Drug & supplement interaction

St. John's Wort + Meperidine, Promethazine

Meperidine, Promethazine brand names: Meprozine, Mepergan.

Moderate Interaction
The bottom line Moderate

Meperidine, Promethazine falls into 2 drug categories that St. John's Wort can interact with; the most serious is rated moderate. Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

St. John's Wort and Meperidine, Promethazine

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

Why Are There 2 Interactions?

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

Moderate

SEROTONERGIC DRUGS

1 of 2

Why this applies to Meperidine, Promethazine

Meperidine, Promethazine falls under SEROTONERGIC DRUGS — the group St. John's Wort interacts with.

Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.
Concomitant use of serotonergic drugs with St. John's wort can lead to increased adverse effects and increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstriction 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: Meprozine and Mepergan contain meperidine, an opioid that also raises serotonin activity in your body. St. John's wort can nudge serotonin levels up too. Stack the two and you may get more serotonin than your body wants. That can lead to serotonin syndrome, with symptoms like agitation, a racing heart, sweating, shivering, muscle twitching, or confusion.

I'll be straight with you: this warning is mostly theoretical, based on how both work rather than lots of real cases. But meperidine is one of the riskier opioids for this, so I wouldn't shrug it off. Please check with your pharmacist or doctor before pairing them, and don't change either one on your own.

References
  1. Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  2. Gordon JB. SSRIs and St. John's Wort: possible toxicity? Am Fam Physician 1998;57:950, 953.
  3. Beckman SE, Sommi RW, Switzer J. Consumer use of St. John's wort: A survey of effectiveness, safety, and tolerability. Pharmacotherapy 2000;20:568-74.
  4. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  5. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T
Moderate

PHOTOSENSITIZING DRUGS

2 of 2

Meperidine, Promethazine also falls under PHOTOSENSITIZING DRUGS.

Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.
St. John's wort might increase photosensitivity reactions due to its hypericin content. However, some clinical research shows that very high doses of St. John's wort are needed to produce phototoxicity in humans.
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 deal with this combo. Both St. John's wort (because of a compound called hypericin) and the promethazine in Meprozine can make your skin more sensitive to sunlight. So the worry is simply additive: stacking them together could, in theory, make you sunburn faster or break out in a rash after time outdoors. This isn't about either drug building up in your blood, it's just two things that both nudge your skin toward sun sensitivity.

The good news is that this is theoretical, based on how these ingredients behave rather than on strong patient studies. In fact, research suggests you'd need very high doses of St. John's wort to cause real phototoxicity. Still, it's smart to use sunscreen and cover up, and to check with your pharmacist or doctor before combining them.

References
  1. Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  2. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
  3. Schempp CM, Muller K, Winghofer B, et al. Single-dose and steady-state administration of Hypericum perfotatum extract (St. John's wort) does not influence skin sensitivity to UV radiation, visible light, and solar-stimulated radiation. Arch Dermatol 2001;
  4. Bernd A, Ramirez-Bosca A, Kippenberger S, and et al. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol 1999;2(69):218-221.
  5. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. 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

St. John's Wort Also Interacts With Other Medications

St. John's Wort has 755 major, 387 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.

Taking anything else?

Check Another of Your Medications Against St. John's Wort

Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.

From our Q&A

Questions About St. John's Wort or Meperidine, Promethazine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers St. John's Wort or Meperidine, Promethazine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Meperidine, Promethazine

This page covers St. John's Wort 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 St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Meperidine, Promethazine too, on top of St. John's Wort — 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 St. John's Wort 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 St. John's Wort
Top 25%

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

29 days ago today
Medication Meperidine, Promethazine
Top 10%

#273 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 St. John's Wort

What is St. John's Wort?

St. John's Wort
  • Mild to moderate depression
  • Anxiety and stress
  • Sleep problems
  • Menopausal symptoms
  • Wound healing (topical)

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.

Read the full St. John's Wort monograph & all interactions
Keep checking

Other Drugs & St. John's Wort

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

755Major
387Moderate
0Minor
1,687No known interaction
Major

755 interactions

Showing 60 of 755 major interactions — see all 755 on the St. John's Wort page.

Moderate

387 interactions

Showing 60 of 387 moderate interactions — see all 387 on the St. John's Wort page.

No interaction 1,687 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking St. John's Wort and Meperidine, Promethazine Together: Common Questions

Can you take St. John's Wort with Meperidine, Promethazine?
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.
Why are there 2 interactions listed for St. John's Wort and Meperidine, Promethazine?
Meperidine, Promethazine belongs to more than one drug category, and St. John's Wort 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 St. John's Wort and Meperidine, Promethazine 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

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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.