Drug & supplement interaction

Bitter Orange + Guaifenesin

Guaifenesin brand names: Robitussin, Humibid LA, Amibid LA, Numobid, Muco-Fen 800, and others.

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

Bitter Orange has a moderate interaction with Guaifenesin. Bitter orange might increase blood levels of dextromethorphan.

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

Bitter Orange and Guaifenesin

Here is the interaction we found between these two, with the evidence behind it.

Moderate

DEXTROMETHORPHAN (Robitussin DM, others)

Bitter orange might increase blood levels of dextromethorphan.
One small clinical study shows that bitter orange juice increases dextromethorphan levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for dextromethorphan-related adverse effects.
Severity Moderate 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 something worth clearing up. The interaction on file is really about dextromethorphan, the cough suppressant that often shares a bottle with guaifenesin in those combo cough products. Guaifenesin itself is just an expectorant, so it works by loosening mucus so you can cough it up, and it isn't broken down by CYP3A4 the way dextromethorphan is.

So for plain guaifenesin (like Mucinex or Humibid), bitter orange isn't expected to meaningfully change how it works or raise your risk of side effects. If your product is actually a "DM" combo containing dextromethorphan, that's where bitter orange could nudge levels up a bit. When in doubt, check the label and ask your pharmacist what's in your bottle.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. 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

Bitter Orange Also Interacts With Other Medications

Bitter Orange has 10 major, 877 moderate, 71 minor known drug interactions in our database — the Guaifenesin one above is one of them. If you take anything else, check it against the full list below.

Major 10 Moderate 877 Minor 71 No known interaction 1,872 (incl. Guaifenesin)
Taking anything else?

Check Another of Your Medications Against Bitter Orange

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

From our Q&A

Questions About Bitter Orange or Guaifenesin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Bitter Orange or Guaifenesin, 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

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Guaifenesin page lists 26 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Berberine (moderate), Coffee Charcoal (moderate) and Corydalis Yanhusuo (moderate).

By severity: 2 major · 15 moderate · 9 minor.

From our pharmacist’s overview on the Guaifenesin page

“Guaifenesin (Robitussin, Humibid LA) loosens chest mucus, and by itself it is a mild medicine, but two of the 26 supplements on this list rate major, so those two deserve your attention first. Activated charcoal can bind the drug in your gut and blunt what it does, and grapefruit raises blood levels of dextromethorphan, the cough suppr…”

Reviewed by 2 · Jul 18, 2026

Open the Guaifenesin interaction page

One more smart check

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

We hold 1,000 real supplement products containing Bitter Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bitter Orange. Your product may carry other ingredients that interact with Guaifenesin too, on top of Bitter Orange — 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 Bitter Orange and Guaifenesin 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 Bitter Orange
Top 25%

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

29 days ago today
Medication Guaifenesin
Steady interest

#2,336 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 Bitter Orange

What is Bitter Orange?

Bitter Orange
  • Weight loss
  • Athletic performance and energy
  • Digestive upset
  • Appetite control
  • Aromatherapy for stress (neroli oil)

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance is limited, and because it can raise heart rate and blood pressure, people with heart problems, high blood pressure, or who are pregnant should avoid it. Talk to your pharmacist or doctor before using it, especially if you take other stimulants.

Read the full Bitter Orange monograph & all interactions
Medication

About Guaifenesin

What Is Guaifenesin Used For?

Brand names: Robitussin, Humibid LA, Amibid LA, Numobid, Muco-Fen 800, Bidex, Organidin, X-pect, Mucinex

Guaifenesin helps loosen phlegm (mucus) and thin bronchial secretions — the thick fluid in your airways — so your body can clear them out more easily and make coughs more productive.

It is available in multiple forms and brands, including oral solutions, regular tablets, and extended-release tablets, all for this same purpose of relieving chest congestion.

See full Guaifenesin drug information
Keep checking

Other Drugs & Bitter Orange

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

10Major
877Moderate
71Minor
1,871No known interaction
10 Major 877 Moderate 71 Minor 1,871 No interaction
Major

10 interactions

Moderate

877 interactions

Showing 60 of 877 moderate interactions — see all 877 on the Bitter Orange page.

Minor

71 interactions

Showing 60 of 71 minor interactions — see all 71 on the Bitter Orange page.

No interaction 1,871 drugs checked — show the list

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

Showing the 60 most looked-up of 1,871 medications checked with no known interaction — see the full Bitter Orange list.

See the full Bitter Orange interactions page
See every supplement checked against Guaifenesin, 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
Bitter Orange monograph › Uses, safety, and every drug interaction in one place Guaifenesin supplement interactions › Every supplement checked against Guaifenesin, ranked by severity Guaifenesin 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 Bitter Orange and Guaifenesin Together: Common Questions

Can you take Bitter Orange with Guaifenesin?
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.
How serious is the Bitter Orange and Guaifenesin 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 Guaifenesin and Bitter Orange?

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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.