Drug & supplement interaction

Bitter Orange + Safinamide Mesylate

Safinamide Mesylate brand name: Xadago.

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

Bitter Orange has a major interaction with Safinamide Mesylate. Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.

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

Bitter Orange and Safinamide Mesylate

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

Major

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Why this applies to Safinamide Mesylate

Safinamide Mesylate falls under MONOAMINE OXIDASE INHIBITORS (MAOIs) — the group Bitter Orange interacts with.

Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates.
Severity Major Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the concern with pairing bitter orange and Xadago (safinamide). Safinamide is an MAO-B inhibitor, meaning it slows down one of the enzymes your body uses to break down certain stimulant-like compounds. Bitter orange supplements contain synephrine (plus tyramine and octopamine), which are exactly the kinds of substances that enzyme normally helps clear out. When you block that breakdown, these stimulants can pile up.

The worry is a sharp spike in blood pressure, possibly even a dangerous hypertensive crisis, along with a racing heart, headache, or chest discomfort. To be fair, this is rated as theoretical and based on lab-type reasoning, not patient studies, so the exact risk isn't proven. But because the potential outcome is serious, I'd play it safe. Please check with your pharmacist or doctor before using any bitter orange product alongside safinamide.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pellati F, Benvenuti S, Melegari M, Firenzuoli F. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. var. amara by LC. J Pharm Biomed Anal 2002;29:1113-9. . PubMed
  2. Visentin V, Morin N, Fontana E, et al. Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases. J Pharmacol Exp Ther 2001;299:96-104.
  3. Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979;35:1283-4. 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 9 major, 876 moderate, 71 minor known drug interactions in our database — the Safinamide Mesylate one above is one of them. If you take anything else, check it against the full list below.

Major 9 Moderate 876 Minor 71 No known interaction 1,874 (incl. Safinamide Mesylate)
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 Safinamide Mesylate

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Safinamide Mesylate page lists 81 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Brewer's Yeast (major), Cowhage (major) and Fever Bark (major).

By severity: 14 major · 56 moderate · 11 minor.

Open the Safinamide Mesylate 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 Safinamide Mesylate 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 Safinamide Mesylate 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 Safinamide Mesylate
Top half

#720 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 Safinamide

What Is Safinamide Used For?

Brand name: Xadago

Xadago (safinamide) is used as an add-on treatment for adults with Parkinson's disease who are already taking levodopa/carbidopa and experiencing 'off' episodes — times when the medication wears off and Parkinson's symptoms return before the next dose is due.

Xadago is not used alone; it works only in combination with levodopa/carbidopa.

See full Safinamide 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.

9Major
876Moderate
71Minor
1,873No known interaction
9 Major 876 Moderate 71 Minor 1,873 No interaction
Major

9 interactions

Moderate

876 interactions

Showing 60 of 876 moderate interactions — see all 876 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 Safinamide Mesylate, 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 Safinamide Mesylate supplement interactions › Every supplement checked against Safinamide Mesylate, ranked by severity Safinamide 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 Safinamide Mesylate Together: Common Questions

Can you take Bitter Orange with Safinamide Mesylate?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Bitter Orange and Safinamide Mesylate interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Safinamide Mesylate 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.