Drug & supplement interaction

Same + Dextromethorphan, Pseudoephedrine, Triprolidine

Dextromethorphan, Pseudoephedrine, Triprolidine brand name: Actifed DM.

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

Same has a moderate interaction with Dextromethorphan, Pseudoephedrine, Triprolidine. Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.

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

Same and Dextromethorphan, Pseudoephedrine, Triprolidine

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

Moderate

SEROTONERGIC DRUGS

Why this applies to Dextromethorphan, Pseudoephedrine, Triprolidine

Dextromethorphan, Pseudoephedrine, Triprolidine falls under SEROTONERGIC DRUGS — the group Same interacts with.

Taking SAMe with serotonergic drugs might increase the risk of serotonin syndrome and other serotonergic side effects.
SAMe has serotonergic effects. Theoretically, combining serotonergic drugs with SAMe might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. In one case report, SAMe 100 mg intramuscularly was given daily with clomipramine (Anafranil) 25 mg per day. When the clomipramine dose was increased to 75 mg per day the patient experienced serotonin syndrome about 48-72 hours later, requiring hospitalization.
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

Actifed DM contains dextromethorphan, the cough suppressant, and dextromethorphan has its own serotonin-boosting activity. SAM-e also nudges serotonin upward. Stacking the two together could, in theory, raise serotonin too much, a problem called serotonin syndrome. Watch for things like agitation, a racing heart, sweating, shivering, muscle twitching, or feeling unusually jittery or confused.

I'll be honest with you: this concern is mostly theoretical and rests on weak, anecdotal reports, so for most people taking an occasional dose it's unlikely to be a big deal. Still, since both work on the same pathway, it's worth a quick chat with your pharmacist or doctor before combining them, especially if you use either one regularly.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Iruela LM, Minguez L, Merino J, Monedero G. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522. PubMed
  2. Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H. Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. Psychiatry Res 1992;44:257-62. PubMed
  3. Rosenbaum JF, Fava M, Falk WE, et al. The antidepressant potential of oral S-adenosyl-l-methionine. Acta Psychiatr Scand 1990;81:432-6. PubMed
  4. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137-52. PubMed
  5. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. 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

Same Also Interacts With Other Medications

Same has 188 moderate known drug interactions in our database — the Dextromethorphan, Pseudoephedrine, Triprolidine one above is one of them. If you take anything else, check it against the full list below.

Moderate 188 No known interaction 2,642 (incl. Dextromethorphan, Pseudoephedrine, Triprolidine)
Taking anything else?

Check Another of Your Medications Against Same

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

Everything else you take

See Every Supplement That Interacts With Dextromethorphan, Pseudoephedrine, Triprolidine

This page covers Same only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dextromethorphan, Pseudoephedrine, Triprolidine page lists 198 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Ephedra (major), Grapefruit (major), Lithium (major) and Peyote (major).

By severity: 8 major · 149 moderate · 41 minor.

From our pharmacist’s overview on the Dextromethorphan, Pseudoephedrine, Triprolidine page

“Actifed DM pairs a stimulant decongestant (pseudoephedrine) with a cough suppressant that acts on serotonin (dextromethorphan), which is why I want you reading this list with real care before adding any supplement. Eight of the 198 flagged ingredients rate major.”

Reviewed by 2 · Jul 18, 2026

Open the Dextromethorphan, Pseudoephedrine, Triprolidine interaction page

One more smart check

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

We hold 9 real supplement products containing Same, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Same. Your product may carry other ingredients that interact with Dextromethorphan, Pseudoephedrine, Triprolidine too, on top of Same — 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 Same and Dextromethorphan, Pseudoephedrine, Triprolidine 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 Same
Top 25%

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

29 days ago today
Medication Dextromethorphan, Pseudoephedrine, Triprolidine
Steady interest

#2,566 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 Same

What is Same?

Same
  • Depression
  • Osteoarthritis joint pain
  • Liver conditions
  • Fibromyalgia

SAM-e is a compound your body makes naturally that is sold as a supplement, most often for depression and osteoarthritis. Some research suggests it may help with these conditions, but the quality of evidence is mixed and more study is needed. Talk with your pharmacist or doctor before trying it, especially if you take other medicines or have bipolar disorder.

Read the full Same monograph & all interactions
Keep checking

Other Drugs & Same

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

0Major
188Moderate
0Minor
2,641No known interaction
188 Moderate 2,641 No interaction
Moderate

188 interactions

Showing 60 of 188 moderate interactions — see all 188 on the Same page.

No interaction 2,641 drugs checked — show the list

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

Showing the 60 most looked-up of 2,641 medications checked with no known interaction — see the full Same list.

See the full Same interactions page
See every supplement checked against Dextromethorphan, Pseudoephedrine, Triprolidine, 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
Same monograph › Uses, safety, and every drug interaction in one place Dextromethorphan, Pseudoephedrine, Triprolidine supplement interactions › Every supplement checked against Dextromethorphan, Pseudoephedrine, Triprolidine, ranked by severity 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 Same and Dextromethorphan, Pseudoephedrine, Triprolidine Together: Common Questions

Can you take Same with Dextromethorphan, Pseudoephedrine, Triprolidine?
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 Same and Dextromethorphan, Pseudoephedrine, Triprolidine 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 Dextromethorphan, Pseudoephedrine, Triprolidine and Same?

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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.