Primidone and Felbamate: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Primidone
Felbamate
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
An increased risk of QT interval prolongation and an increased PHENobarbital exposure
Interaction Deep Dive
Avoid the concomitant use of PHENobarbital with other products with a known potential to prolong the QTc interval or products that may increase concentrations of PHENobarbital. PHENobarbital causes QTc interval prolongation. Concomitant use of PHENobarbital with felbamate may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation. If concomitant use of PHENobarbital with felbamate is unavoidable, monitor patients for increased risk of QTc interval prolongation1. PHENobarbital levels increased by 42% within five weeks after the addition of felbamate in one patient 2. In 12 healthy male volunteers ingesting PHENobarbital, the steady-state trough concentrations (Cmin) of PHENobarbital increased from 14.2 mcg/mL to 17.8 mcg/mL when felbamate 2400 mg daily was coadministered for one week. PHENobarbital was found to decrease felbamate concentrations by 29% 3.
Why it happens (mechanism)
Additive QT interval prolongation; decreased PHENobarbital metabolism
Literature reports
1 report — tap to read
a) PHENobarbital levels increased by 42% within five weeks after the addition of felbamate in one patient. This occurred despite the fact that the PHENobarbital dose was reduced when felbamate was added. The patient exhibited orthostatic hypotension and spasticity in the lower extremities, and could not be evaluated for coordination and gait. The PHENobarbital dose was held for three days and restarted at 75% of the previous dose. Neurologic symptoms were markedly improved at discharge 2.
Common questions
Can I take Primidone and Felbamate together?
An increased risk of QT interval prolongation and an increased PHENobarbital exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Primidone and Felbamate 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Primidone or Felbamate 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 (3)
- Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022. DailyMed
- Gidal BE & Zupanc ML: Potential pharmacokinetic interaction between felbamate and phenobarbital. Ann Pharmacother 1994; 28:455-458. PubMed
- Product Information: Felbatol(R), felbamate. Wallace Laboratories, Cranbury, NJ, 2000. DailyMed
Keep reading about Primidone
Keep reading about Felbamate
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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