Busulfan Injection and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Busulfan 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
Decreased plasma concentrations of busulfan
Interaction Deep Dive
Concurrent administration of busulfan and phenytoin has resulted in decreased plasma concentrations of busulfan by 15% or more, possibly due to induction of glutathione-S-transferase1. Decreased concentrations of both cyclophosphamide and busulfan may occur with concomitant use of cyclophosphamide and busulfan with phenytoin pretreatment 2.
Why it happens (mechanism)
Induction of busulfan metabolism by phenytoin
Literature reports
1 report — tap to read
a) Nine patients were treated with phenytoin and 8 patients were treated with diazepam as prophylactic anticonvulsant therapy during high-dose therapy with busulfan. A continuous decrease in the steady state level of busulfan has been reported in patients receiving phenytoin during the 4 days of therapy and increases in the clearance rate (from 2.80 +/-0.78 mL/min/kg for the first dose compared with 3.32 +/-0.99 mL/min/kg for the last dose). Also, a shorter busulfan elimination half-life was reported after the last dose (3.03 +/- 0.57 hours) compared to the first dose (3.94 +/- 1.1 hours). None of these changes were seen in the patients who were treated with diazepam. This suggests that anticonvulsants with less enzyme-inducing capabilities than phenytoin should be used in patients being treated with busulfan therapy 1.
Common questions
Can I take Busulfan Injection and Phenytoin together?
Decreased plasma concentrations of busulfan Always confirm with your pharmacist or prescriber before making any change.
How serious is the Busulfan Injection and Phenytoin interaction?
It is rated moderate. Can be significant — usually manageable with 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 Busulfan Injection 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 anything you'd monitor while I'm on both?
References (2)
Keep reading about Phenytoin
Keep reading about Busulfan Injection
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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