Ethosuximide Drug Interactions You Should Know About

If you're taking Ethosuximide for absence seizures, it's important to know which other medications, supplements, and substances can affect how it works. Drug interactions can make Ethosuximide less effective at controlling seizures—or increase your risk of side effects. This guide covers the most important interactions to be aware of.

How Drug Interactions Work

Ethosuximide is broken down (metabolized) in your liver, primarily by an enzyme called CYP3A4. Any medication that speeds up or slows down this enzyme can change how much Ethosuximide is in your blood:

• Enzyme inducers speed up the breakdown of Ethosuximide, which can lower its levels and make it less effective at controlling seizures.
• Enzyme inhibitors slow down the breakdown, which can raise Ethosuximide levels and increase the risk of side effects like nausea, drowsiness, and dizziness.

Other interactions involve additive effects—for example, combining Ethosuximide with other sedating medications can increase drowsiness beyond what either drug would cause alone.

Medications That Interact with Ethosuximide

Major Interactions

These interactions can significantly affect your seizure control or safety:

• Phenytoin (Dilantin) — An enzyme inducer that can lower Ethosuximide levels. At the same time, Ethosuximide may increase Phenytoin levels, raising the risk of Phenytoin toxicity. If you take both, your doctor will need to monitor blood levels of both drugs carefully.
• Carbamazepine (Tegretol) — A strong CYP3A4 inducer that can significantly reduce Ethosuximide levels, potentially leading to breakthrough seizures.
• Phenobarbital — Another enzyme inducer that can lower Ethosuximide blood levels.
• Isoniazid (INH) — Used to treat tuberculosis. Isoniazid may inhibit Ethosuximide metabolism, causing levels to rise and increasing the risk of side effects.
• Rifampicin (Rifadin) — A powerful enzyme inducer that increases Ethosuximide clearance, potentially reducing seizure control.
• CNS depressants — Opioid pain medications (Oxycodone, Hydrocodone, Morphine), benzodiazepines (Alprazolam/Xanax, Diazepam/Valium, Clonazepam/Klonopin), and alcohol can all increase drowsiness and sedation when combined with Ethosuximide.

Moderate Interactions

• Valproic Acid (Depakote, Depakene) — Often prescribed alongside Ethosuximide for epilepsy. Valproic Acid can have variable effects on Ethosuximide levels—sometimes increasing them, sometimes having no effect. Monitoring is recommended.
• Lamotrigine (Lamictal) — Ethosuximide may reduce Lamotrigine levels by up to 37% in children and 14% in adults. If you take both, your doctor may need to adjust your Lamotrigine dose.
• CYP3A4 inhibitors — Medications like Conivaptan, Ketoconazole, and certain HIV medications can slow Ethosuximide metabolism and raise its blood levels.
• Other CYP3A4 inducers — Medications like Efavirenz, Modafinil (Provigil), and certain herbal supplements can increase Ethosuximide breakdown.

Supplements and OTC Medications to Watch

Some over-the-counter products and supplements can also interact with Ethosuximide:

• St. John's Wort — A popular herbal supplement for depression that is a potent CYP3A4 inducer. It can significantly lower Ethosuximide levels and should be avoided.
• Antihistamines (Benadryl, Diphenhydramine) — Can increase drowsiness when combined with Ethosuximide. Use non-drowsy alternatives like Loratadine (Claritin) or Cetirizine (Zyrtec) when possible.
• Sleep aids (Melatonin, Doxylamine, ZzzQuil) — May increase sedation. Talk to your doctor before using any sleep aid with Ethosuximide.
• CBD products — CBD is a CYP3A4 inhibitor and may raise Ethosuximide levels. If you use CBD products, let your doctor know.

Food and Drink Interactions

The good news: Ethosuximide has no significant food interactions. It can be taken with or without food, and taking it with a meal may actually help reduce GI side effects like nausea.

However, there's one important drink to watch:

• Alcohol — Drinking alcohol while taking Ethosuximide can increase drowsiness, dizziness, and impaired coordination. It can also lower your seizure threshold, making seizures more likely. It's best to avoid alcohol or limit it significantly while on Ethosuximide.

What to Tell Your Doctor

Before starting Ethosuximide—or any time your medication list changes—make sure your doctor and pharmacist know about:

• All prescription medications you're taking, especially other seizure drugs, antibiotics (especially Isoniazid or Rifampicin), and pain medications
• Over-the-counter medications, including allergy medications, sleep aids, and pain relievers
• Herbal supplements and vitamins, especially St. John's Wort and CBD
• Alcohol use — Be honest about how much and how often you drink
• Any planned surgeries or procedures — Anesthesia can interact with Ethosuximide, and your surgical team needs to know you're taking it

It's a good idea to keep an updated medication list on your phone or in your wallet. This makes it easy to share with any healthcare provider, even in an emergency.

Final Thoughts

Ethosuximide has fewer drug interactions than many other seizure medications, but the interactions it does have are important to know about. Enzyme inducers like Carbamazepine and Phenytoin can reduce its effectiveness, while enzyme inhibitors and CNS depressants can increase side effects. Always keep your doctor and pharmacist informed about everything you're taking.

For more on how Ethosuximide works in your body, see: How Does Ethosuximide Work? And for side effect guidance, check out: Ethosuximide Side Effects.

Need help finding Ethosuximide at an affordable price? Medfinder can help you locate pharmacies with stock near you.