Drug & supplement interaction

Fever Bark + Fluoxetine

Fluoxetine brand names: Prozac, Sarafem.

Moderate Interaction
The bottom line Moderate

Fluoxetine 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 Fluoxetine

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. Fluoxetine 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 Fluoxetine

Fluoxetine 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 gist with fluoxetine (Prozac) and fever bark. Your body relies on a liver enzyme called CYP2D6 to help clear fluoxetine. Fever bark contains a yohimbine-like compound that, in a test tube, seems to slow that same enzyme down. In theory, if fluoxetine isn't broken down as quickly, more of it could linger in your system, which might bump up side effects like jitteriness, trouble sleeping, nausea, headache, or feeling wired.

I want to be honest though: this is based only on lab data, not real people taking the two together, so the actual effect is unclear and may be small. Still, fever bark's alkaloids can affect blood pressure and heart rate on their own. 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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

2 of 3

Fluoxetine also falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS.

Theoretically, CYP3A4 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 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

Here's the thing to know with fluoxetine (Prozac) and fever bark. Fluoxetine slows down a liver enzyme called CYP3A4, and that same enzyme is what your body uses to break down yohimbine, one of the active alkaloids in fever bark. So if you take them together, the yohimbine could hang around longer and build up. That's not about the fluoxetine becoming stronger, it's about the fever bark hitting harder than expected.

Higher yohimbine levels can mean a faster heartbeat, jitteriness, anxiety, and spikes in blood pressure, which is uncomfortable on its own and a poor mix when you're already taking an antidepressant. I'll be honest, this interaction is theoretical and based on how the chemicals behave, not on strong human studies. Still, fever bark is potent and poorly studied, so please check with your pharmacist or doctor before combining them.

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. 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

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

3 of 3

Fluoxetine 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 thing to know if you take Prozac (fluoxetine) and are thinking about fever bark. Fluoxetine is a strong blocker of a liver enzyme called CYP2D6, which happens to be the same enzyme that breaks down yohimbine, one of the active alkaloids in fever bark. So fluoxetine doesn't change because of the bark. Instead, the bark's yohimbine can build up because the medication is slowing its breakdown.

More yohimbine in your system can mean a faster heartbeat, jumpiness, anxiety, higher blood pressure, and trouble sleeping. I'll be honest, this is a theoretical concern based on how the chemistry works, not on solid human studies, and fever bark itself can be risky on its own. Please don't change your fluoxetine. Just check with your pharmacist or doctor before adding fever bark.

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

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 Fluoxetine 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.

From our Q&A

Questions About Fever Bark or Fluoxetine

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

This page covers Fever Bark only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fluoxetine page lists 163 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 8 major · 127 moderate · 28 minor.

From our pharmacist’s overview on the Fluoxetine page

“Grapefruit is the surprise at the top of fluoxetine's (Prozac) supplement list. In large amounts it can stretch the QT interval, the electrical pause between heartbeats, and fluoxetine, a widely prescribed antidepressant, can do the same, raising the odds of a dangerous rhythm.”

Reviewed by 2 · Jul 18, 2026

Open the Fluoxetine interaction page

How much people look this up

Where Fever Bark and Fluoxetine 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

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

29 days ago today
Medication Fluoxetine
Top 5%

#45 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
Medication

About Fluoxetine

What Is Fluoxetine Used For?

Brand names: Prozac, Sarafem

Fluoxetine is approved to treat four conditions: major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa (a binge-eating and purging disorder), and panic disorder — with or without agoraphobia (fear of situations that feel hard to escape).

It works for adults across all four conditions, and for children and teens with depression (ages 8–18) and OCD (ages 7–17).

See full Fluoxetine drug information
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 Fluoxetine Together: Common Questions

Can you take Fever Bark with Fluoxetine?
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 Fluoxetine?
Fluoxetine 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 Fluoxetine 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 Fluoxetine and Fever Bark?

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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.