Drug & supplement interaction

Red Clover + Cyclobenzaprine

Cyclobenzaprine brand names: Cyclobenzaprine, Flexeril, Cycloprine.

Minor Interaction
The bottom line Minor

Cyclobenzaprine falls into 2 drug categories that Red Clover can interact with; the most serious is rated minor. Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.

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

Red Clover and Cyclobenzaprine

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. Cyclobenzaprine 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 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Cyclobenzaprine

Cyclobenzaprine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Red Clover interacts with.

Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
In vitro evidence shows that red clover inhibits CYP1A2. 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 caffeine, a CYP1A2 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 gist for these two together. Your body clears cyclobenzaprine partly through a liver enzyme called CYP1A2. In a test tube, red clover's isoflavones can slow that enzyme down a bit. If that slowing happened in real life, cyclobenzaprine could hang around a little longer and you might feel more of its usual effects, like drowsiness, dizziness, dry mouth, or a groggy, foggy feeling.

The reassuring part: this concern comes only from lab studies. When researchers actually tested red clover in people, it did not change how the body handled a CYP1A2 marker (caffeine). So a real-world problem is unlikely and would be minor at most. Still, since both can make you sleepy, it's worth a quick check with your pharmacist or doctor.

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
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Cyclobenzaprine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.
In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes. 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 alprazolam, a CYP3A4 probe substrate.
Severity Minor Likelihood Unlikely Evidence B

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 gist with red clover and cyclobenzaprine. Cyclobenzaprine is broken down in part by a liver enzyme called CYP3A4. In a test tube, red clover's plant estrogens look like they might slow that enzyme down a little, which could in theory let cyclobenzaprine build up and make its usual effects (drowsiness, dry mouth, dizziness, blurry vision) more noticeable.

The good news is that this is mostly a paper concern. When researchers actually tested red clover capsules in people, it didn't meaningfully change how the body handled a similar CYP3A4 medication. So a real-world problem here is considered unlikely and minor. Still, if you notice extra grogginess, mention it to your pharmacist or doctor before changing anything.

References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. 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
  3. 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 Cyclobenzaprine 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 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 Cyclobenzaprine

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 Cyclobenzaprine, 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 Cyclobenzaprine

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclobenzaprine page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lithium (major), Procaine (major) and St. John's Wort (major).

By severity: 5 major · 146 moderate · 46 minor.

Open the Cyclobenzaprine 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 Cyclobenzaprine 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 Cyclobenzaprine 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%

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

29 days ago today
Medication Cyclobenzaprine
Top 25%

#326 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 Cyclobenzaprine

What Is Cyclobenzaprine Used For?

Brand names: Cyclobenzaprine, Flexeril, Cycloprine

Cyclobenzaprine tablets and extended-release capsules are used alongside rest and physical therapy to relieve muscle spasm caused by acute, painful musculoskeletal conditions — easing pain, tenderness, and limited movement. This use is intended for short-term treatment only (up to 2–3 weeks).

Tonmya, the sublingual (under-the-tongue) form of cyclobenzaprine, is separately indicated for the treatment of fibromyalgia in adults. It is not the same as the oral tablet or capsule formulations.

See full Cyclobenzaprine 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
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
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 Red Clover and Cyclobenzaprine Together: Common Questions

Can you take Red Clover with Cyclobenzaprine?
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 Cyclobenzaprine?
Cyclobenzaprine 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 Cyclobenzaprine 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 Cyclobenzaprine 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.