Drug & supplement interaction

Kava + Acetaminophen, Hydrocodone

Acetaminophen, Hydrocodone brand names: Vicodin, Vicodin ES, Vicodin HP, Lortab, Norco 10/325, and others.

Major Interaction
The bottom line Major

Acetaminophen, Hydrocodone falls into 6 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
Interactions6
EvidenceA
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Acetaminophen, Hydrocodone

These two interact in 6 distinct ways. Each one is explained separately below.

Why Are There 6 Interactions?

Kava interacts with whole categories of medication. Acetaminophen, Hydrocodone falls into 6 of those categories, so it can interact with Kava in 6 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 6

Why this applies to Acetaminophen, Hydrocodone

Acetaminophen, Hydrocodone 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

Your Vicodin or Norco contains hydrocodone, an opioid that already slows down your brain and breathing. Kava works in a similar calming direction, partly by boosting GABA, the body's natural brake on nerve activity. Put the two together and those effects can stack up. The concern here isn't really about how your body breaks the medicine down. It's that two sedating things at once can leave you more drowsy, foggy, dizzy, or unsteady, and in a worse case can slow your breathing too much.

This is rated a major, likely interaction, and expert guidelines say to avoid pairing kava with sedatives. There's also kava's own risk of liver harm, which matters since these pills contain acetaminophen. Please talk with your pharmacist or doctor before combining them.

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

2 of 6

Acetaminophen, Hydrocodone 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 main thing to know with your Vicodin or Norco: that acetaminophen part can be tough on the liver, especially in higher doses or if you drink alcohol. Kava has its own track record of rare liver injury, with over 100 reported cases (mostly tied to heavy or long-term use). Stacking two things that can stress the liver may add up, which is the worry here.

To be honest, this concern is mostly theoretical and based on anecdotal reports, not strong studies, so I don't want to scare you. Still, since acetaminophen is one of the most common causes of liver trouble, it's worth playing it safe. Watch for yellowing skin or eyes, dark urine, or belly pain, and check with your pharmacist or doctor before combining them.

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 2E1 (CYP2E1) SUBSTRATES

3 of 6

Acetaminophen, Hydrocodone also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Kava might increase levels of CYP2E1 substrates.
In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days inhibited the metabolism of CYP2E1 substrates.
Severity Moderate Likelihood Probable Evidence B

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 something worth knowing if you take Vicodin or Norco. Your liver uses several enzymes to process the acetaminophen portion of this combo. One of them, called CYP2E1, normally turns a small amount of acetaminophen into a byproduct that can be hard on the liver. In a small study, kava actually slowed that particular enzyme down. So this isn't a case of acetaminophen building up to dangerous blood levels.

My bigger concern is overlap, not chemistry. Both kava and the hydrocodone side can have calming, drowsy effects, so combining them may leave you more sleepy, foggy, or unsteady. And since kava itself has been tied to rare liver injury, pairing it with acetaminophen (also processed by the liver) isn't ideal. Please run this by your pharmacist or doctor before mixing them.

References
  1. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

4 of 6

Acetaminophen, Hydrocodone also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

It is unclear if kava inhibits CYP1A2; research is conflicting.
Although in vitro research and a case report suggest that kava inhibits CYP1A2, more robust clinical evidence shows that kava has no effect on CYP1A2. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP1A2 activity.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the honest picture: this interaction is built around the idea that kava might block an enzyme called CYP1A2. The thing is, Vicodin and Norco (acetaminophen with hydrocodone) don't really rely on CYP1A2 to do their job. Hydrocodone is handled mainly by other liver enzymes, and acetaminophen mostly goes through different pathways too. So this particular enzyme concern is a weak fit here, and the better clinical evidence suggests kava doesn't meaningfully affect CYP1A2 anyway.

What I'd actually keep an eye on is that both kava and this medication can make you drowsy, so stacking them could leave you more sleepy or foggy. Kava can also stress the liver, and so can the acetaminophen part. Please check with your pharmacist or doctor before combining them.

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
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Toohey TP, Lu BY, Wada C. Toxic effects of psychotropics related to possible p450 enzyme inhibition by kava:report of 2 cases. Prim Care Companion CNS Disord 2013;15(5). PubMed
  5. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

5 of 6

Acetaminophen, Hydrocodone also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

It is unclear if kava inhibits CYP1A2; research is conflicting.
In vitro research shows that kava extract significantly inhibits CYP2D6. However, clinical research shows that kava does not affect the metabolism of CYP2D6 substrates in humans.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the practical scoop on combining kava with your Norco (acetaminophen and hydrocodone). The hydrocodone part is actually a prodrug, meaning your liver uses an enzyme called CYP2D6 to turn it into the stronger painkiller your body feels. In test-tube studies, kava looked like it could block that enzyme, which in theory might mean less pain relief. The good news: when this was actually studied in real people, kava did not meaningfully change how CYP2D6 drugs are handled. So this interaction is rated minor and unlikely.

The bigger thing I'd flag is overlap in effects. Both kava and hydrocodone can cause drowsiness, and both can stress your liver, as can the acetaminophen. Please check with your pharmacist or doctor before combining them.

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
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
  5. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

6 of 6

Acetaminophen, Hydrocodone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if kava inhibits CYP3AA; research is conflicting.
Although in vitro research suggests that kava inhibits CYP3A4, more robust clinical evidence shows that kava has no effect on CYP3A4. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP3A4 activity.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the good news on combining kava with your Norco or Vicodin (acetaminophen plus hydrocodone). Early test-tube studies hinted that kava might slow down a liver enzyme called CYP3A4, which helps process hydrocodone. If that were true, your medicine could build up and lead to stronger effects like extra drowsiness, slowed breathing, or constipation. But a more reliable human study found that kava really doesn't change CYP3A4 activity, so this enzyme-based interaction is rated minor and unlikely.

The bigger thing I'd flag is overlap in effects. Both kava and hydrocodone are calming, so together they can make you sleepier or foggier. Kava can also stress the liver, and your tablet already contains acetaminophen, which is hard on the liver too. Please check with your pharmacist or doctor before pairing them.

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
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.

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 Acetaminophen, Hydrocodone 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 Acetaminophen, Hydrocodone

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Hydrocodone page lists 270 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 215 moderate · 44 minor.

From our pharmacist’s overview on the Acetaminophen, Hydrocodone page

“Someone taking hydrocodone with acetaminophen (Vicodin, Norco) for post-surgical or dental pain often reaches for a sleep aid, kava, or a glass of wine at night, and that is exactly where the risk sits. This combination calls for genuine vigilance.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Hydrocodone 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 Acetaminophen, Hydrocodone 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 Acetaminophen, Hydrocodone 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%

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

29 days ago today
Medication Acetaminophen, Hydrocodone
Top half

#1,374 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
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

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Pharmacist Counseling Corner

Taking Kava and Acetaminophen, Hydrocodone Together: Common Questions

Can you take Kava with Acetaminophen, Hydrocodone?
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 6 interactions listed for Kava and Acetaminophen, Hydrocodone?
Acetaminophen, Hydrocodone 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 Acetaminophen, Hydrocodone 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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