Drug & supplement interaction

Bitter Orange + Doxepin

Doxepin brand names: Sinequan, Doxepin, Zonalon.

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

Doxepin falls into 2 drug categories that Bitter Orange can interact with; the most serious is rated moderate. Theoretically, bitter orange might have an additive effect when combined with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.

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

Bitter Orange and Doxepin

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

Why Are There 2 Interactions?

Bitter Orange interacts with whole categories of medication. Doxepin falls into 2 of those categories, so it can interact with Bitter Orange in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

QT INTERVAL-PROLONGING DRUGS

1 of 2

Why this applies to Doxepin

Doxepin falls under QT INTERVAL-PROLONGING DRUGS — the group Bitter Orange interacts with.

Theoretically, bitter orange might have an additive effect when combined with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
One case report suggests that taking bitter orange in combination with other stimulants such as caffeine might prolong the QT interval in some patients.
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 simple version: doxepin is a tricyclic antidepressant, and at higher doses these medicines can stretch out part of your heart's electrical rhythm (what we call the QT interval). Bitter orange contains synephrine, a stimulant that bumps up heart rate and blood pressure and may also nudge that same rhythm. Put them together and, in theory, the effects could stack and raise the chance of an irregular heartbeat.

I want to be honest about how strong this concern is. It rests on anecdotal reports, including one case where bitter orange plus caffeine seemed to prolong QT. It's not proven, but since both can affect heart rhythm, I'd play it safe. Please check with your pharmacist or doctor before adding any bitter orange or weight-loss/energy supplement while you take doxepin.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc 2004;79:1059-62.. PubMed
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 2

Doxepin also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes. This effect has not been reported in humans.
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 gist for your sleep dose of doxepin (Silenor). Your body uses a liver enzyme called CYP2D6 to help clear doxepin out. Lab studies suggest one piece of bitter orange (octopamine) might gently slow that enzyme down. If that happened, a little more doxepin could linger in your system, which in theory might mean more grogginess, dry mouth, dizziness, or a stronger morning hangover feeling.

That said, I want to be honest about how thin the evidence is. This was only seen in test tubes, never shown in real people, and it's rated a minor interaction. There's also the separate point that bitter orange is a stimulant, which works against a sleep aid. I wouldn't lose sleep over this, but do mention both to your pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu Y, Santillo MF. Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements. Drug Test Anal. 2016;8(3-4):307-10. 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

Bitter Orange Also Interacts With Other Medications

Bitter Orange has 10 major, 875 moderate, 71 minor known drug interactions in our database — the Doxepin one above is among them. If you take anything else, check it against the full list below.

Major 10 Moderate 875 Minor 71 No known interaction 1,874 (incl. Doxepin)
Taking anything else?

Check Another of Your Medications Against Bitter Orange

Covers the 2,830 medications we’ve checked against Bitter Orange. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Doxepin

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Doxepin page lists 186 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), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 15 major · 145 moderate · 26 minor.

From our pharmacist’s overview on the Doxepin page

“Doxepin is a sedating tricyclic prescribed for depression, anxiety, and often sleep itself, and the people taking it tend to shop the same shelf where the trouble sits. Of the 186 supplements on file, 78 deepen its drowsiness, with alcohol (beer and wine carry major, well-documented ratings) and kava the clearest examples, and I would…”

Reviewed by 2 · Jul 18, 2026

Open the Doxepin interaction page

One more smart check

Taking Bitter Orange as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,000 real supplement products containing Bitter Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bitter Orange. Your product may carry other ingredients that interact with Doxepin too, on top of Bitter Orange — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Bitter Orange and Doxepin 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 Bitter Orange
Top 25%

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

29 days ago today
Medication Doxepin
Top half

#1,145 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 Bitter Orange

What is Bitter Orange?

Bitter Orange
  • Weight loss
  • Athletic performance and energy
  • Digestive upset
  • Appetite control
  • Aromatherapy for stress (neroli oil)

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance is limited, and because it can raise heart rate and blood pressure, people with heart problems, high blood pressure, or who are pregnant should avoid it. Talk to your pharmacist or doctor before using it, especially if you take other stimulants.

Read the full Bitter Orange monograph & all interactions
Medication

About Doxepin (Insomnia)

What Is Doxepin (Insomnia) Used For?

Brand names: Sinequan, Doxepin, Zonalon

This product is marketed to temporarily relieve occasional trouble sleeping when it's brought on by anxiety, restlessness, stress, or sensitivity to caffeine.

It is a homeopathic remedy — meaning its claims are based on traditional homeopathic practice, not accepted medical evidence, and it has not been evaluated by the FDA for effectiveness.

See full Doxepin (Insomnia) drug information
Keep checking

Other Drugs & Bitter Orange

Browse every other medication we’ve checked against Bitter Orange — both the ones with a known interaction and the ones without. Select any drug for the full detail.

10Major
875Moderate
71Minor
1,873No known interaction
10 Major 875 Moderate 71 Minor 1,873 No interaction
Major

10 interactions

Moderate

875 interactions

Showing 60 of 875 moderate interactions — see all 875 on the Bitter Orange page.

Minor

71 interactions

Showing 60 of 71 minor interactions — see all 71 on the Bitter Orange page.

No interaction 1,873 drugs checked — show the list

We also checked Bitter Orange against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,873 medications checked with no known interaction — see the full Bitter Orange list.

See the full Bitter Orange interactions page
See every supplement checked against Doxepin, 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
Bitter Orange monograph › Uses, safety, and every drug interaction in one place Doxepin supplement interactions › Every supplement checked against Doxepin, ranked by severity Doxepin (Insomnia) 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 Bitter Orange and Doxepin Together: Common Questions

Can you take Bitter Orange with Doxepin?
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 Bitter Orange and Doxepin?
Doxepin belongs to more than one drug category, and Bitter Orange 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 Bitter Orange and Doxepin 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 Doxepin and Bitter Orange?

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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.