Drug & supplement interaction

Milk Thistle + Esomeprazole, Naproxen

Esomeprazole, Naproxen brand name: Vimovo.

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

Esomeprazole, Naproxen falls into 2 drug categories that Milk Thistle can interact with; the most serious is rated minor. It is unclear if milk thistle inhibits CYP2C9; research is conflicting.

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

Milk Thistle and Esomeprazole, Naproxen

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

Why Are There 2 Interactions?

Milk Thistle interacts with whole categories of medication. Esomeprazole, Naproxen falls into 2 of those categories, so it can interact with Milk Thistle 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 2C9 (CYP2C9) SUBSTRATES

1 of 2

Why this applies to Esomeprazole, Naproxen

Esomeprazole, Naproxen falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Milk Thistle interacts with.

It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
In vitro research suggests that milk thistle might inhibit CYP2C9. Additionally, 3 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP2C9 substrates, including imatinib and capecitabine. However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide. Differences in results could be due to differences in dosages or formulations utilized.
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

Vimovo combines naproxen (an anti-inflammatory pain reliever) with esomeprazole (a stomach-acid blocker). The naproxen part is partly cleared by a liver enzyme called CYP2C9, and there's a theory that milk thistle's silymarin might slow that enzyme down. If it did, naproxen could linger a bit longer and possibly nudge up its usual side effects, things like stomach upset, heartburn, fluid retention, or kidney strain.

Here's the honest picture though: the evidence is weak and conflicting. Some lab tests hint milk thistle blocks CYP2C9, but better human studies suggest it doesn't really change drug levels. Our database rates this as minor and unlikely. For most people this combo is fine, but if you take milk thistle daily, it's worth a quick mention to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, et al. Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 2000;86:250-6. PubMed
  2. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76:428-40. .
  3. Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94. PubMed
  4. Doehmer J, Weiss G, McGregor GP, Appel K. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011;25:21-7. PubMed
  5. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-6. PubMed
  6. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Esomeprazole, Naproxen also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.
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

Vimovo combines two medicines: esomeprazole (an acid reducer) and naproxen (an anti-inflammatory pain reliever). The concern on file is whether milk thistle might block a liver enzyme called CYP3A4 and let these drugs build up. Honestly, the evidence here is weak. It comes mostly from lab dishes and a handful of cancer-drug case reports, and human studies found milk thistle did not meaningfully change CYP3A4-cleared medicines.

On top of that, neither esomeprazole nor naproxen relies heavily on CYP3A4 (esomeprazole mainly uses CYP2C19, and naproxen uses CYP2C9). So a real-world problem is unlikely. If you did get higher levels, you might notice more naproxen-type effects like stomach upset or heartburn. Just let your pharmacist know you take both, and you're fine to ask.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3. DOI
  2. Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22:551-6. PubMed
  3. Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94. PubMed
  4. van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005;11:7800-6.
  5. Budzinski JW, Trudeau VL, Drouin CE, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 2007;85:966-78.
  6. Doehmer J, Weiss G, McGregor GP, Appel K. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011;25:21-7. PubMed
  7. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  8. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-6. PubMed
  9. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. 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

Milk Thistle Also Interacts With Other Medications

Milk Thistle has 254 moderate, 699 minor known drug interactions in our database — the Esomeprazole, Naproxen one above is among them. If you take anything else, check it against the full list below.

Moderate 254 Minor 699 No known interaction 1,877 (incl. Esomeprazole, Naproxen)
Taking anything else?

Check Another of Your Medications Against Milk Thistle

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

From our Q&A

Questions About Milk Thistle or Esomeprazole, Naproxen

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Milk Thistle or Esomeprazole, Naproxen, 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 Esomeprazole, Naproxen

This page covers Milk Thistle only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Esomeprazole, Naproxen page lists 348 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Grapefruit (major).

By severity: 9 major · 283 moderate · 56 minor.

From our pharmacist’s overview on the Esomeprazole, Naproxen page

“Bleeding risk is the thread running through nearly this whole page. Vimovo pairs naproxen, an anti-inflammatory that already makes stomach bleeding more likely, with esomeprazole on board to shield the gut, and most of the supplements flagged here could push that bleeding risk higher still.”

Reviewed by 2 · Jul 18, 2026

Open the Esomeprazole, Naproxen interaction page

One more smart check

Taking Milk Thistle as Part of a Dietary Supplement Product? Check It for Interactions

We hold 4,560 real supplement products containing Milk Thistle, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Milk Thistle. Your product may carry other ingredients that interact with Esomeprazole, Naproxen too, on top of Milk Thistle — 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 Milk Thistle and Esomeprazole, Naproxen 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 Milk Thistle
Top 5%

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

29 days ago today
Medication Esomeprazole, Naproxen
Steady interest

#2,105 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 Milk Thistle

What is Milk Thistle?

Milk Thistle
  • Liver health and protection
  • Hepatitis
  • Cirrhosis
  • Gallbladder problems
  • High cholesterol
  • Type 2 diabetes support

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin. While it is generally well tolerated, the scientific evidence that it meaningfully improves liver disease or other conditions is mixed and far from conclusive. Talk with your pharmacist or doctor before using it, especially if you have a liver condition or take other medicines.

Read the full Milk Thistle monograph & all interactions
Keep checking

Other Drugs & Milk Thistle

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

0Major
254Moderate
699Minor
1,876No known interaction
254 Moderate 699 Minor 1,876 No interaction
Moderate

254 interactions

Showing 60 of 254 moderate interactions — see all 254 on the Milk Thistle page.

Minor

699 interactions

Showing 60 of 699 minor interactions — see all 699 on the Milk Thistle page.

No interaction 1,876 drugs checked — show the list

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

Showing the 60 most looked-up of 1,876 medications checked with no known interaction — see the full Milk Thistle list.

See the full Milk Thistle interactions page
See every supplement checked against Esomeprazole, Naproxen, 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
Milk Thistle monograph › Uses, safety, and every drug interaction in one place Esomeprazole, Naproxen supplement interactions › Every supplement checked against Esomeprazole, Naproxen, 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 Milk Thistle and Esomeprazole, Naproxen Together: Common Questions

Can you take Milk Thistle with Esomeprazole, Naproxen?
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 Milk Thistle and Esomeprazole, Naproxen?
Esomeprazole, Naproxen belongs to more than one drug category, and Milk Thistle 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 Milk Thistle and Esomeprazole, Naproxen 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 Esomeprazole, Naproxen and Milk Thistle?

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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.