Drug & supplement interaction

Caffeine + Ethosuximide

Ethosuximide brand name: Zarontin.

Moderate Interaction
The bottom line Moderate

Caffeine has a moderate interaction with Ethosuximide. Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Caffeine and Ethosuximide

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ETHOSUXIMIDE (Zarontin)

Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

If you take ethosuximide (Zarontin) to keep absence seizures in check, here's the gist on caffeine. There's a theory that caffeine might work against ethosuximide a little, making the medicine less able to do its job. In plain terms, that could mean a higher chance of breakthrough seizures, like those brief staring or blinking spells coming back.

Now, the important part: this comes from animal studies using very high doses of caffeine, and it hasn't actually been seen in people. So your morning coffee or tea is very unlikely to cause a problem. I'd just avoid loading up on strong energy drinks or high-dose caffeine pills, and check with your pharmacist or doctor if you have concerns.

References
  1. Luszczki, J. J., Zuchora, M., Sawicka, K. M., Kozinska, J., and Czuczwar, S. J. Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures i

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Caffeine Also Interacts With Other Medications

Caffeine has 8 major, 482 moderate, 164 minor known drug interactions in our database — the Ethosuximide one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Caffeine

Covers the 2,830 medications we’ve checked against Caffeine. Pick one to open its full report.

From our Q&A

Questions About Caffeine or Ethosuximide

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Caffeine or Ethosuximide, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Ethosuximide

This page covers Caffeine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethosuximide page lists 226 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 9 major · 179 moderate · 38 minor.

From our pharmacist’s overview on the Ethosuximide page

“Ethosuximide (Zarontin) prevents absence seizures, and a steady blood level is what keeps them away, so I treat this list of 226 interacting supplements and herbs with real care, especially the nine rated major. More than half of the entries can change how the liver clears the drug; grapefruit can raise its level while St.”

Reviewed by 2 · Jul 18, 2026

Open the Ethosuximide interaction page

One more smart check

Taking Caffeine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 6,775 real supplement products containing Caffeine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Caffeine. Your product may carry other ingredients that interact with Ethosuximide too, on top of Caffeine — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Caffeine and Ethosuximide Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Caffeine
Top 5%

#24 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Ethosuximide
Steady interest

#2,267 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Caffeine

What is Caffeine?

  • Mental alertness and reducing fatigue
  • Improving athletic performance
  • Headache and migraine relief
  • Boosting focus and concentration
  • Weight loss aid

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too much can cause jitteriness, a racing heart, and sleep problems. Pregnant women and people with heart conditions or anxiety should be especially careful and check with a doctor or pharmacist.

Read the full Caffeine monograph & all interactions
Medication

About Ethosuximide

What Is Ethosuximide Used For?

Brand name: Zarontin

Ethosuximide — sold as Zarontin and also available as generic Ethosuximide — is used to control absence (petit mal) epilepsy. Absence seizures are brief episodes where a person loses awareness for a few seconds, often mistaken for daydreaming.

Both Zarontin and Ethosuximide products (capsule and oral solution forms) are approved for this use. Either may also be used alongside other seizure medicines when a patient has absence seizures together with other types of epilepsy.

See full Ethosuximide drug information
Keep checking

Other Drugs & Caffeine

Browse every other medication we’ve checked against Caffeine — both the ones with a known interaction and the ones without. Select any drug for the full detail.

8Major
482Moderate
164Minor
2,175No known interaction
Major

8 interactions

Moderate

482 interactions

Showing 60 of 482 moderate interactions — see all 482 on the Caffeine page.

Minor

164 interactions

Showing 60 of 164 minor interactions — see all 164 on the Caffeine page.

No interaction 2,175 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Pharmacist Counseling Corner

Taking Caffeine and Ethosuximide Together: Common Questions

Can you take Caffeine with Ethosuximide?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Caffeine and Ethosuximide interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Ethosuximide and Caffeine?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.