Drug & supplement interaction

Bitter Orange + Darolutamide

Darolutamide brand name: Nubeqa.

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

Bitter Orange has a moderate interaction with Darolutamide. Bitter orange might increase levels of drugs metabolized by CYP3A4.

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

Bitter Orange and Darolutamide

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Darolutamide

Darolutamide falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Bitter Orange interacts with.

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 the short version: darolutamide (Nubeqa) is broken down partly by an enzyme called CYP3A4, and bitter orange can put a mild brake on that enzyme in your gut. If the breakdown slows, a bit more darolutamide could end up in your system. In theory, that could nudge up the chance of its usual side effects, like tiredness, achy joints or muscles, rash, or changes in blood pressure.

I want to keep this in perspective, though. The evidence comes from small studies using freshly squeezed bitter orange juice, and the real-world impact isn't well pinned down. An occasional serving of the fruit is unlikely to cause trouble, but concentrated weight-loss or energy supplements are a different story. Before adding any bitter orange product, run it past your pharmacist or oncology team 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

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, 877 moderate, 71 minor known drug interactions in our database — the Darolutamide one above is one of them. If you take anything else, check it against the full list below.

Major 10 Moderate 877 Minor 71 No known interaction 1,872 (incl. Darolutamide)
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 Darolutamide

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Darolutamide page lists 144 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 103 moderate · 38 minor.

From our pharmacist’s overview on the Darolutamide page

“Darolutamide (Nubeqa) treats prostate cancer, and supplements deserve real caution alongside it, because most of those listed here can change how much of the drug stays in your blood. Nearly all act on CYP3A4, the liver enzyme that breaks darolutamide down, or on the transport proteins that move it through cells.”

Reviewed by 2 · Jul 18, 2026

Open the Darolutamide 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 Darolutamide 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 Darolutamide 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%

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

29 days ago today
Medication Darolutamide
Top half

#1,403 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 Darolutamide

What Is Darolutamide Used For?

Brand name: Nubeqa

Nubeqa (darolutamide) is approved to treat two forms of advanced prostate cancer in adults. The first is non-metastatic castration-resistant prostate cancer (nmCRPC) — prostate cancer that keeps growing despite hormone-lowering treatment and has not yet spread to other parts of the body. The second is metastatic castration-sensitive prostate cancer (mCSPC) — prostate cancer that has spread but still responds to hormone-lowering therapy.

For mCSPC, Nubeqa can be used on its own or in combination with docetaxel (a chemotherapy medicine). In all cases, patients also receive a hormone-lowering medicine called a GnRH agonist or antagonist, or have already had surgical removal of the testicles.

See full Darolutamide 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
877Moderate
71Minor
1,871No known interaction
10 Major 877 Moderate 71 Minor 1,871 No interaction
Major

10 interactions

Moderate

877 interactions

Showing 60 of 877 moderate interactions — see all 877 on the Bitter Orange page.

Minor

71 interactions

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

No interaction 1,871 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 1,871 medications checked with no known interaction — see the full Bitter Orange list.

See the full Bitter Orange interactions page
See every supplement checked against Darolutamide, 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 Darolutamide supplement interactions › Every supplement checked against Darolutamide, ranked by severity Darolutamide 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 Darolutamide Together: Common Questions

Can you take Bitter Orange with Darolutamide?
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 Bitter Orange and Darolutamide 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 Darolutamide 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.