Drug & supplement interaction

Bitter Orange + Hydrochlorothiazide, Propranolol

Hydrochlorothiazide, Propranolol brand name: Inderide.

Minor Interaction
The bottom line Minor

Bitter Orange has a minor interaction with Hydrochlorothiazide, Propranolol. Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.

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

Bitter Orange and Hydrochlorothiazide, Propranolol

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

Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Why this applies to Hydrochlorothiazide, Propranolol

Hydrochlorothiazide, Propranolol falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Bitter Orange interacts with.

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

Inderide combines a water pill (hydrochlorothiazide) with propranolol, a beta-blocker that slows your heart and lowers blood pressure. Propranolol is partly cleared by a liver enzyme called CYP2D6. In lab dishes, one ingredient in bitter orange (octopamine) weakly slowed that enzyme down. In theory, that could let a bit more propranolol build up, which might mean a slower heart rate, more tiredness, dizziness, or lightheadedness. Keep in mind this has only been seen in test tubes, never in real people, so it's rated minor.

The bigger concern is that bitter orange contains synephrine, a stimulant that can raise heart rate and blood pressure, working directly against what propranolol is trying to do. Please check with your pharmacist or doctor before combining them.

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, 876 moderate, 70 minor known drug interactions in our database — the Hydrochlorothiazide, Propranolol one above is one of 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.

Everything else you take

See Every Supplement That Interacts With Hydrochlorothiazide, Propranolol

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrochlorothiazide, Propranolol page lists 324 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Asarabacca (major) and Dolomite (major).

By severity: 11 major · 273 moderate · 40 minor.

From our pharmacist’s overview on the Hydrochlorothiazide, Propranolol page

“Inderide combines hydrochlorothiazide, a water pill, with propranolol, a beta blocker, so a supplement that also lowers blood pressure or pulls potassium out of the body hits the drug on its own turf. That describes most of this list, and I'd approach it with genuine care.”

Reviewed by 2 · Jul 18, 2026

Open the Hydrochlorothiazide, Propranolol 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 Hydrochlorothiazide, Propranolol 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 Hydrochlorothiazide, Propranolol 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 Hydrochlorothiazide, Propranolol
Top half

#1,319 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
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
876Moderate
70Minor
1,873No known interaction
Major

10 interactions

Moderate

876 interactions

Showing 60 of 876 moderate interactions — see all 876 on the Bitter Orange page.

Minor

70 interactions

Showing 60 of 70 minor interactions — see all 70 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 Hydrochlorothiazide, Propranolol Together: Common Questions

Can you take Bitter Orange with Hydrochlorothiazide, Propranolol?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Bitter Orange and Hydrochlorothiazide, Propranolol interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Hydrochlorothiazide, Propranolol 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.