Carbamazepine with Primidone Interaction Details

Brand Names Associated with Carbamazepine

Brand Names Associated with Primidone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

Reduced carBAMazepine exposure, reduced efficacy of carBAMazepine, reduced PHENobarbital exposure and reduced efficacy of PHENobarbital

Interaction Summary

Concomitant use of carBAMazepine (a CYP3A4 substrate) and PHENobarbital (a CYP3A4 inducer) or primidone (metabolized to PHENobarbital) may decrease carBAMazepine exposure and possibly cause loss of efficacy. Additionally, decreased levels of primidone have been reported in patients taking carBAMazepine . Also, concomitant use of PHENobarbital (a CYP2C19 substrate) with carBAMazepine (a CYP2C19 inducer) may decrease PHENobarbital exposure, which may reduce the effectiveness of PHENobarbital. If concomitant use cannot be avoided, closely monitor for reduced efficacy (eg., breakthrough seizure) and consider titration of the PHENobarbital maintenance dosage accordingly .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Use caution with concomitant use of carBAMazepine and PHENobarbital or primidone, as coadministration may decrease carBAMazepine exposure and possibly cause loss of efficacy. Also, concomitant use of PHENobarbital (a CYP2C19 substrate) with carBAMazepine (a CYP2C19 inducer) may decrease PHENobarbital exposure, which may reduce the effectiveness of PHENobarbital. If concomitant use cannot be avoided, closely monitor for reduced efficacy (eg., breakthrough seizure) and consider titration of the PHENobarbital maintenance dosage accordingly .

Mechanism Of Interaction

Induction of hepatic enzyme-mediated metabolism of carBAMazepine by PHENobarbital; induction of CYP2C19-mediated metabolism of PHENobarbital

Literature Reports

A) Concomitant administration of primidone (metabolized to PHENobarbital) and carBAMazepine has been reported to result in lack of seizure control and low levels of carBAMazepine in a 15 year-old man 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) 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 .

C) A study was done on 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 .

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.

Primidone Overview

• Primidone is used alone or with other medications to control certain types of seizures. Primidone is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.