Drug & supplement interaction

Red Clover + Aspirin, Caffeine, Dihydrocodeine Bitartrate

Aspirin, Caffeine, Dihydrocodeine Bitartrate brand name: Synalgos DC.

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

Aspirin, Caffeine, Dihydrocodeine Bitartrate falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Red Clover and Aspirin, Caffeine, Dihydrocodeine Bitartrate

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Red Clover interacts with whole categories of medication. Aspirin, Caffeine, Dihydrocodeine Bitartrate falls into 4 of those categories, so it can interact with Red Clover in 4 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 4

Why this applies to Aspirin, Caffeine, Dihydrocodeine Bitartrate

Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 piece that actually matters for Synalgos DC: the caffeine in it is cleared by a liver enzyme called CYP1A2. In lab (test tube) studies, red clover slowed that enzyme down a bit. On paper, that could let caffeine build up and add to its usual effects, things like jitteriness, a faster heartbeat, or trouble sleeping.

But here's the reassuring part: when researchers actually tested this in people taking standardized red clover for two weeks, caffeine levels didn't budge. So this is a theoretical, very weak concern, not something most people will ever notice. The aspirin and dihydrocodeine pieces aren't really involved here. Still, if you take this regularly, it never hurts to mention the red clover to your pharmacist.

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
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 for Synalgos DC (a combo of aspirin, caffeine, and dihydrocodeine). The concern on file is that red clover's isoflavones might block the CYP3A4 enzyme, which helps process the dihydrocodeine portion. In a test tube, red clover slowed this enzyme down, but when researchers actually gave people standardized red clover for two weeks, it didn't change how a CYP3A4-handled drug behaved. So this is mostly theoretical.

Worth knowing: dihydrocodeine is a prodrug partly activated by CYP2D6, not 3A4, so the picture is a bit muddy. In plain terms, I wouldn't expect a meaningful change in your pain relief or in side effects like drowsiness, constipation, or stomach upset. Still, since opioids and aspirin carry their own risks, run the combo by your pharmacist first.

Contact Dr. Brian directly if you have additional questions on this interaction
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
Minor

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Although some laboratory research suggests that red clover may have anticoagulant and antiplatelet activity, clinical research has not shown this effect.
In vitro research suggests that genistein in red clover has antiplatelet effects, and historically, red clover was thought to have anticoagulant effects due to its coumarin content. However, some experts state that this is unlikely as most natural coumarins have not been shown to have anticoagulant effects, and their content in red clover is low. Additionally, some clinical research in postmenopausal patients found no effect on coagulation or prothrombin time with the use of red clover flowering tops 378 mg daily for 12 months or red clover isoflavone (Rimostil) 50 mg daily for 2 years.
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 short version on combining red clover with Synalgos DC (which contains aspirin, caffeine, and dihydrocodeine): the concern people raise is that red clover might add to aspirin's blood-thinning effect. In a test tube, one of red clover's isoflavones (genistein) showed mild antiplatelet activity, and the plant has tiny amounts of coumarins. On paper that could stack with aspirin and, in theory, mean a little more bruising or slower clotting.

But the actual human studies don't back this up. Trials in postmenopausal women taking red clover for up to two years found no real change in clotting or bleeding tests. So this is a minor, unlikely interaction. Still, if you're on aspirin and notice easy bruising, nosebleeds, or any unusual bleeding, mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Geller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 2009;16:1156-66. PubMed
  2. Guerrero JA, Lozano ML, Castillo J, et al. Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost 2005;3(2):369-376. PubMed
  3. Kondo K, Suzuki Y, Ikeda Y, Umemura K. Genistein, an isoflavone included in soy, inhibits thrombotic vessel occlusion in the mouse femoral artery and in vitro platelet aggregation. Eur J Pharmacol 2002;455(1):53-57. PubMed
  4. Polini N, Rauschemberger MB, Mendiberri J, et al. Effect of genistein and raloxifene on vascular dependent platelet aggregation. Mol Cell Endocrinol 2007;267(1-2):55-62. PubMed
  5. Clifton-Bligh PB, et al. Red cover isoflavones enriched with formononetin lower serum LDL cholesterol- a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. 2015;69(1):134-142.
Minor

CAFFEINE

4 of 4

Aspirin, Caffeine, Dihydrocodeine Bitartrate also falls under CAFFEINE.

Theoretically, soy might reduce the clearance of caffeine; however, a small clinical study found no effect.
Red clover contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females. However, this effect does not seem to occur with the lower amounts of genistein found in red clover. 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.
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 Synalgos DC, which is a combination of aspirin, caffeine, and dihydrocodeine. The only piece that touches red clover is the caffeine. In theory, a concentrated isoflavone called genistein can slow how your body clears caffeine, so caffeine could linger a bit longer and leave you feeling jittery, restless, or having trouble sleeping. The aspirin and dihydrocodeine parts aren't involved here.

The reassuring news: this only showed up at very high genistein doses (about 1 gram daily). At the normal isoflavone levels found in red clover supplements, studies found no real effect on caffeine. So this is mostly theoretical and unlikely to cause a problem. Still, it's always smart to run any new supplement by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chen, Y., Xiao, C. Q., He, Y. J., Chen, B. L., Wang, G., Zhou, G., Zhang, W., Tan, Z. R., Cao, S., Wang, L. P., and Zhou, H. H. Genistein alters caffeine exposure in healthy female volunteers. Eur.J Clin.Pharmacol. 2011;67(4):347-353. 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate 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. Aspirin, Caffeine, Dihydrocodeine Bitartrate)
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.

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Dihydrocodeine Bitartrate

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Dihydrocodeine Bitartrate page lists 398 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 Danshen (major).

By severity: 17 major · 334 moderate · 47 minor.

Open the Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate 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%

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

29 days ago today
Medication Aspirin, Caffeine, Dihydrocodeine Bitartrate
Steady interest

#1,533 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
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 Aspirin, Caffeine, Dihydrocodeine Bitartrate, 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate supplement interactions › Every supplement checked against Aspirin, Caffeine, Dihydrocodeine Bitartrate, 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 Red Clover and Aspirin, Caffeine, Dihydrocodeine Bitartrate Together: Common Questions

Can you take Red Clover with Aspirin, Caffeine, Dihydrocodeine Bitartrate?
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 4 interactions listed for Red Clover and Aspirin, Caffeine, Dihydrocodeine Bitartrate?
Aspirin, Caffeine, Dihydrocodeine Bitartrate 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 Aspirin, Caffeine, Dihydrocodeine Bitartrate 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

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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.