Diazepam Rectal and Phenytoin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenytoin
Diazepam Rectal
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
Altered phenytoin or fosphenytoin (prodrug of phenytoin) exposure
Interaction Deep Dive
Use caution with the concomitant administration of phenytoin or fosphenytoin (prodrug of phenytoin) and diazePAM, as phenytoin levels may be reduced1 or increased 2. Consider phenytoin or fosphenytoin dose adjustments to achieve optimal clinical response when diazePAM is added to or withdrawn from a patient's regimen 3451.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) Phenytoin toxicity occurred in a 44-year-old man who was given concomitant diazePAM therapy. The patient complained of headache, nystagmus, diplopia, and ataxia and was admitted to the hospital. Aside from his long-standing seizure disorder, his past medical history was unremarkable. His antiepileptic regimen of phenytoin, PHENobarbital, and lamoTRIgine had been unchanged for almost 5 months. Two weeks prior to admission his total phenytoin serum concentration was 8 mcg/mL. He was prescribed amoxicillin and diazePAM 2 days prior to his hospital admission. His serum phenytoin concentration was 37 mcg/mL in the hospital. DiazePAM and phenytoin were discontinued and the symptoms resolved 2.
Common questions
Can I take Diazepam Rectal and Phenytoin together?
Altered phenytoin or fosphenytoin (prodrug of phenytoin) exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam Rectal 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 "unspecified". The timing of this interaction is not well characterized.
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 Diazepam Rectal 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 (5)
- Product Information: Dilantin-125(R) oral suspension, phenytoin oral suspension. Parke-Davis (per FDA), New York, NY, 2014. DailyMed
- Murphy A & Wilbur K: Phenytoin-diazepam interaction. Ann of Pharmacother, 37(5), 659-663, 2003. PubMed
- 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
Keep reading about Phenytoin
Keep reading about Diazepam Rectal
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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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