Drug & supplement interaction

Comfrey + Aprocitentan

Aprocitentan brand name: Tryvio.

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

Aprocitentan falls into 2 drug categories that Comfrey can interact with; the most serious is rated moderate. Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Comfrey and Aprocitentan

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Comfrey interacts with whole categories of medication. Aprocitentan falls into 2 of those categories, so it can interact with Comfrey in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Aprocitentan

Aprocitentan falls under HEPATOTOXIC DRUGS — the group Comfrey interacts with.

Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.
Due to its pyrrolizidine alkaloid constituents, comfrey can cause hepatotoxic effects, including ascites, cirrhosis, hepatic fibrosis, hepatomegaly, and sinusoidal obstruction syndrome.
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 concern with pairing these two. Comfrey contains natural compounds called pyrrolizidine alkaloids that can be quite hard on the liver, especially when it's taken by mouth. Aprocitentan (Tryvio) is a blood pressure medicine that carries its own risk of liver strain, which is why your doctor may check liver bloodwork while you're on it.

Putting a liver-taxing herb together with a drug that can already bother the liver may add up and raise your chance of liver trouble. This is a theoretical caution based on how each one works, not proven cases, so try not to panic. Still, I'd skip oral comfrey entirely, be cautious even with skin products, and check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Food and Drug Administration. FDA Advises Dietary Supplement Manufacturers to Remove Comfrey Products From the Market. July 6, 2001. Available at: http://www.cfsan.fda.gov/~dms/dspltr06.html.
  2. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

2 of 2

Aprocitentan also falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS.

Theoretically, CYP3A4 inducers might increase the risk of adverse effects from the pyrrolizidine alkaloid constituents in comfrey.
CYP3A4 enzymes convert pyrrolizidine alkaloids, constituents of comfrey, to toxic metabolites. Some case reports show that enzyme inducers, such as phenobarbital, seem to enhance the toxicity of comfrey.
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 thing to know about pairing comfrey with Tryvio (aprocitentan). Aprocitentan can act as a mild CYP3A4 inducer, meaning it can nudge that liver enzyme to work a little faster. Comfrey contains pyrrolizidine alkaloids, and CYP3A4 is exactly the enzyme that turns those compounds into toxic byproducts that can harm the liver. So in theory, speeding up that enzyme could ramp up comfrey's liver toxicity.

I'll be honest, this is a theoretical concern based on how the two work, not something proven with this specific drug. But comfrey is genuinely risky for the liver on its own, which is why it should never be swallowed and only used briefly on intact skin. Please run this by your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutr 2000;3:501-8. PubMed
  2. Chojkier M. Hepatic sinusoidal-obstruction syndrome: toxicity of pyrrolizidine alkaloids. J Hepatol 2003;39:437-46. PubMed
  3. Wang YP, Yan J, Fu PP, Chou MW. Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid. Toxicol Lett 2005;155:411-20. 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

Comfrey Also Interacts With Other Medications

Comfrey has 437 moderate known drug interactions in our database — the Aprocitentan one above is among them. If you take anything else, check it against the full list below.

Moderate 437 No known interaction 2,393 (incl. Aprocitentan)
Taking anything else?

Check Another of Your Medications Against Comfrey

Covers the 2,830 medications we’ve checked against Comfrey. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Aprocitentan

This page covers Comfrey only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aprocitentan page lists 189 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Beer (major) and Siberian Cocklebur (major).

By severity: 7 major · 161 moderate · 21 minor.

From our pharmacist’s overview on the Aprocitentan page

“Aprocitentan (Tryvio) is prescribed when blood pressure stays high despite other medicines, so anything that pushes your pressure around cuts straight to why you take it. Most of the 189 ingredients here do exactly that: some add to the drop and can leave you dizzy or faint, while others, tyramine among them, push pressure back up and…”

Reviewed by 2 · Jul 18, 2026

Open the Aprocitentan interaction page

One more smart check

Taking Comfrey as Part of a Dietary Supplement Product? Check It for Interactions

We hold 29 real supplement products containing Comfrey, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Comfrey. Your product may carry other ingredients that interact with Aprocitentan too, on top of Comfrey — 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 Comfrey and Aprocitentan 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 Comfrey
Top half

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

29 days ago today
Medication Aprocitentan
Top 25%

#594 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 Comfrey

What is Comfrey?

Comfrey
  • Bruises and sprains
  • Muscle and joint pain
  • Minor wounds and skin irritation
  • Back pain
  • Inflammation

Comfrey is a traditional herb used mainly on the skin for bruises, sprains, and joint pain, and some topical products show modest benefit for these uses. However, comfrey contains compounds that can seriously damage the liver, so it should never be taken by mouth and should only be used on unbroken skin for short periods. Pregnant or breastfeeding people should avoid it entirely.

Read the full Comfrey monograph & all interactions
Medication

About Aprocitentan

What Is Aprocitentan Used For?

Brand name: Tryvio

Tryvio is used to treat high blood pressure (hypertension) in adults. It is specifically for people whose blood pressure is not adequately controlled on other blood pressure medications — it is always used together with at least one other antihypertensive drug, not on its own.

Lowering blood pressure helps reduce the risk of serious cardiovascular events such as stroke and heart attack. Tryvio has not been studied as a standalone treatment and is not intended to replace other blood pressure medicines.

See full Aprocitentan drug information
Keep checking

Other Drugs & Comfrey

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

0Major
437Moderate
0Minor
2,392No known interaction
437 Moderate 2,392 No interaction
Moderate

437 interactions

Showing 60 of 437 moderate interactions — see all 437 on the Comfrey page.

No interaction 2,392 drugs checked — show the list

We also checked Comfrey against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,392 medications checked with no known interaction — see the full Comfrey list.

See the full Comfrey interactions page
See every supplement checked against Aprocitentan, 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
Comfrey monograph › Uses, safety, and every drug interaction in one place Aprocitentan supplement interactions › Every supplement checked against Aprocitentan, ranked by severity Aprocitentan 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 Comfrey and Aprocitentan Together: Common Questions

Can you take Comfrey with Aprocitentan?
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 Comfrey and Aprocitentan?
Aprocitentan belongs to more than one drug category, and Comfrey 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 Comfrey and Aprocitentan 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 Aprocitentan and Comfrey?

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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.