Valproic Acid with Ethosuximide Interaction Details

Brand Names Associated with Valproic Acid

Brand Names Associated with Ethosuximide

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

An increased risk of ethosuximide toxicity

Interaction Summary

Valproate inhibits the metabolism of ethosuximide. Administration of a single ethosuximide 500 mg dose with valproate (800 to 1600 mg/day) to six healthy volunteers resulted in a 25% increase in elimination half-life of ethosuximide and a 15% decrease in valproate total clearance compared to ethosuximide alone. Monitor patients receiving valproate and ethosuximide concomitantly for alterations in serum concentrations of both drugs. Administration of ethosuximide in patients receiving valproic acid therapy was reported to result in significant increases in ethosuximide half-life (from 44 to 54 hours) and a significant decrease in total body clearance (11.2 to 9.5 mL/minute) .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Monitor patients receiving valproate and ethosuximide concomitantly for alterations in serum concentrations of both drugs.

Mechanism Of Interaction

Inhibition of ethosuximide metabolism

Literature Reports

A) Valproate inhibits the metabolism of ethosuximide. Administration of a single ethosuximide 500 mg dose with valproate (800 to 1600 mg/day) to six healthy volunteers resulted in a 25% increase in elimination half-life of ethosuximide and a 15% decrease in valproate total clearance compared to ethosuximide alone .

Valproic Acid Overview

• Valproic acid is used alone or with other medications to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). It is also used to prevent migraine headaches but not to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. It works by increasing the amount of a certain natural substance in the brain.

Ethosuximide Overview

• Ethosuximide is used to control absence seizures (petit mal) (a type of seizure in which there is a very short loss of awareness during which the person may stare straight ahead or blink his eyes and does not respond to others). Ethosuximide is in a class of medications called anticonvulsants. It works by reducing 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.