Drug & supplement interaction

Kava + Acetaminophen, Orphenadrine

Acetaminophen, Orphenadrine brand name: Orfenagesic.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Acetaminophen, Orphenadrine falls into 3 drug categories that Kava can interact with; the most serious is rated moderate. Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Kava and Acetaminophen, Orphenadrine

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. Acetaminophen, Orphenadrine 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 (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 3

Why this applies to Acetaminophen, Orphenadrine

Acetaminophen, Orphenadrine falls under HEPATOTOXIC DRUGS — the group Kava interacts with.

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 concern with combining kava and Orfenagesic (which contains acetaminophen plus orphenadrine). The worry centers on your liver. Acetaminophen is one of the most common causes of liver strain when taken in high doses or with other things that tax the liver, and kava has been tied to rare cases of liver damage. Put them together and you're theoretically stacking two stresses on the same organ.

To be fair, this is based on scattered case reports, not strong studies, so it's more of a caution than a sure thing. Still, watch for warning signs like yellowing skin or eyes, dark urine, unusual tiredness, or belly pain on the right side. Before mixing these, please check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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

2 of 3

Acetaminophen, Orphenadrine 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 part that matters with this combo: the acetaminophen in your Orfenagesic is partly broken down by a liver enzyme called CYP2E1. A study found that kava can slow down that enzyme. Normally CYP2E1 turns a small amount of acetaminophen into a harsh byproduct that's hard on the liver. So in theory, kava slowing this pathway isn't necessarily more dangerous for the liver from acetaminophen alone.

The real concern is the liver itself. Kava has been linked to rare but serious liver injury, and acetaminophen is also processed by the liver, so stacking them adds strain. Watch for yellowing skin or eyes, dark urine, belly pain, or unusual tiredness. The orphenadrine side can also pile onto kava's drowsiness. Please talk with your pharmacist or doctor before combining these.

Contact Dr. Brian directly if you have additional questions on this interaction
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

3 of 3

Acetaminophen, Orphenadrine 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 short version on combining kava with this acetaminophen and orphenadrine combo: the theoretical concern is that kava might slow down a liver enzyme called CYP1A2, which helps process certain medicines. If that happened, levels of the drug could creep up a bit, possibly adding to drowsiness, dry mouth, dizziness, or blurred vision from the orphenadrine part.

The good news is the evidence here is weak and conflicting. A solid human study found kava had no meaningful effect on CYP1A2, so this interaction is rated minor and unlikely. What I'd really watch is the liver. Both kava and acetaminophen can stress the liver, so that overlap matters more than the enzyme question. Please check with your pharmacist or doctor before pairing 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. 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.

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, 576 moderate, 341 minor known drug interactions in our database — the Acetaminophen, Orphenadrine one above is among them. If you take anything else, check it against the full list below.

Major 248 Moderate 576 Minor 341 No known interaction 1,665 (incl. Acetaminophen, Orphenadrine)
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, Orphenadrine

This page covers Kava only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Orphenadrine page lists 160 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), Procaine (major) and Siberian Cocklebur (major).

By severity: 6 major · 119 moderate · 35 minor.

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

“Orfenagesic combines acetaminophen with orphenadrine, a muscle relaxant, and the acetaminophen half is what makes its interaction list worth real vigilance. Six of the 160 supplement ingredients on file carry a major rating, and the largest risky cluster, 38 ingredients including beer and wine, adds to the strain acetaminophen already…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Orphenadrine 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, Orphenadrine 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, Orphenadrine 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%

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

29 days ago today
Medication Acetaminophen, Orphenadrine
Top half

#1,156 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.

248Major
576Moderate
341Minor
1,664No known interaction
248 Major 576 Moderate 341 Minor 1,664 No interaction
Major

248 interactions

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

Moderate

576 interactions

Showing 60 of 576 moderate interactions — see all 576 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

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 1,664 medications checked with no known interaction — see the full Kava list.

See the full Kava interactions page
See every supplement checked against Acetaminophen, Orphenadrine, 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 Acetaminophen, Orphenadrine supplement interactions › Every supplement checked against Acetaminophen, Orphenadrine, ranked by severity 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 Acetaminophen, Orphenadrine Together: Common Questions

Can you take Kava with Acetaminophen, Orphenadrine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Kava and Acetaminophen, Orphenadrine?
Acetaminophen, Orphenadrine 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, Orphenadrine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Acetaminophen, Orphenadrine 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.