Drug & supplement interaction

Bitter Orange + Tamoxifen Citrate

Tamoxifen Citrate brand names: Nolvadex, Soltamox.

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

Tamoxifen Citrate falls into 3 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
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Bitter Orange and Tamoxifen Citrate

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Bitter Orange interacts with whole categories of medication. Tamoxifen Citrate falls into 3 of those categories, so it can interact with Bitter Orange in 3 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 3

Why this applies to Tamoxifen Citrate

Tamoxifen Citrate 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 gist: tamoxifen can, in some people, affect the heart's electrical timing (what we call the QT interval). Bitter orange contains synephrine, a stimulant that can nudge up your heart rate and blood pressure, and there's a thought that the two together could add up and slightly raise the chance of an irregular heartbeat.

I want to be honest about how thin the evidence is here. This is mostly theoretical, backed by a single case report where bitter orange was mixed with other stimulants like caffeine. It's not a well-documented, common problem. Still, since tamoxifen is a serious medication and bitter orange supplements aren't proven to do much, I'd run it by your pharmacist or doctor before combining them, especially if you have any heart history.

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
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Tamoxifen Citrate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Bitter orange might increase levels of drugs metabolized by CYP3A4.
Small clinical studies suggest that single or multiple doses of freshly squeezed bitter orange juice 200-240 mL can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. However, the extent of the effect of bitter orange on CYP3A4-mediated drug interactions is unknown. Some evidence suggests that bitter orange selectively inhibits intestinal CYP3A4, but not hepatic CYP3A4. Its effect on P-glycoprotein, which strongly overlaps with CYP3A4 interactions, is unclear. One small clinical study shows that drinking 8 ounces of freshly squeezed bitter orange juice has no effect on cyclosporine, which seems to be more dependent on hepatic CYP3A4 and P-glycoprotein than intestinal CYP3A4.
Severity Moderate Likelihood Possible Evidence B

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 a wrinkle worth knowing about: tamoxifen is actually a prodrug. Your body has to convert it into its active form (called endoxifen) before it can do its job against breast cancer. That activation leans mostly on a different enzyme called CYP2D6, not CYP3A4, which is the enzyme bitter orange may slow down.

So while bitter orange could nudge tamoxifen's blood levels a bit by blocking gut CYP3A4, the real-world effect on how well your treatment works isn't clear, and the evidence here is on the weaker side. Food-sized amounts of bitter orange are unlikely to matter much; concentrated weight-loss or energy supplements are the bigger question. Given how important this medication is, please run any bitter orange supplement past your oncologist or pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther 2001;69:14-23. PubMed
  2. Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics. J Clin Pharmacol 2002;42:1165-70. PubMed
  3. Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
  4. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. PubMed
  5. Abdelkawy KS, Donia AM, Turner RB, Elbarbry F. Effects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects. Drugs R D. 2016 Sep;16(3):271-278. PubMed
Minor

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

3 of 3

Tamoxifen Citrate 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 something worth knowing about tamoxifen: it's actually a prodrug. Your body has to switch it on, mainly using an enzyme called CYP2D6, which turns tamoxifen into its active form (endoxifen). That active form is what does the real work against breast cancer.

Lab studies suggest a compound in bitter orange can weakly block CYP2D6. In theory, slowing that enzyme could mean less tamoxifen gets activated, which could make it work less well. That said, this comes only from test-tube research and hasn't been shown in real people, so the concern is mostly hypothetical. Because tamoxifen matters so much, I'd still play it safe and check with your oncologist or pharmacist before adding any bitter orange supplement.

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 Tamoxifen Citrate 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. Tamoxifen Citrate)
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 Tamoxifen Citrate

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 Tamoxifen Citrate, 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 Tamoxifen Citrate

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tamoxifen Citrate page lists 210 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), Beer (major) and Cesium (major).

By severity: 11 major · 166 moderate · 33 minor.

From our pharmacist’s overview on the Tamoxifen Citrate page

“Tamoxifen (Nolvadex, Soltamox) often stands between a breast cancer patient and a recurrence, so the stakes on this page run higher than usual. Eleven of the 210 supplements and herbs on file carry a major rating, and those eleven deserve your attention ahead of everything else.”

Reviewed by 2 · Jul 18, 2026

Open the Tamoxifen Citrate 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 Tamoxifen Citrate 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 Tamoxifen Citrate 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%

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

29 days ago today
Medication Tamoxifen Citrate
Top 10%

#256 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 Tamoxifen

What Is Tamoxifen Used For?

Brand names: Nolvadex, Soltamox

Tamoxifen is used to treat estrogen receptor-positive metastatic breast cancer in both women and men, and as follow-up (adjuvant) therapy after surgery for early-stage breast cancer in women. It also reduces the occurrence of cancer in the opposite breast when used as adjuvant therapy.

In women with ductal carcinoma in situ (DCIS — an early, non-invasive breast change) following surgery and radiation, tamoxifen lowers the risk of developing invasive breast cancer. It is also approved to reduce the risk of breast cancer in women who are at high risk but have not yet been diagnosed. Both Tamoxifen Citrate tablets and Soltamox oral solution share these indications.

See full Tamoxifen 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 Tamoxifen Citrate, 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 Tamoxifen Citrate supplement interactions › Every supplement checked against Tamoxifen Citrate, ranked by severity Tamoxifen 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 Tamoxifen Citrate Together: Common Questions

Can you take Bitter Orange with Tamoxifen Citrate?
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 3 interactions listed for Bitter Orange and Tamoxifen Citrate?
Tamoxifen Citrate 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 Tamoxifen Citrate 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 Tamoxifen Citrate 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.