Cyclophosphamide and Phenobarbital: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenobarbital
Cyclophosphamide
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 cycloPHOSphamide exposure and a reduced efficacy of cycloPHOSphamide
Interaction Deep Dive
Concomitant use of PHENobarbital (a CYP2B6/CYP2C19 inducer) with cycloPHOSphamide (a CYP2B6/CYP2C19 substrate) may decrease cycloPHOSphamide exposure, which may reduce the efficacy of cycloPHOSphamide. If concomitant use cannot be avoided, closely monitor neonates and consider increasing the cycloPHOSphamide dosage accordingly1.
Why it happens (mechanism)
Induction of CYP2B6-mediated metabolism of cycloPHOSphamide; induction of CYP2C19-mediated metabolism of cycloPHOSphamide
Common questions
Can I take Cyclophosphamide and Phenobarbital together?
Reduced cycloPHOSphamide exposure and a reduced efficacy of cycloPHOSphamide Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclophosphamide and Phenobarbital interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Cyclophosphamide or Phenobarbital 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 (1)
- Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022. DailyMed
Keep reading about Phenobarbital
Keep reading about Cyclophosphamide
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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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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