Drug & supplement interaction

Kava + Fosphenytoin

Fosphenytoin brand name: Cerebyx.

Major Interaction
The bottom line Major

Fosphenytoin falls into 3 drug categories that Kava can interact with; the most serious is rated major. Combining kava with CNS depressants can have additive sedative effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions3
EvidenceA
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Fosphenytoin

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Kava interacts with whole categories of medication. Fosphenytoin falls into 3 of those categories, so it can interact with Kava in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

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Why this applies to Fosphenytoin

Fosphenytoin falls under CNS DEPRESSANTS — the group Kava interacts with.

Combining kava with CNS depressants can have additive sedative effects.
Kava has CNS depressant effects. Concomitant use of kava with other CNS depressants can increase the risk of drowsiness and motor reflex depression. Clinical practice guidelines from a joint taskforce of the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) recommend that CNS depressants, including alcohol and benzodiazepines, not be used with kava.
Severity Major Likelihood Probable Evidence A

Interaction 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..

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

Here's the thing to keep in mind with this pair: fosphenytoin (Cerebyx) is a seizure medicine that already slows down overactive electrical signals in the brain, and that comes with a calming, sedating side effect for many people. Kava works in a similar direction, gently quieting nerve activity. When you stack two calming agents like this, the drowsiness can add up.

So the realistic worry isn't a change in how your body breaks the drug down, it's extra sedation. You might feel unusually sleepy, foggy, dizzy, unsteady on your feet, or notice slower reflexes. Major anxiety guidelines actually advise against mixing kava with sedating medicines for this reason. Kava also carries a rare risk of liver harm. Please don't add or stop anything on your own. Talk with your doctor or pharmacist first.

References
  1. Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: systematic review and meta-analysis. J Clin Psychopharmacol 2000;20:84-9. PubMed
  2. Munte TF, Heinze HJ, Matzke M, Steitz J. Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task. Neuropsychobiology 1993;27:46-53.
  3. Cairney S, Maruff P, Clough AR, et al. Saccade and cognitive impairment associated with kava intoxication. Hum Psychopharmacol 2003;18:525-33. PubMed
  4. Sarris J, Kavanagh DJ, Byrne G, et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology 2009;205:399-407. PubMed
  5. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T
Moderate

HEPATOTOXIC DRUGS

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Fosphenytoin also falls under HEPATOTOXIC DRUGS.

Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.
Kava has been linked with over 100 cases of hepatotoxicity. Most cases occur with excessive and prolonged use. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs.
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

Here's the thing to keep in mind with kava and fosphenytoin (Cerebyx). This isn't about kava changing your seizure medicine's level in your blood. It's about your liver. Fosphenytoin, like its cousin phenytoin, can put a strain on the liver in some people, and kava has been tied to rare but real cases of liver injury, mostly with heavy or long-term use. Stacking two things that can stress the liver may add up.

I'll be honest, this concern is mostly theoretical and based on scattered case reports, not strong studies. Still, watch for warning signs like yellowing skin or eyes, dark urine, belly pain, or unusual tiredness. Please don't change anything on your own. Loop in your pharmacist or doctor first, since they may want to check your liver.

References
  1. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ 2001;322:139.
  2. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity [letter]. Ann Intern Med 2001;135:68-9.
  3. Liver Toxicity With Kava. Pharmacist's Letter/Prescriber's Letter. January 2001.
  4. Consultation letter MLX 286: Proposals to prohibit the herbal ingredient Kava-Kava (Piper methysticum) in unlicensed medicines. Medicines Control Agency, United Kingdom, July 19, 2002.
  5. Li XZ, Ramzan I. Role of ethanol in kava hepatotoxicity. Phytother Res 2010;24:475-80. PubMed
  6. Chanwai, L. G. Kava toxicity. Emergency Medicine 2002;12:142-145.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

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Fosphenytoin also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, kava might increase levels of CYP2C9 substrates.
In vitro research shows that kava significantly inhibits CYP2C9 enzymes. This effect has not yet 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

Here's the idea behind this pairing. Once it's in your body, fosphenytoin converts into phenytoin, and your liver relies heavily on an enzyme called CYP2C9 to clear that phenytoin out. In lab dish studies, kava appears to slow down that same enzyme. If that happened in a real person, phenytoin could build up higher than expected, and that matters a lot because phenytoin has a very narrow safe range. Too much can bring on dizziness, slurred speech, unsteady walking, double vision, drowsiness, or confusion.

I want to be honest about the strength of this, though. So far this is only seen in test tubes, not in actual patients, so it's theoretical. Kava also carries its own liver risks. Please don't change anything on your own. Just loop in your neurologist or pharmacist first.

References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed

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

Kava Also Interacts With Other Medications

Kava has 247 major, 577 moderate, 341 minor known drug interactions in our database — the Fosphenytoin one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Kava

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

Everything else you take

See Every Supplement That Interacts With Fosphenytoin

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fosphenytoin page lists 205 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 14 major · 172 moderate · 19 minor.

From our pharmacist’s overview on the Fosphenytoin page

“St. John's wort is the entry I would flag first with fosphenytoin (Cerebyx).”

Reviewed by 2 · Jul 18, 2026

Open the Fosphenytoin interaction page

One more smart check

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

We hold 403 real supplement products containing Kava, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kava. Your product may carry other ingredients that interact with Fosphenytoin too, on top of Kava — 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 Kava and Fosphenytoin 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 Kava
Top 25%

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

29 days ago today
Medication Fosphenytoin
Steady interest

#2,051 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 Kava

What is Kava?

Kava
  • Anxiety and stress
  • Restlessness
  • Trouble sleeping
  • Relaxation in social or cultural settings
  • Menopausal symptoms

Kava is a Pacific Island plant traditionally used to promote relaxation and ease anxiety, and some studies suggest it may help mild anxiety. However, kava has been linked to rare but serious liver damage, so it should be used with caution, avoided by people with liver problems, and only used after talking with your pharmacist or doctor.

Read the full Kava monograph & all interactions
Medication

About Fosphenytoin Injection

What Is Fosphenytoin Injection Used For?

Brand name: Cerebyx

Fosphenytoin injection is used to treat generalized tonic-clonic status epilepticus (a prolonged, life-threatening seizure emergency) and to prevent or treat seizures that occur during or after brain surgery. It is given by intravenous (IV) or intramuscular (IM) injection in a hospital or clinical setting.

It can also be used short-term as a substitute for oral phenytoin when a patient cannot take medicine by mouth. This use is temporary — as soon as oral phenytoin is possible again, it should replace the injection.

See full Fosphenytoin Injection drug information
Keep checking

Other Drugs & Kava

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

247Major
577Moderate
341Minor
1,664No known interaction
Major

247 interactions

Showing 60 of 247 major interactions — see all 247 on the Kava page.

Moderate

577 interactions

Showing 60 of 577 moderate interactions — see all 577 on the Kava page.

Minor

341 interactions

Showing 60 of 341 minor interactions — see all 341 on the Kava page.

No interaction 1,664 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 Kava and Fosphenytoin Together: Common Questions

Can you take Kava with Fosphenytoin?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Kava and Fosphenytoin?
Fosphenytoin belongs to more than one drug category, and Kava interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Kava and Fosphenytoin interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

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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.