Drug & supplement interaction

Milk Thistle + Ledipasvir, Sofosbuvir

Ledipasvir, Sofosbuvir brand name: Harvoni.

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

Ledipasvir, Sofosbuvir falls into 3 drug categories that Milk Thistle can interact with; the most serious is rated moderate. Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.

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

Milk Thistle and Ledipasvir, Sofosbuvir

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. Ledipasvir, Sofosbuvir 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

SOFOSBUVIR (Solvaldi)

1 of 3
Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite.
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 is the gist for Harvoni (ledipasvir and sofosbuvir). Sofosbuvir is actually a prodrug, meaning your body has to switch it on before it can fight the hepatitis C virus. There is a theory that milk thistle could get in the way of that activation and lower how much of the working drug reaches your liver. If that happened, the worry is a weaker punch against the virus, which matters because a full course of Harvoni is meant to clear the infection completely.

I want to be honest about the strength of this, though. The concern comes only from rat studies, not from people, so it is more of a caution flag than a proven problem. Since clearing hepatitis C is the whole goal, I would not add milk thistle without first checking with your pharmacist or the doctor managing your treatment.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Aboras SI, Korany MA, El-Yazbi AF, Ragab MAA, Abdine HH. In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS. Biomed Chromatogr 2022;36(9):e5427. PubMed
Moderate

LEDIPASVIR

2 of 3
Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination.
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 is the gist for Harvoni (ledipasvir/sofosbuvir). The concern is with the ledipasvir part. In rat studies, milk thistle slowed how fast the body cleared ledipasvir, which let more of it build up in the bloodstream. In theory, higher levels could mean a bit more chance of the usual side effects people see with Harvoni, like tiredness, headache, or nausea.

I want to be honest about the strength of this, though. It comes from lab and animal research only, not from people, so it is a theoretical caution rather than something we know happens in real life. Since you are taking Harvoni to clear hepatitis C, I would not add or stop milk thistle on your own. Just run it by your pharmacist or doctor first so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Aboras SI, Korany MA, El-Yazbi AF, Ragab MAA, Abdine HH. In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS. Biomed Chromatogr 2022;36(9):e5427. PubMed
Minor

P-GLYCOPROTEIN SUBSTRATES

3 of 3

Why this applies to Ledipasvir, Sofosbuvir

Ledipasvir, Sofosbuvir 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 Harvoni (ledipasvir and sofosbuvir). Both pieces of this medicine are moved around the body by a transporter called P-glycoprotein. In the test tube, milk thistle can slow that transporter down, and in theory that could let a little more of the drug get absorbed. The concern would be slightly stronger side effects like tiredness, headache, or nausea.

In real life, though, this looks very unlikely to cause trouble. A human study found milk thistle didn't change levels of digoxin, another drug handled the same way. Harvoni is not a prodrug, so it doesn't get flipped around. Still, since milk thistle and Harvoni are both used for liver health, it's worth a quick check with your pharmacist or doctor before combining them.

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

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 Ledipasvir, Sofosbuvir 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. Ledipasvir, Sofosbuvir)
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 Ledipasvir, Sofosbuvir

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 Ledipasvir, Sofosbuvir, 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 Ledipasvir, Sofosbuvir

This page covers Milk Thistle only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ledipasvir, Sofosbuvir page lists 55 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), St. John's Wort (major), Bitter Melon (moderate), Black Pepper (moderate) and Bulbine Natalensis (moderate).

By severity: 2 major · 37 moderate · 16 minor.

Open the Ledipasvir, Sofosbuvir 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 Ledipasvir, Sofosbuvir 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 Ledipasvir, Sofosbuvir 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 Ledipasvir, Sofosbuvir
Top 25%

#574 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 Ledipasvir and Sofosbuvir

What Is Ledipasvir and Sofosbuvir Used For?

Brand name: Harvoni

Ledipasvir and sofosbuvir treats chronic hepatitis C virus (HCV) infection in adults and pediatric patients 3 years of age and older. It is approved for HCV genotypes 1, 4, 5, and 6 in patients without cirrhosis or with compensated cirrhosis (mild-to-moderate liver scarring that the liver is still managing), and for genotype 1 with decompensated cirrhosis (advanced liver disease) when used together with ribavirin.

It is also approved for liver transplant recipients with HCV genotype 1 or 4 infection who do not have cirrhosis or have compensated cirrhosis, in combination with ribavirin. Both Harvoni and the generic ledipasvir and sofosbuvir tablets share these indications.

See full Ledipasvir and Sofosbuvir 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
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 Ledipasvir, Sofosbuvir, 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 Ledipasvir, Sofosbuvir supplement interactions › Every supplement checked against Ledipasvir, Sofosbuvir, ranked by severity Ledipasvir and Sofosbuvir 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 Ledipasvir, Sofosbuvir Together: Common Questions

Can you take Milk Thistle with Ledipasvir, Sofosbuvir?
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 Ledipasvir, Sofosbuvir?
Ledipasvir, Sofosbuvir 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 Ledipasvir, Sofosbuvir 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.