Drug & supplement interaction

Lithium + 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 Lithium can interact with; the most serious is rated major. Theoretically, taking lithium supplements with serotonergic drugs might both mask and increase the risk of serotonin syndrome.

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

Lithium and Meperidine, Promethazine

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

Why Are There 2 Interactions?

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

Major

SEROTONERGIC DRUGS

1 of 2

Why this applies to Meperidine, Promethazine

Meperidine, Promethazine falls under SEROTONERGIC DRUGS — the group Lithium interacts with.

Theoretically, taking lithium supplements with serotonergic drugs might both mask and increase the risk of serotonin syndrome.
In a case report, a 67-year-old female with depression and bipolar disorder using lithium in combination with selective serotonin reuptake inhibitors (SSRIs) and other medications developed serotonin syndrome with symptoms of deep tendon hyperreflexia, muscle rigidity, tremor, and hyperthermia. However, agitation, one classical symptom of serotonin syndrome, was lacking. This was thought to be due to masking by lithium toxicity. Lithium can increase serotonin levels, thus, combining serotonergic drugs with lithium might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
Severity Major Likelihood Probable Evidence D

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

This combo medicine pairs meperidine (Demerol, an opioid pain reliever) with promethazine (an antihistamine for nausea). The piece that matters here is meperidine, because it nudges serotonin levels up in the brain. Lithium can do the same thing. Stacking two serotonin-raising agents may, in theory, push you toward serotonin syndrome, which can show up as tremor, muscle stiffness, overactive reflexes, sweating, fever, fast heartbeat, and confusion.

This warning is based on pharmacology and a single case report, not strong studies, so the real risk is uncertain, especially with the tiny amounts in over-the-counter lithium orotate. Still, both lithium and meperidine carry their own serious risks, so please check with your pharmacist or doctor before combining them. Don't start or stop anything on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  3. Landa E, Wagner S, Makkar A, Liu A, Jung D. An atypical presentation of serotonin syndrome. Cureus. 2021;13(2):e13377. PubMed
Moderate

PHENOTHIAZINES

2 of 2

Meperidine, Promethazine also falls under PHENOTHIAZINES.

Theoretically, taking lithium supplements with phenothiazines might decrease the levels and clinical effects of phenothiazines.
Concomitant use of lithium with phenothiazines might reduce lithium concentrations. Lithium might also reduce phenothiazine concentrations, making the pharmacokinetic effect unpredictable. It is unclear if these interactions would occur with the smaller doses found in lithium supplements.
Severity Moderate Likelihood Probable Evidence D

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

Your medicine combines meperidine (a pain reliever) with promethazine, which belongs to a group called phenothiazines. On paper, mixing lithium with a phenothiazine like promethazine could push both drug levels around in unpredictable ways. Lithium might lower the promethazine level a bit, which could mean a little less of its calming or anti-nausea effect, and the two may nudge each other's levels in either direction.

Here's the honest part: this concern is theoretical, based on how the drugs work rather than strong patient studies. It's also unclear whether the small amounts in lithium supplements (like lithium orotate) would matter at all. Still, since prescription lithium and combos like this can be tricky, please run it by your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Martindale W. Martindale the Extra Pharmacopoeia. Pharmaceutical Press, 1999.
  2. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

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

Lithium Also Interacts With Other Medications

Lithium has 258 major, 256 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 258 Moderate 256 No known interaction 2,316 (incl. Meperidine, Promethazine)
Taking anything else?

Check Another of Your Medications Against Lithium

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

From our Q&A

Questions About Lithium 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 Lithium 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 Lithium 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 Lithium as Part of a Dietary Supplement Product? Check It for Interactions

We hold 330 real supplement products containing Lithium, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lithium. Your product may carry other ingredients that interact with Meperidine, Promethazine too, on top of Lithium — 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 Lithium 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 Lithium
Top 25%

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

29 days ago today
Medication Meperidine, Promethazine
Top 25%

#640 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 Lithium

What is Lithium?

Lithium
  • Mood support
  • Bipolar disorder (prescription)
  • Healthy mental function
  • Irritability or stress
  • Sleep support

Lithium is a naturally occurring metal that, in prescription form (lithium carbonate or citrate), is an FDA-approved, well-proven treatment for bipolar disorder. Low-dose supplement forms like lithium orotate are sold for mood support, but there is very little reliable evidence that they work, and even small amounts of lithium can be risky for some people. Always talk to a pharmacist or doctor before taking any lithium product.

Read the full Lithium monograph & all interactions
Keep checking

Other Drugs & Lithium

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

258Major
256Moderate
0Minor
2,315No known interaction
258 Major 256 Moderate 2,315 No interaction
Major

258 interactions

Showing 60 of 258 major interactions — see all 258 on the Lithium page.

Moderate

256 interactions

Showing 60 of 256 moderate interactions — see all 256 on the Lithium page.

No interaction 2,315 drugs checked — show the list

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

Showing the 60 most looked-up of 2,315 medications checked with no known interaction — see the full Lithium list.

See the full Lithium 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
Lithium 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 Lithium and Meperidine, Promethazine Together: Common Questions

Can you take Lithium 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 Lithium and Meperidine, Promethazine?
Meperidine, Promethazine belongs to more than one drug category, and Lithium 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 Lithium 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 Lithium?

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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.