Carbamazepine with Nefazodone Interaction Details
Brand Names Associated with Carbamazepine
- Carbamazepine
- Carbatrol®
- Epitol®
- Equetro®
- Tegretol®
- Tegretol®-XR
- Teril®
Brand Names Associated with Nefazodone
- Nefazodone
- Serzone®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Reduced plasma concentrations and efficacy of nefazodone and its active metabolite, and an increased risk of carbamazepine toxicity (ataxia, nystagmus, diplopia, headache, vomiting, apnea, seizures, coma)
Interaction Summary
Coadministration of nefazodone and carbamazepine is contraindicated. Concomitant use may significantly reduce plasma concentrations of nefazodone and its active metabolite, resulting in reduced therapeutic efficacy of nefazodone. In a study conducted on 12 healthy volunteers, the coadministration of nefazodone with carbamazepine at steady-state resulted in a reduction in the mean AUC of nefazodone and hydroxynefazodone by 93% and 94%, respectively. Additionally, a 23% increase in carbamazepine plasma levels and a 21% decrease in carbamazepine-10,11 epoxide levels were noted. These two findings suggest that nefazodone inhibits carbamazepine metabolism through the CYP3A4 system, and carbamazepine induces nefazodone metabolism through the same pathway . Two other cases of nefazodone-induced carbamazepine toxicity have been reported in the literature .
Severity
Contraindicated
Onset
Delayed
Evidence
Established
How To Manage Interaction
Concomitant use of carbamazepine and nefazodone is contraindicated due to reduced efficacy of nefazodone and its active metabolite. In addition, concomitant use may also result in increased toxicity of carbamazepine .
Mechanism Of Interaction
Induction of CYP3A4-mediated nefazodone metabolism; inhibition of CYP3A4-mediated carbamazepine metabolism
Literature Reports
A) Twelve healthy male volunteers participated in an open-label multiple-dose study to explore the potential for an interaction between carbamazepine and nefazodone. Each subject received nefazodone 200 mg twice daily from days 1 through 5. A four-day washout period followed. On days 10 to 12, carbamazepine 200 mg daily was given, and the dose was increased to 200 mg twice daily from days 14 to 39. From days 40 to 44, nefazodone 200 mg twice daily and carbamazepine 200 mg twice daily were coadministered. Carbamazepine mean steady-state area under the concentration-time curve (AUC) increased from 60.77 mcg/hr/mL to 74.98 mcg/hr/mL in the presence of nefazodone, while the AUC of the metabolite carbamazepine-10,11-epoxide decreased from 7.1 mcg/hr/mL to 5.71 mcg/hr/mL. The maximum concentration (Cmax) of carbamazepine increased from 5794 mg/L to 7133.2 mg/L and the Cmax for carbamazepine-10,11-epoxide decreased from 680.5 mg/L to 535.2 mg/L. Nefazodone mean steady-state AUC was decreased from 7326 ng/hr/mL to 542 ng/hr/mL in the presence of carbamazepine, although the clinical significance of carbamazepine induction on nefazodone metabolism has not yet been studied .
B) A 35-year-old female with bipolar disorder developed carbamazepine toxicity following the addition of nefazodone (100 to 150 mg twice daily) to an existing drug regimen of carbamazepine (1000 mg daily) and risperidone (3 mg to 6 mg daily). Prior to nefazodone therapy, her carbamazepine serum concentrations ranged from 7.0 mcg/mL to 8.3 mcg/mL. Fifteen days after her nefazodone dose was increased to 300 mg daily, she presented with lightheadedness and ataxia. The carbamazepine serum concentration was 10.8 mcg/mL .
C) In a second case, a 39-year-old female with bipolar disorder developed carbamazepine toxicity after nefazodone (100 to 150 mg twice daily) was added to an existing regimen of carbamazepine (1000 mg daily). During concomitant therapy, serum carbamazepine levels increased to 15.1 mcg/mL from a previous range of 5.2 mcg/mL to 6.2 mcg/mL with carbamazepine alone .
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.
Nefazodone Overview
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Nefazodone is used to treat depression. Nefazodone is in a class of medications called serotonin modulators. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.
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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.