Drug & supplement interaction

Kava + Acetaminophen, Butalbital, Codeine

Acetaminophen, Butalbital, Codeine brand name: Bancap w/ Codeine.

Major Interaction
The bottom line Major

Acetaminophen, Butalbital, Codeine falls into 5 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
Interactions5
EvidenceA
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Acetaminophen, Butalbital, Codeine

These two interact in 5 distinct ways. Each one is explained separately below.

Why Are There 5 Interactions?

Kava interacts with whole categories of medication. Acetaminophen, Butalbital, Codeine falls into 5 of those categories, so it can interact with Kava in 5 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 5

Why this applies to Acetaminophen, Butalbital, Codeine

Acetaminophen, Butalbital, Codeine 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 watch with this combination. Your pain medicine already has two ingredients that calm the nervous system: butalbital (a barbiturate) and codeine (an opioid). Both make you sleepy and slow your breathing and reflexes. Kava works in a similar calming direction in the brain, so stacking them tends to pile on those effects rather than cancel them out.

Together you could feel unusually drowsy, foggy, dizzy, or unsteady on your feet, and in a worst case your breathing could slow too much. This is a well-supported, real concern, not just a theory, and expert guidelines say to avoid mixing kava with sedating medicines. Kava can also stress the liver, and acetaminophen does too, so that's another reason to be cautious. Please talk with your pharmacist or doctor before using both.

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 5

Acetaminophen, Butalbital, Codeine 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

The concern here isn't really about how these two interact in your bloodstream. It's about your liver. Kava has been tied to rare but serious liver injury, mostly with heavy or long-term use. Your combination pill contains acetaminophen (the same medicine as Tylenol), which is also processed by the liver and can stress it, especially in higher doses or with alcohol. Stacking kava on top of that may add to the strain.

This is a theoretical, anecdote-level worry, not something proven in studies, so I don't want to alarm you. Still, watch for signs like yellowing skin or eyes, dark urine, belly pain, or unusual tiredness. Please check with your pharmacist or doctor before pairing these.

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 5

Acetaminophen, Butalbital, Codeine 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 the piece that matters most with this combo product: it contains acetaminophen (Tylenol). Kava appears to slow down a liver enzyme called CYP2E1, which is one route the body uses to break down acetaminophen. When that pathway is blocked, more acetaminophen may shift toward a byproduct that is harder on the liver. Since kava itself has been tied to rare but serious liver injury, stacking the two is a double hit on the same organ.

On top of that, the codeine and butalbital here are both calming, drowsy-type ingredients, and kava can add to that sedation. Please don't pair these on your own. Talk with your pharmacist or doctor first, especially if you have any liver concerns or feel extra groggy.

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 5

Acetaminophen, Butalbital, Codeine 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

Let me put your mind at ease on this one. The interaction on file flags this combo pill (which contains acetaminophen, butalbital, and codeine) as a CYP1A2 substrate, and the concern was whether kava might slow that enzyme down. But the better-quality human research found kava did not meaningfully affect CYP1A2, so this is rated minor and unlikely.

That said, I'd still be careful here for a different reason: both kava and this medicine can make you drowsy and relaxed. Codeine and butalbital already cause sleepiness, slowed breathing, and foggy thinking, and kava's calming effect could pile on top. There's also a shared liver worry, since both kava and acetaminophen can stress the liver. 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 5

Acetaminophen, Butalbital, Codeine 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 thing about this combo pill: the codeine part actually needs your body's CYP2D6 enzyme to switch it into its pain-relieving form (that makes codeine a prodrug). In a test tube, kava looked like it could block CYP2D6, which in theory might mean less pain relief from the codeine. But the better news is that when this was studied in actual people, kava didn't meaningfully change how CYP2D6 medications were handled. So the real-world effect here looks small and unlikely.

What I'd weigh more heavily is overlap, not enzymes. Kava is calming and so is the butalbital (and codeine) in this pill, so stacking them could leave you extra drowsy or foggy. Kava can also stress the liver, and this medicine already contains acetaminophen, which the liver processes too. Please run this past 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.

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, Butalbital, Codeine 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, Butalbital, Codeine

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine page lists 240 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: 9 major · 191 moderate · 40 minor.

Open the Acetaminophen, Butalbital, Codeine 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, Butalbital, Codeine 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, Butalbital, Codeine 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%

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine
Steady interest

#1,646 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

Keep exploring
Pharmacist Counseling Corner

Taking Kava and Acetaminophen, Butalbital, Codeine Together: Common Questions

Can you take Kava with Acetaminophen, Butalbital, Codeine?
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 5 interactions listed for Kava and Acetaminophen, Butalbital, Codeine?
Acetaminophen, Butalbital, Codeine 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, Butalbital, Codeine 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.