Drug & supplement interaction

Methylsynephrine + Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine brand name: Actifed Allergy.

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

Methylsynephrine has a moderate interaction with Diphenhydramine, Pseudoephedrine. Methylsynephrine has cardiac stimulant effects.

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

Methylsynephrine and Diphenhydramine, Pseudoephedrine

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

Moderate

STIMULANT DRUGS

Why this applies to Diphenhydramine, Pseudoephedrine

Diphenhydramine, Pseudoephedrine falls under STIMULANT DRUGS — the group Methylsynephrine interacts with.

Methylsynephrine has cardiac stimulant effects. Theoretically, taking methylsynephrine with other stimulant drugs might increase the risk of hypertension and adverse cardiovascular effects.
Some stimulant drugs include amphetamine, caffeine, diethylpropion (Tenuate), methylphenidate, phentermine (Ionamin), pseudoephedrine (Sudafed, others), and many others.
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 thing to watch with this combo. Your Actifed Allergy product contains pseudoephedrine, which is itself a stimulant decongestant. It already nudges up your heart rate and blood pressure. Methylsynephrine is a separate stimulant that pushes in the same direction, so stacking the two could add up. The concern is more pounding heartbeat, jitteriness, anxiety, trouble sleeping, and most importantly higher blood pressure.

This is a theoretical caution based on how both ingredients work, not strong human studies, so don't panic if you've taken them together. Still, methylsynephrine isn't a legal or proven supplement, and the safest move is to avoid it. Please check with your pharmacist or doctor, especially if you have any heart or blood pressure issues.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pawar RS, Grundel E. Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs). Drug Test Anal 2017;9:500-517. PubMed
  2. Cohen PA, Avula B, Venhuis B, Travis JC, Wang YH, Khan IA. Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA. Drug Test Anal. 2017;9(1):135-142. 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

Methylsynephrine Also Interacts With Other Medications

Methylsynephrine has 190 moderate known drug interactions in our database — the Diphenhydramine, Pseudoephedrine one above is one of them. If you take anything else, check it against the full list below.

Moderate 190 No known interaction 2,640 (incl. Diphenhydramine, Pseudoephedrine)
Taking anything else?

Check Another of Your Medications Against Methylsynephrine

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

Everything else you take

See Every Supplement That Interacts With Diphenhydramine, Pseudoephedrine

This page covers Methylsynephrine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diphenhydramine, Pseudoephedrine page lists 185 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Ephedra (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 13 major · 150 moderate · 22 minor.

From our pharmacist’s overview on the Diphenhydramine, Pseudoephedrine page

“This medicine pulls in two directions at once, which is exactly why the supplement list for diphenhydramine and pseudoephedrine (Actifed Allergy) is not one to skim. The antihistamine half is sedating, so anything else that slows the brain deepens drowsiness; beer, wine, and kava all carry major ratings, with alcohol the best documented.”

Reviewed by 2 · Jul 18, 2026

Open the Diphenhydramine, Pseudoephedrine interaction page

One more smart check

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

We hold 55 real supplement products containing Methylsynephrine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Methylsynephrine. Your product may carry other ingredients that interact with Diphenhydramine, Pseudoephedrine too, on top of Methylsynephrine — 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 Methylsynephrine and Diphenhydramine, Pseudoephedrine 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 Methylsynephrine
Top 25%

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

29 days ago today
Medication Diphenhydramine, Pseudoephedrine
Steady interest

#1,611 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 Methylsynephrine

What is Methylsynephrine?

  • Weight loss and fat burning
  • Boosting energy
  • Athletic and workout performance
  • Appetite control

Methylsynephrine (also called oxilofrine) is a synthetic stimulant sometimes added to weight-loss and pre-workout products, but it is not a legal or approved dietary ingredient in the United States. It has been linked to serious heart and blood pressure problems, and there is no good evidence it is safe or effective for these uses, so it is best avoided.

Read the full Methylsynephrine monograph & all interactions
Keep checking

Other Drugs & Methylsynephrine

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

0Major
190Moderate
0Minor
2,639No known interaction
190 Moderate 2,639 No interaction
Moderate

190 interactions

Showing 60 of 190 moderate interactions — see all 190 on the Methylsynephrine page.

No interaction 2,639 drugs checked — show the list

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

Showing the 60 most looked-up of 2,639 medications checked with no known interaction — see the full Methylsynephrine list.

See the full Methylsynephrine interactions page
See every supplement checked against Diphenhydramine, Pseudoephedrine, 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
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Pharmacist Counseling Corner

Taking Methylsynephrine and Diphenhydramine, Pseudoephedrine Together: Common Questions

Can you take Methylsynephrine with Diphenhydramine, Pseudoephedrine?
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 Methylsynephrine and Diphenhydramine, Pseudoephedrine 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 Diphenhydramine, Pseudoephedrine and Methylsynephrine?

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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.