Omeprazole and Primidone: 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
Primidone
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.
Here's what's going on with these two medicines. Primidone (Mysoline) is partly turned into phenobarbital in your body, and phenobarbital speeds up how fast your body breaks down omeprazole (Prilosec). That means the omeprazole may not work as well, so heartburn or stomach acid problems could come back.
At the same time, omeprazole can slow the breakdown of phenobarbital, so the phenobarbital may build up. That could cause extra drowsiness, dizziness, or feeling unsteady. Please keep taking both exactly as prescribed. This is manageable. Let your pharmacist or doctor know you take both so they can watch you closely and fine-tune your doses if needed.
Bidirectional interaction. Primidone is metabolized in part to phenobarbital, a CYP2C19/CYP3A inducer. Directionally:
- Omeprazole (substrate): induced CYP2C19/CYP3A metabolism lowers omeprazole exposure and may reduce acid-suppression efficacy.
- Phenobarbital (CYP2C19 substrate): omeprazole inhibits CYP2C19, potentially raising phenobarbital exposure and sedation/toxicity risk.
Evidence is theoretical; onset unspecified; severity rated major. Management: if co-use is unavoidable, monitor omeprazole efficacy and consider dose increase (closely monitor neonates), and monitor for phenobarbital-related adverse effects with maintenance-dose titration guided by clinical response and levels.
What happens
Reduced omeprazole exposure, reduced efficacy of omeprazole, increased PHENobarbital exposure and an increased risk of PHENobarbital-related adverse effects
Interaction Deep Dive
When PHENobarbital (an inducer of CYP2C19/CYP3A) is taken together with omeprazole (a substrate of CYP2C19/CYP3A), omeprazole exposure can fall, potentially lowering how effective omeprazole is. Should such combined use be unavoidable, neonates should be watched closely and an increase in the omeprazole dose should be considered as appropriate. In the reverse direction, giving PHENobarbital (a CYP2C19 substrate) alongside omeprazole (a CYP2C19 inhibitor) may raise PHENobarbital exposure, thereby heightening the likelihood of adverse reactions related to PHENobarbital. Where this combination cannot be avoided, monitor closely for adverse reactions and consider adjusting the maintenance dosage of PHENobarbital 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
Good news: your care team can manage this. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
- Your team may monitor your acid-related symptoms (like heartburn) since omeprazole may work less well, and the omeprazole dose may need to be adjusted and individualized.
- They may also watch for phenobarbital side effects such as drowsiness, dizziness, or unsteadiness, and titrate that dose as needed.
- Tell your pharmacist and prescriber you take both.
Report new sedation or returning stomach symptoms to your care team.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Omeprazole and Primidone together?
Phenobarbital (from primidone) can weaken omeprazole, while omeprazole can raise phenobarbital levels and sedation risk; keep taking both and ask your care team to monitor and adjust your doses. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Primidone 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 Primidone interaction managed?
Good news: your care team can manage this. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your team may monitor your acid-related symptoms (like heartburn) since omeprazole may work less well, and the omeprazole dose may need to be adjusted and individualized. They may also watch for phenobarbital side effects such as drowsiness, dizziness, or unsteadiness, an… 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 Primidone 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 Primidone
Keep reading about Omeprazole
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