Drug & supplement interaction

Fever Bark + Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine brand name: Multi Symptom Cold Relief.

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

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine falls into 3 drug categories that Fever Bark can interact with; the most serious is rated moderate. Theoretically, fever bark might increase the levels and clinical effects of CYP2D6 substrates.

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

Fever Bark and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

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

Why Are There 3 Interactions?

Fever Bark interacts with whole categories of medication. Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine falls into 3 of those categories, so it can interact with Fever Bark in 3 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 3

Why this applies to Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Fever Bark interacts with.

Theoretically, fever bark might increase the levels and clinical effects of CYP2D6 substrates.
In vitro research suggests that yohimbine, a constituent of fever bark, inhibits CYP2D6 enzyme activity. The effects of fever bark itself are unclear.
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 cold product has a few ingredients, but the one that matters here is dextromethorphan (the cough suppressant). Your body clears it using a liver enzyme called CYP2D6. Lab studies hint that yohimbine, one of the chemicals in fever bark, may slow that enzyme down. If that happens in real life, dextromethorphan could build up and lead to more drowsiness, dizziness, or feeling spacey. Chlorpheniramine, the antihistamine, also leans on CYP2D6 and can add to that sleepy, foggy feeling.

That said, this is only a theoretical concern based on test-tube research, not real human studies, and fever bark itself hasn't been tested. Fever bark also has its own effects on blood pressure and heart rate, which is a bigger reason to be cautious. Please check with your pharmacist or doctor before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. VandenBrink, B. M., Foti, R. S., Rock, D. A., Wienkers, L. C., and Wahlstrom, J. L. Prediction of CYP2D6 drug interactions from in vitro data: evidence for substrate-dependent inhibition. Drug Metab Dispos. 2012;40(1):47-53. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

2 of 3

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine also falls under CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS.

Theoretically, CYP2D6 inhibitors might increase the levels and clinical effects of yohimbine, a constituent of fever bark.
In vitro and clinical research shows that the fever bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes.
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 twist with this combo: it isn't really your cold medicine that changes the fever bark, it's the other way around. Some ingredients in this multi-symptom product, especially dextromethorphan (the cough suppressant) and to a lesser degree chlorpheniramine, can gently slow down a liver enzyme called CYP2D6. Fever bark contains a yohimbine-like alkaloid that the body clears using that same enzyme.

So in theory, taking them together could let the fever bark's yohimbine-like compounds build up a bit, which may exaggerate effects like a racing heart, jitteriness, anxiety, or a bump in blood pressure. This is only a theoretical concern based on how the chemicals behave, not proven in real patients. Still, fever bark is potent and poorly studied, so please run this past your pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Le Corre P, Parmer RJ, Kailasam MT, et al. Human sympathetic activation by alpha2-adrenergic blockade with yohimbine: Bimodal, epistatic influence of cytochrome P450-mediated drug metabolism. Clin Pharmacol Ther. 2004;76(2):139-53.
  2. Mueller-Schoell A, Michelet R, Weinelt F, Kloft C, Mikus G. CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications. Arch Toxicol. 2021. PubMed
  3. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. PubMed
Moderate

STIMULANT DRUGS

3 of 3

Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine also falls under STIMULANT DRUGS.

Theoretically, fever bark might increase or decrease the effects of stimulant drugs.
Reserpine, a constituent of fever bark, might increase or decrease effects of sympathomimetics. Also, yohimbine, another constituent of fever bark, has sympathomimetic effects and increases blood pressure in a dose-dependent manner. It is not known if this would occur with fever bark.
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

The piece of this combo cold product that matters here is the phenylpropanolamine, a decongestant that works like a stimulant by tightening blood vessels and nudging up blood pressure and heart rate. Fever bark contains plant alkaloids, including a yohimbine-like compound that can also act as a stimulant, and a reserpine-like compound that can pull the other way. So in theory, pairing them could either pile on extra stimulation (think racing heart, jitteriness, headache, a spike in blood pressure) or blunt the decongestant. Honestly, the direction is unpredictable.

I'll be straight with you: this is based on weak, anecdotal evidence, and we don't even know if whole fever bark behaves this way. Still, fever bark is risky on its own. Please run it by your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Sklar S, et al. Drug therapy screening system. Indianapolis, IN: First Data Bank 99.1-99. 2 eds.
  4. Bharucha AE, Skaar T, Andrews CN, et al Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects. Neurogastroenterol Motil. 2008;20(8):891-9. 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

Fever Bark Also Interacts With Other Medications

Fever Bark has 40 major, 673 moderate, 87 minor known drug interactions in our database — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine one above is among them. If you take anything else, check it against the full list below.

Major 40 Moderate 673 Minor 87 No known interaction 2,030 (incl. Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine)
Taking anything else?

Check Another of Your Medications Against Fever Bark

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine

This page covers Fever Bark only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine page lists 300 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), Ephedra (major) and Grapefruit (major).

By severity: 14 major · 241 moderate · 45 minor.

Open the Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine interaction page

How much people look this up

Where Fever Bark and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine 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 Fever Bark
Steady interest

#1,224 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine
Top 25%

#640 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 Fever Bark

What is Fever Bark?

Fever Bark
  • Fever
  • Diarrhea
  • Malaria (traditional)
  • Digestive complaints
  • Bitter tonic

Fever bark is the bark of the Australian tree Alstonia constricta, used in traditional medicine for fever, diarrhea, and infections. There is very little reliable human research to support these uses, and the bark contains potent alkaloids that may cause serious side effects. It is best avoided unless used under direct medical supervision.

Read the full Fever Bark monograph & all interactions
Keep checking

Other Drugs & Fever Bark

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

40Major
673Moderate
87Minor
2,029No known interaction
40 Major 673 Moderate 87 Minor 2,029 No interaction
Major

40 interactions

Moderate

673 interactions

Showing 60 of 673 moderate interactions — see all 673 on the Fever Bark page.

Minor

87 interactions

Showing 60 of 87 minor interactions — see all 87 on the Fever Bark page.

No interaction 2,029 drugs checked — show the list

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

Showing the 60 most looked-up of 2,029 medications checked with no known interaction — see the full Fever Bark list.

See the full Fever Bark interactions page
See every supplement checked against Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine, 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
Fever Bark monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine supplement interactions › Every supplement checked against Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine, 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 Fever Bark and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine Together: Common Questions

Can you take Fever Bark with Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine?
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 Fever Bark and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine?
Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine belongs to more than one drug category, and Fever Bark 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 Fever Bark and Acetaminophen, Chlorpheniramine, Dextromethorphan, Phenylpropanolamine 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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