Carbamazepine with Pentobarbital Interaction Details
Brand Names Associated with Carbamazepine
- Carbamazepine
- Carbatrol®
- Epitol®
- Equetro®
- Tegretol®
- Tegretol®-XR
- Teril®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 25, 2023
Interaction Effect
Decreased carbamazepine effectiveness with loss of seizure control
Interaction Summary
Concomitant use of carbamazepine and primidone (a prodrug of phenobarbital) has been suggested to lower the primidone concentration/dose ratio, while increasing the phenobarbital concentration to primidone concentration ratio. Concurrent therapy has also been reported to lower carbamazepine concentrations , with the barbiturate decreasing the level of carbamazepine while increasing the level of 10, 11-epoxide metabolite of carbamazepine . Evidence from these studies indicates that the metabolic effects may be more pronounced in children.
Severity
Moderate
Onset
Delayed
Evidence
Theoretical
How To Manage Interaction
With combined carbamazepine-pentobarbital therapy, monitor patients for seizure activity, especially pediatric patients, and adjust doses accordingly.
Mechanism Of Interaction
Microsomal enzyme induction with altered metabolism of either drug
Literature Reports
A) Concomitant administration of primidone and carbamazepine has been reported to result in lack of seizure control and low levels of carbamazepine in a 15 year-old male with partial complex seizures. Withdrawal of the primidone resulted in significant increases in carbamazepine serum levels with decreases in carbamazepine-10, 11-epoxide levels and a reduction (60%) in carbamazepine clearance .
B) A study of primidone levels and metabolism related to age and coadministration of other anticonvulsants found that children metabolize primidone more extensively than older persons and that coadministration of carbamazepine with primidone causes lower primidone to dose ratios and higher derived phenobarbital to primidone levels compared with primidone monotherapy .
C) Decreased levels of primidone, which is converted to phenobarbital and PEMA in vivo, have been reported in patients taking carbamazepine. A retrospective study statistically analyzed routine determinations of serum concentrations of anticonvulsant medications in patients on combination regimens. A phenobarbital-carbamazepine interaction was not specifically examined. A lowering of primidone levels during combination therapy with carbamazepine was found, but this difference was not statistically significant. It was unknown how long patients were on primidone therapy in each group before the levels were taken, so auto-induction of primidone could not be ruled out .
D) One study prospectively examined carbamazepine in patients already on other anticonvulsants. Eight patients were studied. Four patients were on phenytoin and phenobarbital, and four were on phenytoin, phenobarbital and primidone. Although the authors concluded that serum phenobarbital and primidone levels appeared to actually increase in some patients after nine days of carbamazepine therapy, numerical data were not given. The increased levels of phenobarbital and primidone could reflect only the incremental changes typical of rises to steady state levels .
E) One study examined 14 patients on concomitant carbamazepine and phenobarbital therapy. A mean decrease in carbamazepine levels was noted with an increase in levels of carbamazepine epoxide and free carbamazepine epoxide. The carbamazepine epoxide to carbamazepine ratio was also increased in these patients. No effect on phenobarbital or phenobarbital metabolite levels was observed . Similarly, a prospective, controlled study of carbamazepine reduction and discontinuation produced no change in phenobarbital levels in patients on concomitant therapy .
F) If phenytoin or carbamazepine (or any prodrugs) is used in pregnant women, there is a substantially increased risk of teratogenicity with many combinations of other anticonvulsants. The teratogenicity of these drugs is largely or wholly related to the levels of the reactive epoxide metabolites . The epoxide/parent drug ratio is generally increased when phenytoin or carbamazepine is combined with each other, any other drugs that induce cytochrome P450 enzymes (3A4, 2C9, 2C19) (barbiturates, felbamate), or drugs which inhibit epoxide hydrolase, such as valproic acid, progabide, and lamotrigine . Such combinations increase the risk of major birth defects 3- to 4-fold over monotherapy and about 10-fold over background rates.
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.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.