Omeprazole and Diazepam: 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
Diazepam
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.
If you take Valium (diazepam) and Prilosec (omeprazole) together, here is what is going on. Your body uses a liver enzyme to break down diazepam. Omeprazole slows that enzyme down, so diazepam can build up and stick around longer than usual.
In plain terms, that means the calming, drowsy effects of diazepam may feel stronger and last longer. You might notice more sleepiness, dizziness, or trouble concentrating. The good news is this is very manageable. Your care team can lower your diazepam dose and keep an eye on how you feel. Please don't change anything on your own, just talk with your pharmacist or doctor.
Effect: Increased diazepam exposure via omeprazole inhibition of CYP2C19, the primary enzyme in diazepam metabolism. Result is reduced diazepam clearance, delayed elimination, and enhanced/prolonged benzodiazepine effect.
- Direction: Increased diazepam AUC and effect (neither drug is a prodrug here).
- Onset: Delayed. Evidence: Probable. Severity: Major.
- Note: Reduced clearance was seen mainly in CYP2C19 extensive metabolizers; minimal impact in poor metabolizers.
- Management: Monitor for excess sedation, psychomotor impairment, and respiratory depression; reduce diazepam dose as needed and individualize.
What happens
Increased diazepam exposure
Interaction Deep Dive
Taking omeprazole together with diazepam can raise diazepam exposure. Watch for heightened sedation in patients and lower the diazepam dose when necessary1. Reports indicate that using diazepam alongside omeprazole reduces the rate of diazepam metabolism and extends its elimination, which produces stronger and longer-lasting benzodiazepine effects 634. According to one study, reduced diazepam clearance was seen in nearly half of the patients classified as fast metabolizers of omeprazole, whereas in slow metabolizers of omeprazole the combination had minimal impact 2.
Why it happens (mechanism)
Inhibition of CYP2C19-mediated metabolism of diazepam
How to manage this interaction
This interaction is very manageable with your care team's help.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your diazepam dose may be lowered and individualized to account for the higher levels.
- Your team may monitor you more closely for increased sedation, drowsiness, dizziness, or feeling unsteady.
- Watch for extra sleepiness, especially early on, and avoid driving until you know how you feel.
Tell your pharmacist or doctor if you notice more drowsiness than usual, and ask before starting or stopping either medicine.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) Giving omeprazole 20 mg once daily together with intravenous diazepam 0.1 mg/kg produced a 27% reduction in clearance and a 36% rise in the diazepam half-life 1.
b) In a double blind, crossover study, adding omeprazole for patients receiving diazepam produced a 25% to 50% decrease in diazepam clearance. This interaction was seen in roughly 40% of patients who were fast metabolizers of omeprazole. Among slow metabolizers, the interaction had little significance 2.
c) Coadministration of diazepam and omeprazole led to a 130% rise in the mean elimination half-life of diazepam along with resulting increases in plasma diazepam concentrations 3.
d) Diazepam undergoes metabolism through the cytochrome P450 enzyme system. Omeprazole was reported to inhibit specific enzymes within the P450 system in studies combining omeprazole and diazepam in vitro and in vivo, in both animals and humans 4.
e) Human liver microsomes were employed to examine the conversion of diazepam into its two principal metabolites, nordiazepam (NDZ) and 3-hydroxydiazepam (3-HDZ). The inhibition of these two pathways by omeprazole and omeprazole sulphone was also examined. Omeprazole sulphone inhibited both pathways to a similar degree; however, the NDZ pathway was less prone to omeprazole inhibition 5.
Common questions
Can I take Omeprazole and Diazepam together?
Omeprazole can raise diazepam levels and make you more sedated, so your doctor may lower your diazepam dose and watch you more closely. Keep taking both as prescribed and report any extra drowsiness. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Diazepam 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 is the Omeprazole and Diazepam interaction managed?
This interaction is very manageable with your care team's help. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your diazepam dose may be lowered and individualized to account for the higher levels. Your team may monitor you more closely for increased sedation, drowsiness, dizziness, or feeling unsteady. Watch for extra sleepiness, especially early on, and avoid… Management is individual — always follow your own care team's guidance.
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 Omeprazole or Diazepam 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 (6)
- Product Information: KONVOMEP(TM) powder for oral suspension, omeprazole sodium bicarbonate powder for oral suspension. Azurity Pharmaceuticals Inc (per manufacturer), Woburn, MA, 2022. DailyMed
- Andersson T, Cederberg C, Edvardsson G, et al: Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. Clin Pharmacol Ther 1990; 47:79-85. PubMed
- Gugler R & Jensen JC: Omeprazole inhibits elimination of diazepam (letter). Lancet 1984; 1:969. DOI
- von Herrath D & Thimme W: Wechselwirkungen von omeprazole und cimetidine mit diazepam. Der Arzneimittelbrief 1993; 27:87.
- Zomorodi K & Houston JB: Diazepam-omeprazole inhibition interaction: an in vitro investigation using human liver microsomes. Br J Clin Pharmacol 1996; 2:157-162.
- Product Information: Prilosec(R), omeprazole. Astra Merck Inc. Wayne, PA, 1997. DailyMed
Keep reading about Diazepam
Keep reading about Omeprazole
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