Drug & supplement interaction

St. John's Wort + Ledipasvir, Sofosbuvir

Ledipasvir, Sofosbuvir brand name: Harvoni.

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

St. John's Wort has a major interaction with Ledipasvir, Sofosbuvir. St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.

Read the full interaction report
SeverityMajor
LikelihoodProbable
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

St. John's Wort and Ledipasvir, Sofosbuvir

Here is the interaction we found between these two, with the evidence behind it.

Major

P-GLYCOPROTEIN SUBSTRATES

Why this applies to Ledipasvir, Sofosbuvir

Ledipasvir, Sofosbuvir falls under P-GLYCOPROTEIN SUBSTRATES — the group St. John's Wort interacts with.

St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.
St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action.
Severity Major Likelihood Probable Evidence B

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the concern with pairing Harvoni (ledipasvir/sofosbuvir) with St. John's wort. Both of these antiviral ingredients are moved around by a transporter called P-glycoprotein. St. John's wort speeds that transporter up, which can pump more of the drug back out before your body absorbs it. The result is lower blood levels of your hepatitis C medicine.

That really matters here. With Harvoni, the whole point is to keep enough drug in your system to fully clear the virus. If levels drop, the treatment may not work, and you could end up with a failed cure or even a virus that's harder to treat later. This combination is generally considered something to avoid. Please don't stop either one on your own, but do talk with your doctor or pharmacist before starting St. John's wort.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
  2. Durr D, Stieger B, Kullak-Ublick GA, et al. St. John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000;68:598-604. PubMed
  3. Hennessy M, Kelleher D, Spiers JP, et al. St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002;53:75-82.
  4. Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev 2002;34:47-54. 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

St. John's Wort Also Interacts With Other Medications

St. John's Wort has 754 major, 388 moderate known drug interactions in our database — the Ledipasvir, Sofosbuvir one above is one of them. If you take anything else, check it against the full list below.

Major 754 Moderate 388 No known interaction 1,688 (incl. Ledipasvir, Sofosbuvir)
Taking anything else?

Check Another of Your Medications Against St. John's Wort

Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.

From our Q&A

Questions About St. John's Wort 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 St. John's Wort 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 St. John's Wort 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), Bitter Melon (moderate), Black Pepper (moderate), Bulbine Natalensis (moderate) and Cannabis (moderate).

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

Open the Ledipasvir, Sofosbuvir interaction page

One more smart check

Taking St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Ledipasvir, Sofosbuvir too, on top of St. John's Wort — 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 St. John's Wort 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 St. John's Wort
Top 25%

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

29 days ago today
Medication Ledipasvir, Sofosbuvir
Top 25%

#551 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 St. John's Wort

What is St. John's Wort?

St. John's Wort
  • Mild to moderate depression
  • Anxiety and stress
  • Sleep problems
  • Menopausal symptoms
  • Wound healing (topical)

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.

Read the full St. John's Wort 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 & St. John's Wort

Browse every other medication we’ve checked against St. John's Wort — both the ones with a known interaction and the ones without. Select any drug for the full detail.

754Major
388Moderate
0Minor
1,687No known interaction
754 Major 388 Moderate 1,687 No interaction
Major

754 interactions

Showing 60 of 754 major interactions — see all 754 on the St. John's Wort page.

Moderate

388 interactions

Showing 60 of 388 moderate interactions — see all 388 on the St. John's Wort page.

No interaction 1,687 drugs checked — show the list

We also checked St. John's Wort against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,687 medications checked with no known interaction — see the full St. John's Wort list.

See the full St. John's Wort 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
St. John's Wort 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 St. John's Wort and Ledipasvir, Sofosbuvir Together: Common Questions

Can you take St. John's Wort with Ledipasvir, Sofosbuvir?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the St. John's Wort and Ledipasvir, Sofosbuvir interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Ledipasvir, Sofosbuvir and St. John's Wort?

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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.