Drug & supplement interaction

Fever Bark + Ibuprofen, Oxycodone

Ibuprofen, Oxycodone brand name: Combunox.

Moderate Interaction
The bottom line Moderate

Ibuprofen, Oxycodone 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, Oxycodone

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, Oxycodone 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

1 of 2

Why this applies to Ibuprofen, Oxycodone

Ibuprofen, Oxycodone 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

The combo pill Combunox pairs ibuprofen with oxycodone. The piece that matters here is the oxycodone. Your body uses an enzyme called CYP2D6 to turn oxycodone into oxymorphone, a stronger active painkiller. Fever bark contains yohimbine-like compounds that, in lab studies, can block CYP2D6. If that blocking happened in real life, it could shift how much active painkiller you make. The honest catch is this is theoretical, based only on test-tube work, and the effect of fever bark itself is unclear.

Because opioid effects (drowsiness, slowed breathing, confusion) can be serious if amplified, I'd play it safe. Please check with your pharmacist or doctor before pairing fever bark with this medication rather than guessing.

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

2 of 2

Ibuprofen, Oxycodone 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

Here's the thing with Combunox (which combines ibuprofen and oxycodone): the ibuprofen part already has a mild blood-thinning, anti-platelet effect of its own. Fever bark contains a yohimbine-like compound that, in lab studies, also seems to make platelets a little less sticky. So in theory, stacking the two together could slightly add to bleeding risk, things like easier bruising, nosebleeds, or stomach irritation that's slower to stop.

I want to be honest about how thin this evidence is. It comes from lab and animal work, not real patients, and the effect of fever bark itself hasn't been pinned down. This is a minor, mostly theoretical concern. Still, fever bark carries its own risks, so I'd run it past your pharmacist or doctor before combining 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, Oxycodone 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, Oxycodone

This page covers Fever Bark only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ibuprofen, Oxycodone 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, Oxycodone page

“Combunox puts oxycodone, an opioid, together with the NSAID ibuprofen, and I want you to read this page carefully rather than skim it. Of the 356 supplements and herbs on file, 202 can raise your bleeding risk on top of what ibuprofen already does, and 78 can deepen the drowsiness and slowed breathing that come with oxycodone.”

Reviewed by 2 · Jul 18, 2026

Open the Ibuprofen, Oxycodone interaction page

How much people look this up

Where Fever Bark and Ibuprofen, Oxycodone 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

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

29 days ago today
Medication Ibuprofen, Oxycodone
Steady interest

#1,713 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, Oxycodone Together: Common Questions

Can you take Fever Bark with Ibuprofen, Oxycodone?
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, Oxycodone?
Ibuprofen, Oxycodone 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, Oxycodone 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.