Drug & supplement interaction

Kava + Aspirin, Butalbital, Caffeine

Aspirin, Butalbital, Caffeine brand name: Fiorinal.

Minor Interaction
Medically reviewed by · Updated October 2026
The bottom line Minor

Aspirin, Butalbital, Caffeine falls into 2 drug categories that Kava can interact with; the most serious is rated minor. It is unclear if kava inhibits CYP1A2; research is conflicting.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Aspirin, Butalbital, Caffeine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Kava interacts with whole categories of medication. Aspirin, Butalbital, Caffeine falls into 2 of those categories, so it can interact with Kava in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Aspirin, Butalbital, Caffeine

Aspirin, Butalbital, Caffeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Kava interacts with.

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

If you take Fiorinal (aspirin, butalbital, and caffeine) and you're curious about kava, here's the honest picture. The caffeine piece of this combo is cleared by a liver enzyme called CYP1A2. There was some early lab work and a single case report hinting that kava might slow that enzyme down, which could let caffeine linger a bit longer and leave you feeling jittery, restless, or wide awake. But the better human research found kava had no real effect on CYP1A2 at all.

So this is a minor, unlikely concern based on conflicting, low-quality evidence. The bigger thing I'd actually flag is that both kava and butalbital can stress the liver and cause drowsiness, so please run this combination by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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 3A4 (CYP3A4) SUBSTRATES

2 of 2

Aspirin, Butalbital, Caffeine 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

Let's talk about combining kava with Fiorinal (the aspirin, butalbital, and caffeine combo for tension headaches). On paper, there was a worry that kava might block an enzyme called CYP3A4, which helps your body process certain medications. If that blocking were real, the butalbital part (a barbiturate that calms the nervous system) could build up and leave you more drowsy or foggy than expected.

Here's the reassuring part: better-quality human research found that kava did not actually affect CYP3A4. So this particular interaction is rated minor and unlikely. The bigger thing I'd watch is that both kava and butalbital can make you sleepy, so together you may feel extra drowsy. Kava can also stress the liver, and so can regular aspirin use. Please check with your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
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 248 major, 581 moderate, 337 minor known drug interactions in our database — the Aspirin, Butalbital, Caffeine one above is among them. If you take anything else, check it against the full list below.

Major 248 Moderate 581 Minor 337 No known interaction 1,664 (incl. Aspirin, Butalbital, Caffeine)
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 Aspirin, Butalbital, Caffeine

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Butalbital, Caffeine page lists 347 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Ephedra (major).

By severity: 13 major · 285 moderate · 49 minor.

From our pharmacist’s overview on the Aspirin, Butalbital, Caffeine page

“The aspirin inside Fiorinal (aspirin, butalbital, caffeine) is the reason this list deserves careful reading rather than a quick skim. More than 200 of the supplements and herbs on file can thin the blood further and raise bleeding risk on top of aspirin's own antiplatelet effect, and even ordinary alcohol, beer and wine included, carr…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, Caffeine 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%

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

29 days ago today
Medication Aspirin, Butalbital, Caffeine
Top 5%

#99 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 Aspirin, Butalbital, and Caffeine

What Is Aspirin, Butalbital, and Caffeine Used For?

Brand name: Fiorinal

This combination is used to relieve the symptoms of tension (or muscle contraction) headache. The supported product is the oral capsule.

There is no evidence that it works or is safe for multiple recurrent headaches. Caution is needed because butalbital is habit-forming and can be abused.

See full Aspirin, Butalbital, and Caffeine 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.

248Major
581Moderate
337Minor
1,663No known interaction
248 Major 581 Moderate 337 Minor 1,663 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the Kava page.

Moderate

581 interactions

Showing 60 of 581 moderate interactions — see all 581 on the Kava page.

Minor

337 interactions

Showing 60 of 337 minor interactions — see all 337 on the Kava page.

No interaction 1,663 drugs checked — show the list

We also checked Kava against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,663 medications checked with no known interaction — see the full Kava list.

See the full Kava interactions page
See every supplement checked against Aspirin, Butalbital, Caffeine, ranked by severity
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
Kava monograph › Uses, safety, and every drug interaction in one place Aspirin, Butalbital, Caffeine supplement interactions › Every supplement checked against Aspirin, Butalbital, Caffeine, ranked by severity Aspirin, Butalbital, and Caffeine drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Kava and Aspirin, Butalbital, Caffeine Together: Common Questions

Can you take Kava with Aspirin, Butalbital, Caffeine?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Kava and Aspirin, Butalbital, Caffeine?
Aspirin, Butalbital, Caffeine 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 Aspirin, Butalbital, Caffeine interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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

Still Have a Question About Aspirin, Butalbital, Caffeine and Kava?

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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.