Drug & supplement interaction

Red Clover + Tapentadol

Tapentadol brand names: Nucynta, Nucynta ER.

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

Tapentadol falls into 2 drug categories that Red Clover can interact with; the most serious is rated minor. Theoretically, red clover might increase the levels and clinical effects of drugs metabolized by CYP2C19.

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

Red Clover and Tapentadol

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

Why Are There 2 Interactions?

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

Minor

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

1 of 2

Why this applies to Tapentadol

Tapentadol falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES — the group Red Clover interacts with.

Theoretically, red clover might increase the levels and clinical effects of drugs metabolized by CYP2C19.
In vitro evidence suggests that red clover weakly inhibits CYP2C19. This interaction has not been reported in humans.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version on pairing red clover with tapentadol. The concern on file is that red clover might weakly block an enzyme called CYP2C19, which could in theory let a drug it processes build up a bit. If that happened with tapentadol, you might notice a little more of its usual effects, like drowsiness, dizziness, nausea, or constipation.

The good news: this is mostly theory. The only evidence comes from lab dishes, not from real people, and tapentadol actually leans more on other pathways for clearance, so CYP2C19 isn't its main route. I'd call the real-world risk low. Still, since tapentadol is an opioid, it's always smart to run any new supplement past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

Tapentadol also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP2C9; however, a small clinical study found no effect.
In vitro evidence suggests that red clover might inhibit CYP2C9. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of tolbutamide, a CYP2C9 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version for tapentadol (Nucynta): the worry on paper is that red clover's isoflavones might slow down a liver enzyme called CYP2C9, which could let certain drugs build up. But this is really a non-issue for tapentadol. Your body clears tapentadol mostly by attaching it to a sugar molecule (glucuronidation), not through CYP2C9, so this particular pathway isn't a big player here.

On top of that, the evidence is very weak. It comes from lab dish studies, and a small human study actually found red clover didn't change how a CYP2C9 drug behaved. I wouldn't expect extra drowsiness, dizziness, or breathing problems from this combo. Still, since tapentadol is a strong opioid, it's always worth a quick check with your pharmacist or doctor before adding any supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. 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

Red Clover Also Interacts With Other Medications

Red Clover has 44 moderate, 822 minor known drug interactions in our database — the Tapentadol one above is among them. If you take anything else, check it against the full list below.

Moderate 44 Minor 822 No known interaction 1,964 (incl. Tapentadol)
Taking anything else?

Check Another of Your Medications Against Red Clover

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

From our Q&A

Questions About Red Clover or Tapentadol

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Red Clover or Tapentadol, 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 Tapentadol

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tapentadol page lists 113 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Lithium (major), 5-htp (moderate), Acetyl-l-carnitine (moderate) and Adrafinil (moderate).

By severity: 2 major · 84 moderate · 27 minor.

From our pharmacist’s overview on the Tapentadol page

“Tapentadol (Nucynta, Nucynta ER) is an opioid painkiller that also boosts serotonin signaling on its own, and that is exactly where its supplement list bites hardest. The two major-rated entries among the 113 on file deserve a hard look first: lithium, which alongside a serotonergic drug like tapentadol can raise the risk of serotonin…”

Reviewed by 2 · Jul 18, 2026

Open the Tapentadol interaction page

One more smart check

Taking Red Clover as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,480 real supplement products containing Red Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Red Clover. Your product may carry other ingredients that interact with Tapentadol too, on top of Red Clover — 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 Red Clover and Tapentadol 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 Red Clover
Top 25%

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

29 days ago today
Medication Tapentadol
Top half

#817 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 Red Clover

What is Red Clover?

Red Clover
  • Menopause symptoms (hot flashes)
  • High cholesterol
  • Bone health/osteoporosis
  • Skin and hair concerns
  • Women's health

Red clover is a plant rich in isoflavones (plant compounds with weak estrogen-like activity) that is most often used for menopause symptoms like hot flashes. The evidence is mixed and generally weak, with some studies showing modest benefit and others showing none. Because of its hormone-like effects, it's not for everyone—talk with your pharmacist or doctor before trying it, especially if you have a hormone-sensitive condition.

Read the full Red Clover monograph & all interactions
Medication

About Tapentadol

What Is Tapentadol Used For?

Brand names: Nucynta, Nucynta ER

Tapentadol tablets (including Nucynta and Tapentadol Hydrochloride tablets) are used for severe acute pain in adults when other treatments are not adequate. Nucynta tablets are also approved for acute pain in children aged 6 and older who weigh at least 40 kg.

Nucynta ER and tapentadol extended-release tablets are used for severe, ongoing pain that requires around-the-clock opioid treatment and cannot be managed with other options, including severe neuropathic pain (nerve pain) caused by diabetic peripheral neuropathy in adults. Extended-release formulations are not intended for as-needed use.

See full Tapentadol drug information
Keep checking

Other Drugs & Red Clover

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

0Major
44Moderate
822Minor
1,963No known interaction
44 Moderate 822 Minor 1,963 No interaction
Moderate

44 interactions

Minor

822 interactions

Showing 60 of 822 minor interactions — see all 822 on the Red Clover page.

No interaction 1,963 drugs checked — show the list

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

Showing the 60 most looked-up of 1,963 medications checked with no known interaction — see the full Red Clover list.

See the full Red Clover interactions page
See every supplement checked against Tapentadol, 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
Red Clover monograph › Uses, safety, and every drug interaction in one place Tapentadol supplement interactions › Every supplement checked against Tapentadol, ranked by severity Tapentadol drug information › The full plain-English guide to this medication 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 Red Clover and Tapentadol Together: Common Questions

Can you take Red Clover with Tapentadol?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Red Clover and Tapentadol?
Tapentadol belongs to more than one drug category, and Red Clover 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 Red Clover and Tapentadol interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Tapentadol and Red Clover?

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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.