Drug & supplement interaction

L-tryptophan + Meperidine, Promethazine

Meperidine, Promethazine brand names: Meprozine, Mepergan.

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

Meperidine, Promethazine falls into 2 drug categories that L-tryptophan can interact with; the most serious is rated major. Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

L-tryptophan and Meperidine, Promethazine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

L-tryptophan interacts with whole categories of medication. Meperidine, Promethazine falls into 2 of those categories, so it can interact with L-tryptophan in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

CNS DEPRESSANTS

1 of 2

Why this applies to Meperidine, Promethazine

Meperidine, Promethazine falls under CNS DEPRESSANTS — the group L-tryptophan interacts with.

Theoretically, concomitant use of L-tryptophan with CNS depressants might cause additive sedative effects.
Clinical research shows that L-tryptophan can cause fatigue and drowsiness.
Severity Major Likelihood Probable Evidence B

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 thing to keep in mind: Meprozine (meperidine plus promethazine) already packs two sedating ingredients. Meperidine is a narcotic pain reliever, and promethazine is an antihistamine that makes most people very drowsy. Both slow down the brain and body. L-tryptophan can add its own sleepy, fatigued feeling on top of that, so stacking them may leave you more groggy than you'd expect.

What could show up? Heavier drowsiness, dizziness, foggy thinking, and in a worst case, slowed or shallow breathing. There's an extra wrinkle too: meperidine and serotonin-raising products together can rarely trigger serotonin-related reactions. The evidence here is modest, but the additive sedation is real enough that I'd ask your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lieberman HR, Corkin S, Spring BJ. The effects of dietary neurotransmitter precursors on human behavior. Am J Clin Nutr 1985;42:366-70. PubMed
Moderate

SEROTONERGIC DRUGS

2 of 2

Meperidine, Promethazine also falls under SEROTONERGIC DRUGS.

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 with this combo product, Meprozine or Mepergan. It contains meperidine, an opioid pain reliever, along with promethazine. Meperidine is one of the opioids that actually nudges serotonin levels upward in the brain, separate from its pain-relieving job. L-tryptophan also raises serotonin, since your body uses it as the raw material to make it. So stacking the two together could, in theory, push serotonin too high.

What that might look like: agitation, a racing heart, sweating, shivering, muscle twitching, or confusion, which together can signal serotonin syndrome. I'll be honest, this is a theoretical concern based on how the drugs work, not strong real-world data, so don't panic. Still, please run it by your pharmacist or doctor before combining them.

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 247 major, 146 moderate known drug interactions in our database — the Meperidine, Promethazine one above is among them. If you take anything else, check it against the full list below.

Major 247 Moderate 146 No known interaction 2,437 (incl. Meperidine, Promethazine)
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 Meperidine, Promethazine

This page covers L-tryptophan only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Meperidine, Promethazine page lists 207 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), Gamma-hydroxybutyrate (ghb) (major) and Henbane (major).

By severity: 10 major · 160 moderate · 37 minor.

From our pharmacist’s overview on the Meperidine, Promethazine page

“Meprozine combines meperidine, an opioid painkiller, with promethazine, a sedating antihistamine, so it already slows the brain on two fronts. I would read this list of 207 supplements and herbal ingredients with genuine care, starting with the 10 rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Meperidine, Promethazine 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 Meperidine, Promethazine 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 Meperidine, Promethazine 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

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

29 days ago today
Medication Meperidine, Promethazine
Top 25%

#365 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.

247Major
146Moderate
0Minor
2,436No known interaction
247 Major 146 Moderate 2,436 No interaction
Major

247 interactions

Showing 60 of 247 major interactions — see all 247 on the L-tryptophan page.

Moderate

146 interactions

Showing 60 of 146 moderate interactions — see all 146 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 Meperidine, Promethazine, 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 Meperidine, Promethazine supplement interactions › Every supplement checked against Meperidine, Promethazine, 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 Meperidine, Promethazine Together: Common Questions

Can you take L-tryptophan with Meperidine, Promethazine?
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.
Why are there 2 interactions listed for L-tryptophan and Meperidine, Promethazine?
Meperidine, Promethazine belongs to more than one drug category, and L-tryptophan interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the L-tryptophan and Meperidine, Promethazine 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 Meperidine, Promethazine 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.