Drug & supplement interaction

Milk Thistle + Dolutegravir, Rilpivirine

Dolutegravir, Rilpivirine brand name: Juluca.

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

Dolutegravir, Rilpivirine falls into 3 drug categories that Milk Thistle can interact with; the most serious is rated moderate. Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Milk Thistle and Dolutegravir, Rilpivirine

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. Dolutegravir, Rilpivirine 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 (Moderate).

Moderate

GLUCURONIDATED DRUGS

1 of 3

Why this applies to Dolutegravir, Rilpivirine

Dolutegravir, Rilpivirine falls under GLUCURONIDATED DRUGS — the group Milk Thistle interacts with.

Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.
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

Here's the situation with Juluca, which is a two-in-one HIV pill combining dolutegravir and rilpivirine. Dolutegravir is cleared from your body partly through a process called glucuronidation (handled by enzymes called UGTs). In lab and animal studies, milk thistle's silymarin compounds appear to slow those UGT enzymes down. In theory, that could let dolutegravir levels creep up a bit, which might mean more side effects like headache, trouble sleeping, or nausea.

I want to be honest: this is theoretical and based only on test-tube and animal data, not real people, so it may not amount to much in practice. Still, since keeping your HIV treatment steady matters, please run milk thistle by your pharmacist or doctor before adding it. Don't change your Juluca on your own.

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. Kim DH, Jin YH, Park JB, Kobashi K. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull 1994;17:443-5. 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
Minor

P-GLYCOPROTEIN SUBSTRATES

2 of 3

Dolutegravir, Rilpivirine also falls under P-GLYCOPROTEIN SUBSTRATES.

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

Juluca combines two HIV medicines, dolutegravir and rilpivirine, and both can be moved around the body by a transporter pump called P-glycoprotein. On paper, milk thistle's main compound (silymarin) can slow that pump a little, which could let slightly more drug be absorbed. In theory that might bump up side effects like headache, trouble sleeping, mild stomach upset, or unusual dreams.

Here's the reassuring part: this is mostly a lab-based, theoretical concern. In a real human study, milk thistle didn't meaningfully change levels of a similar P-glycoprotein drug. So a real-world problem is unlikely. Still, since keeping HIV treatment steady matters, just let your pharmacist or doctor know before you add milk thistle.

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

3 of 3

Dolutegravir, Rilpivirine 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

If you take Juluca (dolutegravir plus rilpivirine) and you're curious about milk thistle, here's the honest picture. The rilpivirine part is processed by a liver enzyme called CYP3A4, and in theory milk thistle could slow that enzyme down. If that happened, rilpivirine levels might creep up, which could mean more side effects like headache, trouble sleeping, odd dreams, or mood changes.

The good news is that the actual evidence for this is weak. Human studies show milk thistle usually doesn't meaningfully change CYP3A4 drugs, and our database rates this as minor and unlikely. Still, keeping HIV treatment steady really matters, so check with your pharmacist or doctor before adding milk thistle rather than starting or stopping anything on your own.

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 Dolutegravir, Rilpivirine 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. Dolutegravir, Rilpivirine)
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 Dolutegravir, Rilpivirine

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 Dolutegravir, Rilpivirine, 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 Dolutegravir, Rilpivirine

This page covers Milk Thistle only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Dolutegravir, Rilpivirine page lists 159 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Calcium (major) and Cesium (major).

By severity: 9 major · 115 moderate · 35 minor.

From our pharmacist’s overview on the Dolutegravir, Rilpivirine page

“Juluca combines dolutegravir and rilpivirine into a single daily HIV pill, and staying suppressed depends on that pill working at full strength every day, which is why this list calls for real vigilance. Most of the 159 interacting supplements and herbs change how the body handles the medication, some raising its levels and others lowe…”

Reviewed by 2 · Jul 18, 2026

Open the Dolutegravir, Rilpivirine 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 Dolutegravir, Rilpivirine 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 Dolutegravir, Rilpivirine 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%

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

29 days ago today
Medication Dolutegravir, Rilpivirine
Steady interest

#1,922 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 Dolutegravir, Rilpivirine, 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 Dolutegravir, Rilpivirine supplement interactions › Every supplement checked against Dolutegravir, Rilpivirine, 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 Dolutegravir, Rilpivirine Together: Common Questions

Can you take Milk Thistle with Dolutegravir, Rilpivirine?
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 3 interactions listed for Milk Thistle and Dolutegravir, Rilpivirine?
Dolutegravir, Rilpivirine 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 Dolutegravir, Rilpivirine 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

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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.