Midazolam Injection and Carbamazepine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Carbamazepine
Midazolam Injection
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.
What happens
Reduced midazolam exposure and reduced efficacy of midazolam, an increased risk of respiratory depression, profound sedation, hypotension and syncope
Interaction Deep Dive
Exert caution when carBAMazepine (a CYP3A4 inducer) is coadministered with midazolam (CNS depressant and CYP3A4 substrate) because of its primary CNS effect, such as an increased risk of respiratory depression, profound sedation, hypotension, and syncope1. Concomitant use may also reduce midazolam exposure 23. In a small study, carBAMazepine was been shown to greatly reduce the bioavailability of a single oral dose of midazolam and patients failed to have a hypnotic response to midazolam 4. If used concomitantly monitor the patient and consider dosage adjustments 23.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of midazolam; additive CNS depression
Literature reports
1 report — tap to read
a) Six patients with epilepsy and 7 healthy control subjects were studied to determine the effects of carBAMazepine and phenytoin on an oral dose of midazolam. Epileptic patients had been receiving either carBAMazepine (dose range 700 mg to 900 mg daily), phenytoin (dose range 150 mg to 300 mg daily), or both drugs twice daily for at least 2 months. The control subjects were not receiving any enzyme-inducing agents. All study participants were administered a single oral dose of midazolam 15 mg. In the patient group, the mean AUC of midazolam was only 5.7% (0.60 mcg/min/mL vs. 10.5 mcg/min/mL) and the Cmax was 7.4% (5.2 ng/mL vs. 70.4 ng/mL) of the control values. In one patient, only traces of midazolam (less than 0.1 ng/mL) were detectable in the plasma. The elimination half-life of midazolam was reduced to 1.3 hours in the patient group compared to 3.1 hours in the controls. There was no difference in the time to Cmax (1 hour) between the two groups. As expected from the reduced serum concentrations of midazolam, the majority of the patient group did not report any sedation. All of the subjects from the control group experienced sedative effects which lasted from 2 to 4 hours. The low midazolam plasma concentrations, decreased elimination half-life, and lack of sedative effects are most likely the result of CYP induction by carBAMazepine and phenytoin, since midazolam is extensively metabolized by CYP3A enzymes during first-pass and elimination phases 4.
Common questions
Can I take Midazolam Injection and Carbamazepine together?
Reduced midazolam exposure and reduced efficacy of midazolam, an increased risk of respiratory depression, profound sedation, hypotension and syncope Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midazolam Injection and Carbamazepine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Midazolam Injection or Carbamazepine 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 (4)
- Product Information: CARBATROL(R) oral extended-release capsules, carbamazepine oral extended-release capsules. Takeda Pharmaceuticals America Inc (per FDA), Lexington, MA, 2023. DailyMed
- Product Information: Tegretol(R)-XR oral extended-release tablets, carbamazepine oral extended-release tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Product Information: Tegretol(R) oral chewable tablets, oral tablets, oral suspension, carbamazepine oral chewable tablets, oral tablets, oral suspension. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Backman JT, Olkkola KT, Ojala M, et al: Concentrations and effects of oral midazolam are greatly reduced in patients treated with carbamazepine or phenytoin. Epilepsia 1996; 37:253-257. PubMed
Keep reading about Carbamazepine
Keep reading about Midazolam Injection
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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