Phenytoin and Bleomycin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Bleomycin
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 bleomycin have resulted in reduced phenytoin or fosphenytoin exposure. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when bleomycin is added to or withdrawn from a patient's regimen123. In case reports, the addition of antineoplastic drugs (bleomycin, carmustine, methotrexate, vinBLAStine, vinCRIStine) in patients maintained on phenytoin resulted in lower phenytoin concentration. The decrease in phenytoin concentration is thought to be due to altered bioavailability 5. However, increased phenytoin elimination has been reported with high-dose methotrexate 6.
Why it happens (mechanism)
Unknown
Literature reports
2 reports — tap to read
a) Combined therapy with CISplatin, vinBLAStine, and bleomycin therapy was reported to result in decreased levels of phenytoin and seizure activity in a 24-year-old woman. Studies revealed that phenytoin absorption was reduced to approximately 32% (normal, 80%) with antineoplastic therapy; the authors speculate that phenytoin malabsorption occurred possibly due to disruption of absorption at the cellular level with the combination chemotherapy 4.
b) In case reports, the addition of antineoplastic drugs (bleomycin, carmustine, methotrexate, vinBLAStine, vinCRIStine) in patients maintained on phenytoin resulted in lower phenytoin concentration. The decrease in phenytoin concentration is thought to be due to altered bioavailability 5. However, increased phenytoin elimination has been reported with high-dose methotrexate 6.
Common questions
Can I take Phenytoin and Bleomycin 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 Bleomycin 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 Bleomycin 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
- Jarosinski PF, Moscow JA, Alexander MS, et al: Altered phenytoin clearance during intensive chemotherapy for acute lymphoblastic leukemia. J Pediatr 1988; 112:996-999. DOI
- Riva R, Albani F, & Baruzzi A: On the interaction between phenytoin and antineoplastic agents (letter). Ther Drug Monit 1985; 7:123-126. DOI
Keep reading about Phenytoin
Keep reading about Bleomycin
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