Drug & supplement interaction

Licorice + Bosentan

Bosentan brand name: Tracleer.

Moderate Interaction
The bottom line Moderate

Bosentan falls into 3 drug categories that Licorice can interact with; the most serious is rated moderate. Theoretically, licorice might reduce the effects of antihypertensive drugs.

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

Licorice and Bosentan

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Licorice interacts with whole categories of medication. Bosentan falls into 3 of those categories, so it can interact with Licorice in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTIHYPERTENSIVE DRUGS

1 of 3

Why this applies to Bosentan

Bosentan falls under ANTIHYPERTENSIVE DRUGS — the group Licorice interacts with.

Theoretically, licorice might reduce the effects of antihypertensive drugs.
In human research, licorice increases blood pressure in a dose-dependent manner.
Severity Moderate Likelihood Possible Evidence B

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 keep in mind: you take bosentan to relax the blood vessels in your lungs and ease the strain of pulmonary hypertension. Regular licorice (the kind with glycyrrhizin) can push blood pressure up, because it makes your body hold onto sodium and water and lose potassium. So in a real sense, licorice may be working against what bosentan is trying to do.

This concern is largely theoretical and tied to the glycyrrhizin in standard licorice, especially in larger or daily doses. Occasional culinary amounts or DGL (deglycyrrhizinated) products are far less likely to matter. Bosentan is not a prodrug, so this isn't about activation, it's about an opposing effect. Please check with your pharmacist or doctor before using licorice.

References
  1. Sigurjonsdottir HA, Ragnarsson J, Franzson L, Sigurdsson G. Is blood pressure commonly raised by moderate consumption of liquorice? J Hum Hypertens 1995;9:345-8.
  2. Sigurjonsdottir HA, Franzson L, Manhem K, et al. Liquorice-induced rise in blood pressure: a linear dose-response relationship. J Hum Hypertens 2001;15:549-52. PubMed
  3. Koster, M. and David, G. K. Reversible severe hypertension due to licorice ingestion. N Engl J Med 1968;278(25):1381-1383. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Bosentan also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes. However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity. Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.
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 short version: your body uses a liver enzyme called CYP2C9 to help clear Bosentan, and licorice might nudge that enzyme one way or the other. The catch is that the evidence is shaky and conflicting. Some lab studies suggest licorice slows this enzyme (which could let Bosentan build up and raise the risk of side effects like headache, flushing, swelling in the legs, or stress on the liver), while an animal study suggests it speeds the enzyme up (which could make Bosentan less effective at controlling your lung pressure).

Because this is only test-tube and animal data, we honestly can't say which direction wins in real people. A small culinary taste of licorice candy is unlikely to matter, but concentrated supplements over time are a different story. With a medication this important for your lungs, please run any licorice product by your pharmacist or doctor first.

References
  1. Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30:709-15.. PubMed
  2. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  3. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Bosentan also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity. Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity. However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species. Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
Severity Moderate Likelihood Possible Evidence B

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

Your body clears bosentan (Tracleer) using a liver enzyme called CYP3A4, and licorice can nudge that enzyme in either direction depending on the type. Most of the human research suggests licorice tends to speed up CYP3A4, which could lower your bosentan levels and possibly make it work a little less well for your pulmonary hypertension. But one species of licorice may do the opposite and raise levels. Honestly, the data here is limited and mostly theoretical, so we can't say for sure which way it would go for you.

There's a second concern worth mentioning: regular licorice can raise blood pressure and lower potassium, which isn't ideal when you're being treated for PAH. Food or candy amounts are unlikely to matter much, but concentrated supplements could. Please check with your pharmacist or doctor before adding licorice, and don't change your bosentan on your own.

References
  1. Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30:709-15.. PubMed
  2. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  3. Tu, J. H., He, Y. J., Chen, Y., Fan, L., Zhang, W., Tan, Z. R., Huang, Y. F., Guo, D., Hu, D. L., Wang, D., and Hong-Hao Zhou. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol 2010;66(8):805-810. PubMed
  4. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. 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

Licorice Also Interacts With Other Medications

Licorice has 976 moderate, 63 minor known drug interactions in our database — the Bosentan one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Licorice

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

From our Q&A

Questions About Licorice or Bosentan

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Licorice or Bosentan, 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 Bosentan

This page covers Licorice only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Bosentan page lists 266 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), Apple (major) and Beer (major).

By severity: 11 major · 216 moderate · 39 minor.

Open the Bosentan interaction page

One more smart check

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

We hold 4,721 real supplement products containing Licorice, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Licorice. Your product may carry other ingredients that interact with Bosentan too, on top of Licorice — 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 Licorice and Bosentan 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 Licorice
Top 5%

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

29 days ago today
Medication Bosentan
Steady interest

#1,593 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 Licorice

What is Licorice?

Licorice
  • Sore throat and cough
  • Heartburn and stomach upset
  • Mouth ulcers and digestive complaints
  • Inflammation
  • Traditional tonic/adrenal support

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regular licorice contains glycyrrhizin, which can raise blood pressure and lower potassium when taken in large amounts or for a long time, so deglycyrrhizinated (DGL) products are often preferred. Talk to your pharmacist or doctor before using it, especially if you have high blood pressure, heart, or kidney problems.

Read the full Licorice monograph & all interactions
Medication

About Bosentan

What Is Bosentan Used For?

Brand name: Tracleer

Bosentan is used to treat pulmonary arterial hypertension (PAH) — high blood pressure in the arteries of the lungs. In adults, it helps improve the ability to exercise and slows how quickly the disease gets worse.

In children aged 3 years and older with idiopathic (no known cause) or congenital (present from birth) PAH, bosentan is used to lower resistance in the lung blood vessels, which is expected to improve exercise ability. Tracleer is one brand approved for both adults and pediatric patients with PAH.

See full Bosentan drug information
Keep checking

Other Drugs & Licorice

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

0Major
976Moderate
63Minor
1,790No known interaction
Moderate

976 interactions

Showing 60 of 976 moderate interactions — see all 976 on the Licorice page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Licorice page.

No interaction 1,790 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Licorice and Bosentan Together: Common Questions

Can you take Licorice with Bosentan?
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 Licorice and Bosentan?
Bosentan belongs to more than one drug category, and Licorice 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 Licorice and Bosentan 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 Bosentan and Licorice?

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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.