Drug & supplement interaction

Valerian + Acetaminophen, Dextromethorphan

Acetaminophen, Dextromethorphan brand name: Tylenol Cough Ex Strength.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Dextromethorphan falls into 3 drug categories that Valerian can interact with; the most serious is rated moderate. Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.

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

Valerian and Acetaminophen, Dextromethorphan

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

Why Are There 3 Interactions?

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

Moderate

GLUCURONIDATED DRUGS

1 of 3

Why this applies to Acetaminophen, Dextromethorphan

Acetaminophen, Dextromethorphan falls under GLUCURONIDATED DRUGS — the group Valerian interacts with.

Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
In vitro research shows that methanolic valerian extract and valerenic acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) and UGT2B7.
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 gist with your Tylenol Cough Ex Strength (acetaminophen and dextromethorphan). Acetaminophen is partly cleared by a process called glucuronidation, which is basically how your liver tags certain drugs so you can clear them out. Lab and animal studies hint that valerian might weakly slow that tagging step, which could in theory let a little more acetaminophen linger in your system.

I want to be honest about how thin this evidence is. It comes from test-tube research, not real patients, and the effect looks mild. For most people taking this product as directed, valerian is unlikely to cause a noticeable problem. Just don't exceed the daily acetaminophen limit, and run it by your pharmacist or doctor first to be safe.

References
  1. Alkharfy, K. M. and Frye, R. F. Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro. Xenobiotica 2007;37(2):113-123.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP2D6.
Although some in vitro evidence suggests that valerian affects CYP2D6, clinical pharmacokinetic (PK) studies show that valerian is unlikely to affect the CYP2D6 enzyme. In one PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days did not affect the metabolism of dextromethorphan, a CYP2D6 substrate. In another PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of debrisoquine, an accepted CYP2D6 probe-substrate.
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

Good news here: the worry about Valerian and the dextromethorphan in your Tylenol Cough product is more of a theoretical one than a real-world problem. Dextromethorphan is cleared by a liver enzyme called CYP2D6, and early lab tests hinted that Valerian might slow that enzyme down. If it actually did, dextromethorphan could build up and cause more drowsiness or dizziness.

But the actual human studies don't bear that out. When people took Valerian nightly alongside dextromethorphan, it did not meaningfully change how the body handled the drug. The acetaminophen side isn't affected by this either. One sensible note: both Valerian and these cough products can make you sleepy, so you may feel a bit more drowsy together. If that worries you, check with your pharmacist.

References
  1. Donovan JL, DeVane CL, Chavin KD, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:1333-6. PubMed
  2. 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
  3. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007 Nov;101:350-8.
  4. Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007 Jan;100:23-30. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
Although some in vitro evidence suggests that valerian extract might inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show that valerian does not have a clinically significant effect on the CYP3A4 enzyme. In one PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of midazolam, an accepted CYP3A4 probe-substrate. In another PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days modestly increases levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of CYP3A4. However, this mild inhibition is unlikely to be clinically relevant.
Severity Minor Likelihood Possible Evidence B

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

Good news here: the combination of Valerian with your Tylenol Cough product (acetaminophen plus dextromethorphan) is considered a minor concern. While some lab studies hinted that Valerian might slow down the CYP3A4 enzyme that helps break down dextromethorphan, real-world human studies show Valerian has little to no meaningful effect on that enzyme. So in practice, Valerian is very unlikely to cause your cough medicine to build up.

That said, both Valerian and dextromethorphan can have a mild calming or drowsy effect on their own. Taking them together could leave you feeling a bit more sleepy or foggy than usual. If you notice that, take it easy and check in with your pharmacist or doctor.

References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. Lefebvre T, Foster BC, Drouin CE, et al. In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharmaceut Sci 2004;7:265-73.
  3. Donovan JL, DeVane CL, Chavin KD, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:1333-6. PubMed
  4. 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
  5. Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007 Jan;100:23-30. 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

Valerian Also Interacts With Other Medications

Valerian has 337 moderate, 564 minor known drug interactions in our database — the Acetaminophen, Dextromethorphan 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 Valerian

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

From our Q&A

Questions About Valerian or Acetaminophen, Dextromethorphan

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Valerian or Acetaminophen, Dextromethorphan, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Dextromethorphan

This page covers Valerian only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Dextromethorphan page lists 236 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), Grapefruit (major) and Lithium (major).

By severity: 8 major · 185 moderate · 43 minor.

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

“Alcohol tops my worry list for Acetaminophen with Dextromethorphan (Tylenol Cough Ex Strength). Beer and wine both carry major ratings, since acetaminophen already asks a lot of the liver and regular drinking compounds that strain.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Dextromethorphan interaction page

One more smart check

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

We hold 2,185 real supplement products containing Valerian, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Valerian. Your product may carry other ingredients that interact with Acetaminophen, Dextromethorphan too, on top of Valerian — 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 Valerian and Acetaminophen, Dextromethorphan 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 Valerian
Top 10%

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

29 days ago today
Medication Acetaminophen, Dextromethorphan
Top 5%

#79 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 Valerian

What is Valerian?

Valerian
  • Insomnia and poor sleep
  • Anxiety and stress
  • Restlessness
  • Muscle tension or cramps
  • Menstrual discomfort

Valerian is an herb whose root is widely used as a natural sleep aid and for calming nerves. The evidence is mixed and often weak, so it may help some people sleep but does not work reliably for everyone. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before starting it.

Read the full Valerian monograph & all interactions
Keep checking

Other Drugs & Valerian

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

0Major
337Moderate
564Minor
1,928No known interaction
Moderate

337 interactions

Showing 60 of 337 moderate interactions — see all 337 on the Valerian page.

Minor

564 interactions

Showing 60 of 564 minor interactions — see all 564 on the Valerian page.

No interaction 1,928 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 Valerian and Acetaminophen, Dextromethorphan Together: Common Questions

Can you take Valerian with Acetaminophen, Dextromethorphan?
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 Valerian and Acetaminophen, Dextromethorphan?
Acetaminophen, Dextromethorphan belongs to more than one drug category, and Valerian 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 Valerian and Acetaminophen, Dextromethorphan 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

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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.