Drug & supplement interaction

Bitter Orange + Flecainide

Flecainide brand name: Tambocor.

Moderate Interaction
The bottom line Moderate

Flecainide 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 Flecainide

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. Flecainide 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 Flecainide

Flecainide 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 concern with pairing bitter orange and flecainide. Flecainide is a powerful heart rhythm medicine, and it can stretch out part of your heart's electrical cycle (the QT interval). Bitter orange contains synephrine, a stimulant that's a bit like adrenaline and can nudge your heart rate and blood pressure up. Stacking the two could, in theory, add stress to your heart's rhythm and raise the risk of a dangerous irregular heartbeat.

Honestly, this is mostly theoretical, based on a single case report where bitter orange plus caffeine seemed to prolong QT. Still, since flecainide is a serious rhythm drug with little room for error, I'd play it safe. Please check with your pharmacist or doctor before using any bitter orange or stimulant supplement.

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

Flecainide 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 situation with bitter orange and your flecainide. Your body clears flecainide mainly through a liver enzyme called CYP2D6. Lab studies suggest one piece of bitter orange (octopamine) can weakly block that enzyme. In theory, blocking it could let flecainide build up a little higher than usual.

I want to be honest about how shaky this is. This came from test-tube research only and has never actually been seen in real people, so the concern is mostly theoretical. That said, flecainide is a heart-rhythm drug with a narrow safety window, and bitter orange itself is a stimulant that can nudge up heart rate and blood pressure. That combination is reason enough to check with your pharmacist or doctor before adding it.

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 Flecainide 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 Bitter Orange

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

From our Q&A

Questions About Bitter Orange or Flecainide

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

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Flecainide page lists 86 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: 7 major · 61 moderate · 18 minor.

From our pharmacist’s overview on the Flecainide page

“Flecainide (Tambocor) exists to control serious heart rhythm problems, so anything that disturbs the rhythm it protects deserves genuine caution. Six of the seven major-rated entries among the 86 supplements and herbs on file, grapefruit in large amounts included, can prolong the QT interval, the heart's electrical reset time, adding t…”

Reviewed by 2 · Jul 18, 2026

Open the Flecainide 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 Flecainide 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 Flecainide 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%

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

29 days ago today
Medication Flecainide
Top half

#888 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 Flecainide

What Is Flecainide Used For?

Brand name: Tambocor

Flecainide Acetate tablets are used to prevent episodes of certain abnormal heart rhythms. In patients without structural heart disease, it is approved to prevent paroxysmal supraventricular tachycardia (PSVT — episodes of rapid heart rate starting above the ventricles) and paroxysmal atrial fibrillation/flutter (PAF — intermittent episodes of irregular, rapid heart rhythm in the upper chambers), when these cause disabling symptoms.

Flecainide Acetate tablets are also used to prevent life-threatening ventricular arrhythmias — dangerous rapid rhythms starting in the lower chambers of the heart, such as sustained ventricular tachycardia. It is not recommended for less serious ventricular arrhythmias, for patients with a recent heart attack, or for chronic (ongoing, persistent) atrial fibrillation.

See full Flecainide 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
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
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 Bitter Orange and Flecainide Together: Common Questions

Can you take Bitter Orange with Flecainide?
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 Flecainide?
Flecainide 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 Flecainide 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 Flecainide 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.