Drug & supplement interaction

Phenylalanine + Safinamide Mesylate

Safinamide Mesylate brand name: Xadago.

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

Phenylalanine has a moderate interaction with Safinamide Mesylate. Theoretically, concomitant use of L-phenylalanine and non-selective MAOIs might increase the risk of hypertensive crisis.

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

Phenylalanine and Safinamide Mesylate

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

Moderate

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Why this applies to Safinamide Mesylate

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

Theoretically, concomitant use of L-phenylalanine and non-selective MAOIs might increase the risk of hypertensive crisis.
L-phenylalanine is metabolized to tyrosine. Some evidence suggests that L-phenylalanine, given with the non-selective MAOI pargyline, might prevent the elimination of tyramine, increasing the risk of hypertensive crisis. However, this was not reported in a small number of patients when using L-phenylalanine with the partially selective MAO-B inhibitor, selegiline.
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 thinking behind pairing phenylalanine with safinamide (Xadago). Your body turns phenylalanine into tyrosine, and tyrosine can become tyramine, a compound that nudges blood pressure up. Safinamide blocks an enzyme (MAO-B) that helps clear these substances, so in theory loading up on phenylalanine could let tyramine build and trigger a blood pressure spike (a hypertensive crisis), with symptoms like a pounding headache, racing heart, or flushing.

I want to be honest about the evidence: this is mostly theoretical and comes from lab work and an older non-selective MAOI. Safinamide is more selective, and a related selective drug (selegiline) didn't show this problem in a small study. Still, since it touches blood pressure, run any phenylalanine supplement past your pharmacist or doctor first before adding it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Silkaitis RP, Mosnaim AD. Pathways linking L-phenylalanine and 2-phenylethylamine with p-tyramine in rabbit brain. Brain Res 1976;114:105-15.
  2. Lehmann WD, Theobald N, Fischer R, Heinrich HC. Stereospecificity of phenylalanine plasma kinetics and hydroxylation in man following oral application of a stable isotope-labelled pseudo-racemic mixture of L- and D-phenylalanine. Clin Chim Acta 1983;128 PubMed
  3. Birkmayer W, Riederer P, Linauer W, Knoll J. L-deprenyl plus L-phenylalanine in the treatment of depression. J Neural Transm 1984;59:81-7. PubMed
  4. Baker GB, Bornstein RA, Rouget AC, et al. Phenylethylaminergic mechanisms in attention-deficit disorder. Biol Psychiatry 1991;29:15-22.. 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

Phenylalanine Also Interacts With Other Medications

Phenylalanine has 5 major, 10 moderate 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 5 Moderate 10 No known interaction 2,815 (incl. Safinamide Mesylate)
Taking anything else?

Check Another of Your Medications Against Phenylalanine

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

Everything else you take

See Every Supplement That Interacts With Safinamide Mesylate

This page covers Phenylalanine 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), Bitter Orange (major), Brewer's Yeast (major) and Cowhage (major).

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

Open the Safinamide Mesylate interaction page

One more smart check

Taking Phenylalanine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,990 real supplement products containing Phenylalanine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phenylalanine. Your product may carry other ingredients that interact with Safinamide Mesylate too, on top of Phenylalanine — 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 Phenylalanine 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 Phenylalanine
Top 10%

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

29 days ago today
Medication Safinamide Mesylate
Top half

#863 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 Phenylalanine

What is Phenylalanine?

  • Depression and mood
  • Skin condition vitiligo
  • Pain conditions
  • Attention and focus
  • Appetite control

Phenylalanine is an essential amino acid the body uses to make brain chemicals like dopamine and norepinephrine. Some people take it for mood, vitiligo, or pain, but the evidence is mostly limited or mixed. People with the genetic condition PKU must strictly avoid it.

Read the full Phenylalanine 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 & Phenylalanine

Browse every other medication we’ve checked against Phenylalanine — both the ones with a known interaction and the ones without. Select any drug for the full detail.

5Major
10Moderate
0Minor
2,814No known interaction
5 Major 10 Moderate 2,814 No interaction
Major

5 interactions

Moderate

10 interactions

No interaction 2,814 drugs checked — show the list

We also checked Phenylalanine against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,814 medications checked with no known interaction — see the full Phenylalanine list.

See the full Phenylalanine 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
Phenylalanine 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 Phenylalanine and Safinamide Mesylate Together: Common Questions

Can you take Phenylalanine with Safinamide Mesylate?
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 Phenylalanine and Safinamide Mesylate 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 Safinamide Mesylate and Phenylalanine?

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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.