Drug & supplement interaction

Milk Thistle + Ergotamine, Belladonna, Phenobarbital

Ergotamine, Belladonna, Phenobarbital brand names: Bellaspas, Bellamine, Eperbel-S.

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

Ergotamine, Belladonna, Phenobarbital falls into 2 drug categories that Milk Thistle can interact with; the most serious is rated moderate. Theoretically, milk thistle might inhibit CYP2B6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Milk Thistle and Ergotamine, Belladonna, Phenobarbital

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. Ergotamine, Belladonna, Phenobarbital 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 (Moderate).

Moderate

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

1 of 2

Why this applies to Ergotamine, Belladonna, Phenobarbital

Ergotamine, Belladonna, Phenobarbital falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES — the group Milk Thistle interacts with.

Theoretically, milk thistle might inhibit CYP2B6.
An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels.
Severity Moderate 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

This combination product contains phenobarbital, a barbiturate that your liver partly clears using an enzyme called CYP2B6. In test-tube studies, a milk thistle compound (silybin) appeared to slow this enzyme down. If that happened in real life, phenobarbital could build up a bit more than usual, which might mean extra drowsiness, dizziness, slowed breathing, or grogginess.

Here's the honest part: this concern comes only from lab research, not from people, so we really don't know if it matters in everyday use. Phenobarbital is a sensitive medicine where small changes can count, so I wouldn't start milk thistle on your own. Just check with your pharmacist or doctor first so they can keep an eye on you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhang W, Zhang Y, Wen C, Jiang X, Wang L. In vitro Assessment of the Effects of Silybin on CYP2B6-mediated Metabolism. Planta Med 2023. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Ergotamine, Belladonna, Phenobarbital 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

This combination product blends ergotamine (for migraines), belladonna (a drying agent), and phenobarbital (a sedative). The piece that interacts here is ergotamine, which the liver clears partly through an enzyme called CYP3A4. The theory is that milk thistle might slow that enzyme, letting ergotamine build up. With ergot drugs, even modest extra exposure matters, because too much can cause cold or tingling hands and feet, leg cramps, or in rare cases reduced blood flow to the limbs.

The honest news is that this concern rests on shaky, conflicting lab evidence. Actual human studies didn't show milk thistle meaningfully changing CYP3A4 drugs, so a real-world problem is unlikely. Still, since ergotamine has a narrow safety window, it's worth a quick word with your pharmacist or doctor before adding milk thistle.

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 253 moderate, 700 minor known drug interactions in our database — the Ergotamine, Belladonna, Phenobarbital one above is among them. If you take anything else, check it against the full list below.

Moderate 253 Minor 700 No known interaction 1,877 (incl. Ergotamine, Belladonna, Phenobarbital)
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 Ergotamine, Belladonna, Phenobarbital

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 Ergotamine, Belladonna, Phenobarbital, 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 Ergotamine, Belladonna, Phenobarbital

This page covers Milk Thistle only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ergotamine, Belladonna, Phenobarbital page lists 250 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 11 major · 200 moderate · 39 minor.

From our pharmacist’s overview on the Ergotamine, Belladonna, Phenobarbital page

“Sedation stacking is the risk I would put first with ergotamine, belladonna, and phenobarbital (Bellamine, Bellaspas). Phenobarbital is a barbiturate, sedating on its own, and 78 of the ingredients on this page deepen that drowsiness, alcohol most seriously of all.”

Reviewed by 2 · Jul 18, 2026

Open the Ergotamine, Belladonna, Phenobarbital 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 Ergotamine, Belladonna, Phenobarbital 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 Ergotamine, Belladonna, Phenobarbital 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%

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

29 days ago today
Medication Ergotamine, Belladonna, Phenobarbital
Top 10%

#198 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
253Moderate
700Minor
1,876No known interaction
253 Moderate 700 Minor 1,876 No interaction
Moderate

253 interactions

Showing 60 of 253 moderate interactions — see all 253 on the Milk Thistle page.

Minor

700 interactions

Showing 60 of 700 minor interactions — see all 700 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 Ergotamine, Belladonna, Phenobarbital, 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 Ergotamine, Belladonna, Phenobarbital supplement interactions › Every supplement checked against Ergotamine, Belladonna, Phenobarbital, 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 Ergotamine, Belladonna, Phenobarbital Together: Common Questions

Can you take Milk Thistle with Ergotamine, Belladonna, Phenobarbital?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. 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 Ergotamine, Belladonna, Phenobarbital?
Ergotamine, Belladonna, Phenobarbital 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 Ergotamine, Belladonna, Phenobarbital interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Ergotamine, Belladonna, Phenobarbital and Milk Thistle?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.