Carbamazepine with Midazolam Interaction Details
Brand Names Associated with Carbamazepine
- Carbamazepine
- Carbatrol®
- Epitol®
- Equetro®
- Tegretol®
- Tegretol®-XR
- Teril®
Brand Names Associated with Midazolam
- Midazolam
- Versed®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Decreased efficacy of midazolam
Interaction Summary
Use caution when coadministering carbamazepine (a CYP3A4 inducer) and midazolam (a CYP3A4 substrate) as this may result in decreased midazolam exposure. 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 . If used concomitantly monitor the patient and consider dosage adjustments .
Severity
Moderate
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Coadministration of carbamazepine (a CYP3A4 inducer) and midazolam (a CYP3A4 substrate) may result in decreased midazolam exposure and should be undertaken with caution. If used concomitantly monitor the patient and consider dosage adjustments.
Mechanism Of Interaction
Induction of CYP3A4-mediated midazolam metabolism by carbamazepine
Literature Reports
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 .
Carbamazepine Overview
-
Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.
Midazolam Overview
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Midazolam is given to children before medical procedures or before anesthesia for surgery to cause drowsiness, relieve anxiety, and prevent any memory of the event. Midazolam is in a class of medications called benzodiazepines. It works by slowing activity in the brain to allow relaxation and sleep.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.