Drug & supplement interaction

Syrian Rue + 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 2 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Syrian Rue and Guaifenesin, Hydrocodone, Pseudoephedrine

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

Why Are There 2 Interactions?

Syrian Rue interacts with whole categories of medication. Guaifenesin, Hydrocodone, Pseudoephedrine falls into 2 of those categories, so it can interact with Syrian Rue in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 2

Why this applies to Guaifenesin, Hydrocodone, Pseudoephedrine

Guaifenesin, Hydrocodone, Pseudoephedrine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Syrian Rue interacts with.

Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP2D6.
Syrian rue contains beta-carboline alkaloids, including harmine, harmaline, harmalol, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids can inhibit CYP2D6 enzymes.
Severity Moderate Likelihood Probable Evidence D

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

This combo product has three pieces, but the one that matters here is the hydrocodone. Hydrocodone is a prodrug, meaning your body uses an enzyme called CYP2D6 to turn part of it into a stronger pain reliever. Syrian Rue's harmala alkaloids may block that same enzyme. In theory, that could mean a bit less of the active form, so the pain or cough relief might feel weaker for some people.

Keep in mind this is a theoretical concern based on lab studies, not real-world cases, so it may not happen at all. Separately, Syrian Rue acts like an MAO inhibitor, which can raise the chance of jittery, high blood pressure effects from the pseudoephedrine. I'd run this past your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Guaifenesin, Hydrocodone, Pseudoephedrine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP3A4.
Syrian rue contains beta-carboline alkaloids, including harmine, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids competitively inhibit CYP3A4 enzymes.
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 combo product pairs a cough suppressant opioid (hydrocodone) with an expectorant (guaifenesin) and a decongestant (pseudoephedrine). The piece that matters here is hydrocodone, which your liver partly processes through an enzyme called CYP3A4. Lab studies suggest Syrian Rue may slow that enzyme down. In theory, that could let hydrocodone build up a bit, nudging up effects like drowsiness, dizziness, slowed breathing, constipation, or nausea.

I'll be honest, this is theoretical and comes from test-tube data, not real patients, so I don't want to overstate it. There's a bigger worry, though: Syrian Rue acts like an MAO inhibitor, which doesn't mix well with the pseudoephedrine and opioid here. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.

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

Syrian Rue Also Interacts With Other Medications

Syrian Rue has 1,121 moderate 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 1,121 No known interaction 1,709 (incl. Guaifenesin, Hydrocodone, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Syrian Rue

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

Everything else you take

See Every Supplement That Interacts With Guaifenesin, Hydrocodone, Pseudoephedrine

This page covers Syrian Rue 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

How much people look this up

Where Syrian Rue 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 Syrian Rue
Steady interest

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

29 days ago today
Medication Guaifenesin, Hydrocodone, Pseudoephedrine
Top 25%

#411 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 Syrian Rue

What is Syrian Rue?

  • Traditional remedy for digestive complaints
  • Used as a sedative or for mood
  • Antimicrobial and antiparasitic folk use
  • Used as a dye and incense
  • Recreational psychoactive use

Syrian Rue (Peganum harmala) is a traditional plant whose seeds contain potent compounds called harmala alkaloids, including MAO-inhibiting harmine and harmaline. There is little reliable human evidence that it safely treats any condition, and it carries real risks of toxicity, so it is not recommended for self-treatment. Talk to a pharmacist or doctor before considering it.

Read the full Syrian Rue monograph & all interactions
Keep checking

Other Drugs & Syrian Rue

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

0Major
1,121Moderate
0Minor
1,708No known interaction
1,121 Moderate 1,708 No interaction
Moderate

1,121 interactions

Showing 60 of 1,121 moderate interactions — see all 1,121 on the Syrian Rue page.

No interaction 1,708 drugs checked — show the list

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

Showing the 60 most looked-up of 1,708 medications checked with no known interaction — see the full Syrian Rue list.

See the full Syrian Rue 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
Syrian Rue 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 Syrian Rue and Guaifenesin, Hydrocodone, Pseudoephedrine Together: Common Questions

Can you take Syrian Rue 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 2 interactions listed for Syrian Rue and Guaifenesin, Hydrocodone, Pseudoephedrine?
Guaifenesin, Hydrocodone, Pseudoephedrine belongs to more than one drug category, and Syrian Rue 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 Syrian Rue 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.