Drug & supplement interaction

Milk Thistle + Etoposide

Etoposide brand names: VePesid, VP16, Etopophos.

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

Etoposide falls into 3 drug categories that Milk Thistle can interact with; the most serious is rated minor. Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Milk Thistle and Etoposide

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Milk Thistle interacts with whole categories of medication. Etoposide falls into 3 of those categories, so it can interact with Milk Thistle in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

P-GLYCOPROTEIN SUBSTRATES

1 of 3

Why this applies to Etoposide

Etoposide falls under P-GLYCOPROTEIN SUBSTRATES — the group Milk Thistle interacts with.

Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
In vitro research shows that milk thistle can inhibit P-glycoprotein activity and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate. However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein 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 milk thistle and etoposide. Etoposide is partly moved around your body by a transporter called P-glycoprotein, which acts like a gatekeeper. In lab studies, milk thistle can block that gatekeeper a little, and in theory that might let slightly more etoposide get absorbed. More drug in your system could, in principle, mean stronger side effects like low blood counts (raising infection risk), nausea, mouth sores, or fatigue.

The reassuring part: this is mostly theoretical. Human studies haven't shown a meaningful change, so it's rated minor and unlikely. Still, etoposide is serious chemotherapy, so please don't add milk thistle without first checking with your oncologist or pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Gurley, B. J., Barone, G. W., Williams, D. K., Carrier, J., Breen, P., Yates, C. R., Song, P. F., Hubbard, M. A., Tong, Y., and Cheboyina, S. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin phar
  2. Derosa G, Romano D, D'Angelo A, Maffioli P. Berberis aristata/Silybum marianum fixed combination (Berberol(®)) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial. Phyto PubMed
  3. 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 3

Etoposide 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

Here's the short version on pairing milk thistle with etoposide. Your body uses a liver enzyme called CYP3A4 to help clear etoposide, and the question is whether milk thistle slows that enzyme down. The honest answer is that the research is mixed. In careful human studies, milk thistle didn't meaningfully change the levels of similar CYP3A4 drugs, so for most people this is a minor and unlikely concern.

That said, etoposide is a chemotherapy drug, and a handful of case reports hinted at extra toxicity (think more bone marrow suppression, low blood counts, nausea, or fatigue) when milk thistle was mixed with cancer medicines like this. Because the stakes are high with chemo, please don't add or stop milk thistle on your own. Run it by your oncologist or pharmacist first so they can keep you safe.

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
Minor

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

3 of 3

Etoposide also falls under ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP).

Milk thistle may inhibit one form of OATP, OATP-B1, which could reduce the bioavailability and clinical effects of OATP-B1 substrates.
In vitro research shows that milk thistle inhibits OATP-B1. Two 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 OATP substrates, including sorafenib and methotrexate. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.
Severity Minor 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 gist with milk thistle and etoposide. Your body uses transporters called OATPs to help shuttle certain drugs from your gut into your bloodstream. Lab studies suggest milk thistle (specifically its silymarin compounds) can block one of these, called OATP-B1. In theory, that could mean less etoposide gets absorbed, which might make it work less well against the cancer.

I want to be straight with you though: this is based on test-tube research and a couple of scattered case reports, not solid human studies, so it's far from proven. The interaction is rated minor. Still, because etoposide is chemotherapy where dosing really matters, please don't add milk thistle without first checking with your oncologist or pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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 Etoposide 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. Etoposide)
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 Etoposide

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 Etoposide, 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 Etoposide

This page covers Milk Thistle only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Etoposide page lists 152 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 5 major · 107 moderate · 40 minor.

From our pharmacist’s overview on the Etoposide page

“Chemotherapy is unforgiving of level swings, and swings are exactly what most of this list can cause for etoposide (VePesid, Etopophos). Of the 152 supplements and herbs on file, 121 can change how your liver clears etoposide through the CYP3A4 enzyme, meaning too little drug and an undertreated cancer, or too much and harsher toxicity.”

Reviewed by 2 · Jul 18, 2026

Open the Etoposide 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 Etoposide 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 Etoposide 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 Etoposide
Steady interest

#2,032 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
Medication

About Etoposide

What Is Etoposide Used For?

Brand names: VePesid, VP16, Etopophos

Etoposide injection (available as Avopef, Etopophos, Toposar, and Etoposide) is used to treat refractory testicular tumors — cancers that have already been treated with surgery, radiation, and other chemotherapy — always in combination with other cancer drugs. It is also used for small cell lung cancer (SCLC) as a first-line treatment, given together with other chemotherapy and, in the case of Avopef, with immunotherapy as well.

Etoposide capsules (VePesid and Etoposide capsules) are approved for small cell lung cancer as first-line treatment in combination with other chemotherapy agents. Capsule forms are not approved for testicular cancer, as the label notes that adequate data on their use in that setting are not available.

See full Etoposide drug information
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 Etoposide, 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 Etoposide supplement interactions › Every supplement checked against Etoposide, ranked by severity Etoposide 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 Milk Thistle and Etoposide Together: Common Questions

Can you take Milk Thistle with Etoposide?
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 3 interactions listed for Milk Thistle and Etoposide?
Etoposide 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 Etoposide 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 Etoposide 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.