Omeprazole and Midazolam: 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
Midazolam
No brand names on recordOmeprazole
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. Your body uses a liver enzyme to break down midazolam, a benzodiazepine used for calming, sedation, or sleep. Omeprazole (Prilosec) can slow that enzyme down a bit. When that happens, midazolam can build up and hang around longer, so you might feel more drowsy, foggy, unsteady on your feet, or very sleepy.
The good news is this is expected based on how the drugs work rather than something proven to cause big problems, and it is very manageable. Please don't change anything on your own. Your care team can watch how you respond, adjust the dose, or pick a different calming medicine if needed. Just tell them if you feel unusually sleepy or off balance.
Mechanism: Omeprazole inhibits CYP-mediated (CYP3A4/CYP2C19) oxidative metabolism of midazolam, reducing clearance and increasing exposure. Neither agent is activated by this pathway, so the expected direction is enhanced and prolonged benzodiazepine effect.
- Direction: increased midazolam AUC and prolonged sedation/CNS depression.
- Onset: delayed.
- Evidence: theoretical, extrapolated from diazepam-omeprazole data (reduced clearance seen mainly in extensive/fast omeprazole metabolizers).
- Magnitude: not quantified for this pair.
Management: Monitor for sedation, lethargy, ataxia, and slurred speech; titrate midazolam dose accordingly. Consider a glucuronidated benzodiazepine (lorazepam, oxazepam, temazepam) as an alternative.
What happens
Benzodiazepine toxicity (CNS depression, ataxia, lethargy)
Interaction Deep Dive
When diazepam and omeprazole are taken together, reports indicate that diazepam metabolism is slowed and its elimination is delayed, which produces stronger and more sustained benzodiazepine effects423. In one study, reduced diazepam clearance was seen in nearly half of the patients who were rapid metabolizers of omeprazole, whereas the combination held little importance in those who were slow metabolizers of omeprazole1. Comparable effects would be anticipated with concurrent midazolam and omeprazole, even though this has not been documented so far. Because lorazepam, oxazepam, and temazepam are benzodiazepines cleared through glucuronidation instead of the cytochrome P450 enzyme system, they may serve as suitable alternatives for patients who require both omeprazole and a benzodiazepine.
Why it happens (mechanism)
Slowed benzodiazepine metabolism and clearance
How to manage this interaction
The takeaway: this combination can make midazolam's calming effect stronger and longer-lasting. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may watch you more closely for signs of too much sedation, such as heavy drowsiness, lethargy, unsteadiness, or slurred speech.
- Your midazolam dose may need to be adjusted and individualized by your team.
- Your team might consider a different benzodiazepine that is cleared differently (lorazepam, oxazepam, or temazepam) if that fits your needs.
What to do: tell your pharmacist or prescriber if you feel unusually sleepy or off balance, and don't stop or change either drug on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Omeprazole and Midazolam together?
Omeprazole may slow the breakdown of midazolam, making its sedative effects stronger and longer, so watch for extra drowsiness and let your care team adjust the dose or pick an alternative if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and Midazolam interaction?
It is rated moderate. Can be significant — usually manageable with 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 Midazolam interaction managed?
The takeaway: this combination can make midazolam's calming effect stronger and longer-lasting. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may watch you more closely for signs of too much sedation, such as heavy drowsiness, lethargy, unsteadiness, or slurred speech. Your midazolam dose may need to be adjusted and individualized by yo… 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 Midazolam 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 anything you'd monitor while I'm on both?
References (4)
- 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.
- Product Information: Prilosec(R), omeprazole. Astra Merck Inc. Wayne, PA, 1997. DailyMed
Keep reading about Midazolam
Keep reading about Omeprazole
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