NY, 2013.
- Product Information: DOXIL(R) intravenous injection, doxorubicin HCl liposome intravenous injection. Janssen Products, LP (per FDA), Horsham, PA, 2012. DailyMed
- Product Information: Dilantin-125(R) oral suspension, phenytoin oral suspension. Parke-Davis (per FDA), New York, NY, 2013. DailyMed
- 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
- Neef C & de Voogd-van der Straaten I: An interaction between cytostatic and anticonvulsant drugs. Clin Pharmacol Ther 1988; 43:372-375. PubMed
Keep reading about Phenytoin
Keep reading about Doxorubicin
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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