Drug & supplement interaction

Fever Bark + Berotralstat Hydrochloride

Berotralstat Hydrochloride brand name: Orladeyo.

Moderate Interaction
The bottom line Moderate

Berotralstat Hydrochloride falls into 2 drug categories that Fever Bark can interact with; the most serious is rated moderate. Theoretically, CYP3A4 inhibitors might increase the levels and clinical effects of yohimbine, a constituent of fever bark.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Fever Bark and Berotralstat Hydrochloride

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. Berotralstat Hydrochloride 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 3A4 (CYP3A4) INHIBITORS

1 of 2

Why this applies to Berotralstat Hydrochloride

Berotralstat Hydrochloride falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Fever Bark interacts with.

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 angle that matters for this combo. Orladeyo (berotralstat), the medication you take to prevent hereditary angioedema attacks, gently blocks a liver enzyme called CYP3A4. Fever bark contains yohimbine, a plant chemical that the body clears using that same CYP3A4 enzyme. So in theory, taking them together could slow how fast yohimbine leaves your system, letting it build up.

If that happens, you'd feel the yohimbine's effects more, not the Orladeyo's. Yohimbine can raise blood pressure, speed up your heart, and cause jitteriness, anxiety, or trouble sleeping. This is only a theoretical concern based on how the drugs work, not proven in people. Still, fever bark's strong alkaloids are risky on their own, so please check with your pharmacist or doctor before using it.

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

2 of 2

Berotralstat Hydrochloride 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 understand with this pairing: the concern isn't really about your Orladeyo (berotralstat) being affected. It works the other way around. Berotralstat blocks an enzyme called CYP2D6, which happens to be the same enzyme your body uses to clear yohimbine, one of the alkaloids in fever bark.

So if you took both, the yohimbine could pile up instead of being broken down normally. That might lead to yohimbine-type effects like a racing heart, jitteriness, anxiety, sweating, or higher blood pressure. Honestly, this is mostly a theoretical worry based on how the chemistry works, not strong human studies. But fever bark is potent and poorly studied to begin with, so I'd skip it and check with your pharmacist or doctor first.

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 Berotralstat Hydrochloride 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 Berotralstat Hydrochloride

This page covers Fever Bark only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Berotralstat Hydrochloride page lists 75 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 · 51 moderate · 16 minor.

From our pharmacist’s overview on the Berotralstat Hydrochloride page

“If you take berotralstat (Orladeyo) to prevent hereditary angioedema attacks, this list deserves real attention, and the eight major-rated entries are where to start. The biggest cluster, 37 ingredients, affects the gut pump that moves berotralstat into your body; St.”

Reviewed by 2 · Jul 18, 2026

Open the Berotralstat Hydrochloride interaction page

How much people look this up

Where Fever Bark and Berotralstat Hydrochloride 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

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

29 days ago today
Medication Berotralstat Hydrochloride
Top half

#997 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 Berotralstat Hydrochloride Together: Common Questions

Can you take Fever Bark with Berotralstat Hydrochloride?
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 Berotralstat Hydrochloride?
Berotralstat Hydrochloride 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 Berotralstat Hydrochloride 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.