Drug & supplement interaction

Fever Bark + Ibuprofen, Hydrocodone

Ibuprofen, Hydrocodone brand name: Ibucodone.

Moderate Interaction
The bottom line Moderate

Ibuprofen, Hydrocodone falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Fever Bark and Ibuprofen, Hydrocodone

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

Why Are There 2 Interactions?

Fever Bark interacts with whole categories of medication. Ibuprofen, Hydrocodone falls into 2 of those categories, so it can interact with Fever Bark 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

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Why this applies to Ibuprofen, Hydrocodone

Ibuprofen, Hydrocodone 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

Here's the wrinkle with this combo product. The hydrocodone half is actually a prodrug for part of its pain relief. Your body uses an enzyme called CYP2D6 to turn hydrocodone into hydromorphone, a stronger painkiller. Fever bark contains a yohimbine-like compound that, in lab dishes, appears to block that same enzyme. If that holds true in people, less hydrocodone would convert, so you might get weaker pain relief rather than more. The ibuprofen side isn't really involved here.

The honest truth is this is only a theory from test-tube work, and we don't know how fever bark behaves in the real body. Still, fever bark carries its own risky alkaloids, so please check with your pharmacist or doctor before pairing them.

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
Minor

ANTICOAGULANT/ANTIPLATELET DRUGS

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Ibuprofen, Hydrocodone also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, combining fever bark with antiplatelet or anticoagulant drugs might have additive effects; however, this has not been reported in clinical research.
Research in healthy adults shows that taking yohimbine, a constituent of fever bark, in doses of 8 mg or more, seems to inhibit platelet aggregation in vitro by binding to the alpha-2 adrenoceptor. The effects of fever bark itself are unclear.
Severity Minor 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

The combo pill you're asking about contains ibuprofen (an NSAID) plus hydrocodone (an opioid). The piece that matters here is the ibuprofen. On its own, ibuprofen makes platelets a little less sticky, so it can mildly raise your risk of bruising or bleeding. Fever bark contains yohimbine-like alkaloids that, in lab studies, also seemed to slow platelets down. Put the two together and you might, in theory, get a little extra bleeding tendency.

I want to be honest about how thin this evidence is. It comes from test-tube work, not from real people, and the effect of fever bark itself is unclear. This is a minor, theoretical concern. Still, fever bark is potent and best avoided. Please check with your pharmacist or doctor before mixing them.

References
  1. Mustonen, P., Savola, J., and Lassila, R. Atipamezole, an imidazoline-type alpha(2)-adrenoceptor inhibitor, binds to human platelets and inhibits their adrenaline-induced aggregation more effectively than yohimbine. Thromb.Res 8-1-2000;99(3):231-237.
  2. Berlin, I., Crespo-Laumonnier, B., Cournot, A., Landault, C., Aubin, F., Legrand, J. C., and Puech, A. J. The alpha 2-adrenergic receptor antagonist yohimbine inhibits epinephrine-induced platelet aggregation in healthy subjects. Clin Pharmacol.Ther. 199
  3. Braddock, L., Cowen, P. J., Elliott, J. M., Fraser, S., and Stump, K. Binding of yohimbine and imipramine to platelets in depressive illness. Psychol.Med 1986;16(4):765-773. PubMed
  4. Boon, N. A., Elliott, J. M., Grahame-Smith, D. G., John-Green, T., and Stump, K. A comparison of alpha 2-adrenoreceptor binding characteristics of intact human platelets identified by [3H]-yohimbine and [3H]- dihydroergocryptine. J Auton.Pharmacol 1983;3

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 Ibuprofen, Hydrocodone 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 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 Ibuprofen, Hydrocodone

This page covers Fever Bark only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ibuprofen, Hydrocodone page lists 356 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), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 13 major · 303 moderate · 40 minor.

From our pharmacist’s overview on the Ibuprofen, Hydrocodone page

“Mixing supplements with Ibucodone (ibuprofen plus hydrocodone) carries real risk, and 13 of the 356 ingredients on this page rate major. Ibuprofen already raises bleeding risk, so the largest cluster here, over 200 ingredients, can add to it.”

Reviewed by 2 · Jul 18, 2026

Open the Ibuprofen, Hydrocodone interaction page

How much people look this up

Where Fever Bark and Ibuprofen, Hydrocodone 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
Top half

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

29 days ago today
Medication Ibuprofen, Hydrocodone
Steady interest

#2,352 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
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
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

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Pharmacist Counseling Corner

Taking Fever Bark and Ibuprofen, Hydrocodone Together: Common Questions

Can you take Fever Bark with Ibuprofen, Hydrocodone?
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 Fever Bark and Ibuprofen, Hydrocodone?
Ibuprofen, Hydrocodone 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 Ibuprofen, Hydrocodone 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.