Drug & supplement interaction

Fever Bark + Diphenhydramine

Diphenhydramine brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, and others.

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

Fever Bark has a moderate interaction with Diphenhydramine. Theoretically, CYP2D6 inhibitors might increase the levels and clinical effects of yohimbine, a constituent of fever bark.

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

Fever Bark and Diphenhydramine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS

Why this applies to Diphenhydramine

Diphenhydramine falls under CYTOCHROME P450 2D6 (CYP2D6) INHIBITORS — the group Fever Bark interacts with.

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 angle to focus on with this pair. Diphenhydramine (Benadryl) doesn't just treat allergies, it also gently blocks an enzyme in your liver called CYP2D6. That same enzyme is what your body uses to break down yohimbine, one of the active alkaloids in fever bark. So in theory, taking them together could slow yohimbine's clearance and let it build up a bit more than usual.

Important to keep in mind: this is a theoretical concern based on how the chemicals behave, not proven in real patients. Still, extra yohimbine can raise blood pressure, speed up the heart, and cause jitteriness or anxiety. Since fever bark already carries potent, hard-to-dose alkaloids, I'd run this combination by your pharmacist or doctor before mixing them rather than guessing.

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

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 Diphenhydramine one above is one of 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. Diphenhydramine)
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 Diphenhydramine

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 Diphenhydramine, 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 Diphenhydramine

This page covers Fever Bark only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine page lists 147 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Henbane (major).

By severity: 9 major · 119 moderate · 19 minor.

From our pharmacist’s overview on the Diphenhydramine page

“Diphenhydramine (Benadryl, Simply Sleep) is sedating by design, and most of the 147 supplements and herbal ingredients on this list lean into that. Seventy-eight are sedating substances themselves, alcohol and kava the standouts, and stacking them can slow breathing and reflexes well beyond ordinary drowsiness.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine interaction page

How much people look this up

Where Fever Bark and Diphenhydramine 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

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

29 days ago today
Medication Diphenhydramine
Top 25%

#695 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 Diphenhydramine

What Is Diphenhydramine Used For?

Brand names: Benadryl, Dormin, Allerdryl, Valdrene, Sleep-Ettes D, Simply Sleep, Sominex, Diphenhydramine, Compoz, Sleep Aid, Benadryl cream, Benadryl spray, Dermamycin cream, Ziradryl, Nytol

Diphenhydramine temporarily relieves symptoms of hay fever, other upper respiratory allergies, and the common cold — including runny nose, sneezing, itchy or watery eyes, and itching of the nose or throat.

After Bite Xtra gel is formulated for topical use and is approved to temporarily relieve pain and itching from minor burns, minor cuts and scrapes, insect bites, minor skin irritations, and rashes from poison ivy, poison oak, and poison sumac.

See full Diphenhydramine 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
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 Diphenhydramine, 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 Diphenhydramine supplement interactions › Every supplement checked against Diphenhydramine, ranked by severity Diphenhydramine drug information › The full plain-English guide to this medication 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 Diphenhydramine Together: Common Questions

Can you take Fever Bark with Diphenhydramine?
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.
How serious is the Fever Bark and Diphenhydramine 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 Diphenhydramine 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.