Omeprazole and Phenobarbital: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Phenobarbital
Omeprazole
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.
These two medicines can affect each other in two ways. Phenobarbital speeds up how your body breaks down omeprazole, so the omeprazole may not control stomach acid as well (you might notice more heartburn or reflux). At the same time, omeprazole can slow how your body clears phenobarbital, so the phenobarbital may build up a bit and cause more side effects like extra drowsiness or grogginess.
The good news is your care team can handle this. They may check how you're doing, watch for side effects, and adjust either dose if needed. Please don't change anything on your own. Just let your pharmacist or doctor know you take both.
Bidirectional interaction (theoretical evidence).
- On omeprazole: phenobarbital induces CYP2C19 and CYP3A, lowering omeprazole exposure (reduced AUC/Cmax) and potentially reducing acid-suppression efficacy.
- On phenobarbital: omeprazole inhibits CYP2C19, potentially increasing phenobarbital exposure and risk of dose-related adverse effects (sedation, ataxia, respiratory depression).
Direction: reduced omeprazole effect, increased phenobarbital effect. Onset: unspecified. Management: if co-use is unavoidable, monitor acid-suppression response and consider increasing omeprazole dose; monitor for phenobarbital toxicity and titrate its maintenance dose. Phenobarbital has a narrow therapeutic index, so small exposure changes matter. Closely monitor neonates.
What happens
Reduced omeprazole exposure, reduced efficacy of omeprazole, increased PHENobarbital exposure and an increased risk of PHENobarbital-related adverse effects
Interaction Deep Dive
Taking PHENobarbital (an inducer of CYP2C19/CYP3A) together with omeprazole (a substrate of CYP2C19/CYP3A) can lower omeprazole exposure, potentially diminishing the drug's effectiveness. When the combination is unavoidable, monitor neonates closely and think about raising the omeprazole dose as needed. In the reverse direction, giving PHENobarbital (a CYP2C19 substrate) alongside omeprazole (a CYP2C19 inhibitor) may raise PHENobarbital exposure, thereby heightening the potential for PHENobarbital-related adverse reactions. If the two cannot be separated, watch closely for adverse reactions and consider adjusting the PHENobarbital maintenance dose accordingly1.
Why it happens (mechanism)
Induction of CYP2C19-mediated metabolism of omeprazole; induction of CYP3A-mediated metabolism of omeprazole; inhibition of CYP2C19-mediated metabolism of PHENobarbital
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This interaction is manageable with monitoring and dose tailoring.
- Your team may increase the omeprazole dose if acid symptoms (heartburn, reflux) are not well controlled.
- They may watch for phenobarbital side effects (extra drowsiness, unsteadiness) and adjust the phenobarbital maintenance dose as needed.
- Neonates on these medicines are watched especially closely.
What to do: tell your pharmacist and prescriber you take both, report worsening reflux or new grogginess, and let them individualize your doses.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Omeprazole and Phenobarbital together?
Phenobarbital may weaken omeprazole's acid control while omeprazole may raise phenobarbital levels and side effects; keep taking both as prescribed and let your care team monitor and adjust the doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole 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 is the Omeprazole and Phenobarbital interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This interaction is manageable with monitoring and dose tailoring. Your team may increase the omeprazole dose if acid symptoms (heartburn, reflux) are not well controlled. They may watch for phenobarbital side effects (extra drowsiness, unsteadiness) and adjust the phenobarbital maintenance dose as needed. Neonates o… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Omeprazole 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 Omeprazole
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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