Drug & supplement interaction

Tianeptine + Acetaminophen, Codeine

Acetaminophen, Codeine brand names: Tylenol w/ Codeine, Tylenol No.3.

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

Tianeptine has a moderate interaction with Acetaminophen, Codeine. Tianeptine has sedative effects; high doses may have additive effects with other CNS depressants.

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

Tianeptine and Acetaminophen, Codeine

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

Moderate

CNS DEPRESSANTS

Why this applies to Acetaminophen, Codeine

Acetaminophen, Codeine falls under CNS DEPRESSANTS — the group Tianeptine interacts with.

Tianeptine has sedative effects; high doses may have additive effects with other CNS depressants.
Higher doses of tianeptine have opioid like effects and may have additive effects with other sedative drugs. In one case report, a 42-year-old male presented with respiratory depression and aspiration pneumonia due to concomitant use of high-dose tianeptine and alprazolam.
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 concern with combining tianeptine and Tylenol with Codeine. The codeine part is an opioid pain reliever, so it already slows your breathing and makes you drowsy. Tianeptine, especially at the higher doses found in those 'gas station' products, also acts a lot like an opioid. Stack the two together and those effects can pile up. We worry most about heavy sedation and slowed, shallow breathing, which can become dangerous.

This warning is based mainly on pharmacology and a case report where someone got into trouble mixing high-dose tianeptine with a sedative, so it's not proven for every person. Still, I'd strongly urge you to talk with your doctor or pharmacist before taking these together, and please be honest about any tianeptine use.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lauhan R, Hsu A, Alam A, Beizai K. Tianeptine Abuse and Dependence: Case Report and Literature Review. Psychosomatics. 2018;59(6):547-553. PubMed
  2. Lucaj S, Leo RJ. Tianeptine Sodium: A Nootropic With Potentially Lethal Consequences. Prim Care Companion CNS Disord. 2018;20(4).
  3. Samuels BA, Nautiyal KM, Kruegel AC, et al. The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor. Neuropsychopharmacology. 2017;42(10):2052-2063. 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

Tianeptine Also Interacts With Other Medications

Tianeptine has 9 major, 267 moderate known drug interactions in our database — the Acetaminophen, Codeine one above is one of them. If you take anything else, check it against the full list below.

Major 9 Moderate 267 No known interaction 2,554 (incl. Acetaminophen, Codeine)
Taking anything else?

Check Another of Your Medications Against Tianeptine

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Codeine

This page covers Tianeptine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Codeine page lists 240 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 9 major · 191 moderate · 40 minor.

From our pharmacist’s overview on the Acetaminophen, Codeine page

“People usually take Tylenol No. 3 (acetaminophen with codeine) for short-term pain, often while still drinking wine with dinner or reaching for an herbal sleep aid.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Codeine interaction page

How much people look this up

Where Tianeptine and Acetaminophen, Codeine 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 Tianeptine
Steady interest

#1,065 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Codeine
Top 5%

#51 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 Tianeptine

What is Tianeptine?

  • Depression (prescription use in some countries)
  • Anxiety
  • Mood enhancement
  • Pain relief
  • Self-treatment of opioid withdrawal
  • Recreational euphoria

Tianeptine is a prescription antidepressant in some countries, but it is NOT approved by the FDA in the United States and is illegally sold in dietary supplements and 'gas station' products. At high doses it acts like an opioid and carries serious risks of addiction, overdose, and dangerous withdrawal. We strongly advise against using over-the-counter tianeptine products and urge anyone considering it to talk with a doctor or pharmacist first.

Read the full Tianeptine monograph & all interactions
Keep checking

Other Drugs & Tianeptine

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

9Major
267Moderate
0Minor
2,553No known interaction
9 Major 267 Moderate 2,553 No interaction
Major

9 interactions

Moderate

267 interactions

Showing 60 of 267 moderate interactions — see all 267 on the Tianeptine page.

No interaction 2,553 drugs checked — show the list

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

Showing the 60 most looked-up of 2,553 medications checked with no known interaction — see the full Tianeptine list.

See the full Tianeptine interactions page
See every supplement checked against Acetaminophen, Codeine, 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
Tianeptine monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Codeine supplement interactions › Every supplement checked against Acetaminophen, Codeine, 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 Tianeptine and Acetaminophen, Codeine Together: Common Questions

Can you take Tianeptine with Acetaminophen, Codeine?
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 Tianeptine and Acetaminophen, Codeine 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.