Clorazepate and Omeprazole: 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
Clorazepate
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 can pile up in your system. Clorazepate (Tranxene) is a calming medicine in the same family as diazepam (Valium). Omeprazole (Prilosec) is a common acid-reducing medicine. The problem is that omeprazole slows down the liver enzymes that break clorazepate down. When that happens, clorazepate can build up higher than expected.
That can make you very drowsy, dizzy, foggy, or unsteady on your feet, which can lead to falls. The good news is your care team can manage this easily by adjusting your dose, watching you more closely, or picking a different acid medicine. Please don't stop either one on your own. Just check in with your pharmacist or doctor.
Mechanism: Omeprazole inhibits CYP2C19 (and CYP3A4), the enzymes that metabolize clorazepate and its active metabolite desmethyldiazepam. Neither drug is a prodrug in a way that reverses this, so inhibition raises benzodiazepine exposure.
- Direction: Increased clorazepate/desmethyldiazepam AUC and Cmax, higher risk of toxicity.
- Onset: Delayed; evidence: probable; severity: major.
- Effect: Excess sedation, CNS depression, psychomotor impairment, fall risk.
Management: Monitor for sedation and consider dose individualization. For ICU stress ulcer prophylaxis, prefer agents not dependent on hepatic CYP metabolism (ranitidine, sucralfate, or pantoprazole).
What happens
An increased risk of clorazepate toxicity
Interaction Deep Dive
The metabolism of both omeprazole and clorazepate depends on the cytochrome isoenzymes CYP2C19 and CYP3A4. Omeprazole inhibits the metabolic breakdown of clorazepate as well as its metabolite desmethyldiazepam, an effect that may hold clinical significance. When omeprazole is given together with dipotassium clorazepate over a short period, it can produce a substantial buildup of clorazepate concentrations. For stress ulcer prophylaxis in intensive care patients, the preferred agents are those that do not undergo metabolism by cytochrome P450 enzymes. Ranitidine, sucralfate, and pantoprazole are not anticipated to produce any clinically meaningful interaction with medications acting on the hepatic cytochrome P450 system2.
Why it happens (mechanism)
Unknown
How to manage this interaction
This is manageable with your care team. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
- Your clorazepate dose may need to be adjusted and individualized by your care team.
- Your team may monitor you more closely for signs of over-sedation.
- In some settings a different acid-reducing option (for example pantoprazole, ranitidine, or sucralfate) may be chosen because it interacts less with these liver enzymes.
Tell your pharmacist or doctor if you feel unusually sleepy, dizzy, confused, or unsteady, and ask them whether your combination is the best choice for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A 60-year-old man with a background of essential hypertension, alcohol-related fatty liver without hepatic cirrhosis, and a chronic smoker's cough was admitted to hospital for alcohol detoxification treatment. Intravenous dipotassium clorazepate was started on the fifth day of his hospital stay. Within 29 hours the patient lost consciousness, and dipotassium clorazepate was stopped. He received a cumulative dose of 1500 mg of dipotassium clorazepate, along with intravenous omeprazole 80 mg/day for stress ulcer prevention, furosemide, thiamine, heparin, glucose, and electrolyte solutions. He remained drowsy and comatose for several days. The serum level of desmethyldiazepam, the principal active metabolite of dipotassium clorazepate, measured 2100 mcg/L (therapeutic range 200-1000 mcg/L) seven days after dipotassium clorazepate was withdrawn. The half-life of desmethyldiazepam may vary from 30 to 200 hours. In this instance the half-life was estimated at roughly 550 hours. The patient began to improve thirteen days after dipotassium clorazepate was stopped. Clorazepate, similar to omeprazole, undergoes metabolism through the cytochrome P450 2C19 and 3A4 isoenzymes. Giving these two drugs together can lead to a significant buildup of clorazepate concentrations. In this case, the prolonged half-life of desmethyldiazepam is most likely attributable to an interaction between omeprazole and dipotassium clorazepate. Nonetheless, the high dose of dipotassium clorazepate, together with diminished metabolic capacity due to alcohol-related liver damage, may also have played a role 1.
Common questions
Can I take Clorazepate and Omeprazole together?
Omeprazole can raise clorazepate levels and cause excess sedation, so let your pharmacist or doctor tailor the dose or consider a different acid medicine, and don't stop either drug on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clorazepate and Omeprazole 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 Clorazepate and Omeprazole interaction managed?
This is manageable with your care team. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your clorazepate dose may need to be adjusted and individualized by your care team. Your team may monitor you more closely for signs of over-sedation. In some settings a different acid-reducing option (for example pantoprazole, ranitidine, or sucralfate) may be chosen becaus… 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 Clorazepate or Omeprazole 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 (2)
- Konrad A: Protracted episode of reduced consciousness foloowing co-medication with omeprazole and clorazepate. Clin Drug Invest 2000; 19:307-311.
- Konrad A: Protracted episode of reduced consciousness following co-medication with omeprazole and clorazepate. Clin Drug Invest 2000; 19:307-311. DOI
Keep reading about Clorazepate
Keep reading about Omeprazole
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