Drug & supplement interaction

Valerian + Guaifenesin, Hydrocodone, Pseudoephedrine

Guaifenesin, Hydrocodone, Pseudoephedrine brand names: Tussi-Organidin DM NR, Entuss-D.

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

Guaifenesin, Hydrocodone, Pseudoephedrine falls into 3 drug categories that Valerian can interact with; the most serious is rated moderate. Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.

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

Valerian and Guaifenesin, Hydrocodone, Pseudoephedrine

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. Guaifenesin, Hydrocodone, Pseudoephedrine 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

CNS DEPRESSANTS

1 of 3

Why this applies to Guaifenesin, Hydrocodone, Pseudoephedrine

Guaifenesin, Hydrocodone, Pseudoephedrine falls under CNS DEPRESSANTS — the group Valerian interacts with.

Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
Theoretically, concomitant use of valerian and drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.
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

This combination cough product contains hydrocodone, an opioid that can make you drowsy and slow your breathing. Valerian is a calming herb that may gently boost GABA activity in the brain, the same kind of calming signal opioids lean on. Put them together and the sleepy effects can stack up. You might feel more groggy, dizzy, or foggy than usual, and in larger amounts that added sedation matters more.

To be fair, this concern comes mostly from lab and animal work, so it's more of a theoretical caution than a proven, dramatic reaction. Still, since hydrocodone already causes real drowsiness, I'd play it safe. Check with your pharmacist or doctor before pairing valerian with this medicine, especially before driving.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999;51:505-12. PubMed
  2. Yuan CS, Mehendale S, Xiao Y, et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004;98:353-8. PubMed
  3. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009 Dec;23:1795-6.
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 3

Guaifenesin, Hydrocodone, Pseudoephedrine 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 enzyme-level concern is pretty much a non-issue. Although early lab studies hinted that valerian might tinker with CYP2D6 (one of the liver enzymes that activates the hydrocodone in this combo product into its stronger painkilling form), actual human studies didn't find any meaningful effect. So valerian is very unlikely to change how much active opioid you get.

What I would keep an eye on instead is simple overlap. Valerian is a mild relaxant and hydrocodone already causes drowsiness, so together they could leave you sleepier or foggier than usual. The pseudoephedrine in this product can do the opposite and keep you wired. It's worth a quick chat with your pharmacist before combining them.

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

Guaifenesin, Hydrocodone, Pseudoephedrine 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

Here's the good news on this combo. The interaction on file is about valerian and the CYP3A4 enzyme, which helps your body process the hydrocodone part of this cough and cold product. In real-world studies, valerian had little to no meaningful effect on that enzyme, so it's not expected to make your hydrocodone build up to dangerous levels.

That said, I'd keep a different point in mind. Valerian is a mild sedative, and hydrocodone is an opioid that already causes drowsiness. Stacking the two could leave you feeling extra sleepy, foggy, or dizzy. Go easy, avoid driving until you know how you feel, and check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Guaifenesin, Hydrocodone, Pseudoephedrine one above is among them. If you take anything else, check it against the full list below.

Moderate 337 Minor 564 No known interaction 1,929 (incl. Guaifenesin, Hydrocodone, Pseudoephedrine)
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 Guaifenesin, Hydrocodone, Pseudoephedrine

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 Guaifenesin, Hydrocodone, Pseudoephedrine, 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 Guaifenesin, Hydrocodone, Pseudoephedrine

This page covers Valerian only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Guaifenesin, Hydrocodone, Pseudoephedrine page lists 241 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), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 13 major · 190 moderate · 38 minor.

From our pharmacist’s overview on the Guaifenesin, Hydrocodone, Pseudoephedrine page

“Tussi-Organidin DM NR (guaifenesin, hydrocodone, and pseudoephedrine) pairs an opioid cough suppressant with a stimulant decongestant, and that pairing is why its 241-ingredient interaction list warrants genuine care, starting with the 13 rated major. The list pulls in two directions at once.”

Reviewed by 2 · Jul 18, 2026

Open the Guaifenesin, Hydrocodone, Pseudoephedrine 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 Guaifenesin, Hydrocodone, Pseudoephedrine 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 Guaifenesin, Hydrocodone, Pseudoephedrine 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%

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

29 days ago today
Medication Guaifenesin, Hydrocodone, Pseudoephedrine
Steady interest

#1,690 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
337 Moderate 564 Minor 1,928 No 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

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

Showing the 60 most looked-up of 1,928 medications checked with no known interaction — see the full Valerian list.

See the full Valerian interactions page
See every supplement checked against Guaifenesin, Hydrocodone, Pseudoephedrine, 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
Valerian monograph › Uses, safety, and every drug interaction in one place Guaifenesin, Hydrocodone, Pseudoephedrine supplement interactions › Every supplement checked against Guaifenesin, Hydrocodone, Pseudoephedrine, 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 Valerian and Guaifenesin, Hydrocodone, Pseudoephedrine Together: Common Questions

Can you take Valerian with Guaifenesin, Hydrocodone, Pseudoephedrine?
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 Guaifenesin, Hydrocodone, Pseudoephedrine?
Guaifenesin, Hydrocodone, Pseudoephedrine 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 Guaifenesin, Hydrocodone, Pseudoephedrine 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.