Phenobarbital and Cenobamate Interaction
Drug interaction information between Phenobarbital and Cenobamate.
Phenobarbital and Cenobamate have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Phenobarbital and Cenobamate. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Cenobamate causes the levels of phenobarbital in your blood to go up. This makes it more likely that you will have a bad reaction to the phenobarbital.
What To Do
Your doctor may need to lower your dose of phenobarbital to keep you safe while you take cenobamate.
FDA Label Information
( 7.1 ) Phenobarbital and Clobazam: Reduce dosage as needed when used concomitantly with XCOPRI. phenobarbital ↑ plasma concentrations Because of a potential for an increase in the risk of adverse reactions from these drugs, consider a reduction in dosage of phenobarbital or clobazam, as clinically appropriate, when used concomitantly with XCOPRI.
Phenobarbital Also Interacts With
- Nirmatrelvir/Ritonavir major
- Ranolazine major
- Voriconazole major
- Canagliflozin moderate
- Clarithromycin moderate
Cenobamate Also Interacts With
- Clobazam moderate
- Lamotrigine minor
- Carbamazepine minor
- Phenytoin minor
Frequently Asked Questions
Can I take Phenobarbital and Cenobamate together?
This is a moderate interaction. Your doctor may need to lower your dose of phenobarbital to keep you safe while you take cenobamate.
How serious is the interaction between Phenobarbital and Cenobamate?
This interaction is classified as "moderate" severity by the FDA. Moderate interactions may worsen your condition or change how your medications work.
Why do Phenobarbital and Cenobamate interact?
Cenobamate causes the levels of phenobarbital in your blood to go up. This makes it more likely that you will have a bad reaction to the phenobarbital.
Understanding the Phenobarbital and Cenobamate Interaction
FDA-approved prescribing information for these two drugs flags their combination as a moderate-severity interaction. Phenobarbital belongs to the Anticonvulsant (Barbiturate) class and Cenobamate belongs to the Anticonvulsant class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Cenobamate causes the levels of phenobarbital in your blood to go up. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Phenobarbital has 59 total documented interactions on file in this dataset, and Cenobamate has 5. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Your doctor may need to lower your dose of phenobarbital to keep you safe while you take cenobamate. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Phenobarbital or Cenobamate based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.