Drug & supplement interaction

L-tryptophan + Dextromethorphan HBr, Phenylephrine HCl

Dextromethorphan HBr, Phenylephrine HCl brand name: Vicks Formula 44D Cough & Head Congestion Relief.

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

L-tryptophan has a moderate interaction with Dextromethorphan HBr, Phenylephrine HCl. Theoretically, combining L-tryptophan with serotonergic drugs might cause additive serotonergic effects.

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

L-tryptophan and Dextromethorphan HBr, Phenylephrine HCl

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

Moderate

SEROTONERGIC DRUGS

Why this applies to Dextromethorphan HBr, Phenylephrine HCl

Dextromethorphan HBr, Phenylephrine HCl falls under SEROTONERGIC DRUGS — the group L-tryptophan interacts with.

Theoretically, combining L-tryptophan with serotonergic drugs might cause additive serotonergic effects.
L-tryptophan is a precursor to serotonin. Theoretically, combining serotonergic drugs with L-tryptophan might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders.
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 know about this combo: the dextromethorphan in Vicks Formula 44D nudges serotonin levels up in the brain, and L-tryptophan does the same by acting as a building block for serotonin. Stack them together and you're theoretically pushing serotonin from two directions at once. That's why this gets flagged.

To be clear, this concern is theoretical, based on how these two work rather than a long list of real-world cases, so I don't want to alarm you. Still, it's worth watching for signs of too much serotonin: agitation, shakiness, sweating, a racing heart, or feeling flushed and confused. Phenylephrine can also raise blood pressure a bit on its own. If you take tryptophan regularly, just run this past your pharmacist or doctor before reaching for the cough syrup.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol 1993;31:603-30. PubMed
  2. 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

L-tryptophan Also Interacts With Other Medications

L-tryptophan has 248 major, 145 moderate known drug interactions in our database — the Dextromethorphan HBr, Phenylephrine HCl one above is one of them. If you take anything else, check it against the full list below.

Major 248 Moderate 145 No known interaction 2,437 (incl. Dextromethorphan HBr, Phenylephrine HCl)
Taking anything else?

Check Another of Your Medications Against L-tryptophan

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

Everything else you take

See Every Supplement That Interacts With Dextromethorphan HBr, Phenylephrine HCl

This page covers L-tryptophan only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dextromethorphan HBr, Phenylephrine HCl page lists 197 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 · 148 moderate · 41 minor.

From our pharmacist’s overview on the Dextromethorphan HBr, Phenylephrine HCl page

“The supplement interactions with Dextromethorphan HBr and Phenylephrine HCl (Vicks Formula 44D) deserve real respect, and the small cluster of major-rated ones should be understood before you reach for the bottle. Phenylephrine is a stimulant-type decongestant, so anything with caffeine (coffee, tea, cola nut) or ephedrine-like herbs s…”

Reviewed by 2 · Jul 18, 2026

Open the Dextromethorphan HBr, Phenylephrine HCl interaction page

One more smart check

Taking L-tryptophan as Part of a Dietary Supplement Product? Check It for Interactions

We hold 5 real supplement products containing L-tryptophan, each one broken down to its full ingredient list — and combination products often carry several ingredients besides L-tryptophan. Your product may carry other ingredients that interact with Dextromethorphan HBr, Phenylephrine HCl too, on top of L-tryptophan — 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 L-tryptophan and Dextromethorphan HBr, Phenylephrine HCl 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 L-tryptophan
Steady interest

#1,030 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Dextromethorphan HBr, Phenylephrine HCl
Steady interest

#2,577 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 L-tryptophan

What is L-tryptophan?

L-tryptophan
  • Sleep problems
  • Low mood and depression
  • Anxiety
  • Premenstrual symptoms
  • Appetite and food cravings

L-tryptophan is an essential amino acid the body uses to make serotonin and melatonin, and people take it to support sleep and mood. The evidence for supplement use is limited and mixed, and there are real safety concerns, so talk to a pharmacist or doctor before trying it.

Read the full L-tryptophan monograph & all interactions
Keep checking

Other Drugs & L-tryptophan

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

248Major
145Moderate
0Minor
2,436No known interaction
248 Major 145 Moderate 2,436 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the L-tryptophan page.

Moderate

145 interactions

Showing 60 of 145 moderate interactions — see all 145 on the L-tryptophan page.

No interaction 2,436 drugs checked — show the list

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

Showing the 60 most looked-up of 2,436 medications checked with no known interaction — see the full L-tryptophan list.

See the full L-tryptophan interactions page
See every supplement checked against Dextromethorphan HBr, Phenylephrine HCl, 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
L-tryptophan monograph › Uses, safety, and every drug interaction in one place Dextromethorphan HBr, Phenylephrine HCl supplement interactions › Every supplement checked against Dextromethorphan HBr, Phenylephrine HCl, 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 L-tryptophan and Dextromethorphan HBr, Phenylephrine HCl Together: Common Questions

Can you take L-tryptophan with Dextromethorphan HBr, Phenylephrine HCl?
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 L-tryptophan and Dextromethorphan HBr, Phenylephrine HCl 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 HBr, Phenylephrine HCl and L-tryptophan?

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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.