Drug & supplement interaction

Licorice + Macitentan, Tadalafil

Macitentan, Tadalafil brand name: Opsynvi.

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

Macitentan, Tadalafil 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 Macitentan, Tadalafil

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. Macitentan, Tadalafil 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 Macitentan, Tadalafil

Macitentan, Tadalafil 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

Opsynvi is a combo of macitentan and tadalafil that works to relax and widen blood vessels, especially in the lungs, to treat pulmonary arterial hypertension. Here's the catch with licorice: real licorice (the kind with glycyrrhizin) can make your body hold onto salt and water and lose potassium, which tends to push blood pressure up. That's the opposite of what your medicine is trying to do, so licorice could work against it.

This concern is mostly theoretical for this exact drug, and it depends on dose. A little licorice flavoring now and then is unlikely to matter, but regular use or concentrated supplements could blunt your benefit. Deglycyrrhizinated (DGL) products don't carry this issue. Please check with your pharmacist or doctor before using licorice.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Macitentan, Tadalafil 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

Opsynvi combines two medicines: macitentan, which helps relax blood vessels in the lungs, and tadalafil, which does something similar and is also used for erectile issues. Both are handled partly by a liver enzyme called CYP2C9. The concern with licorice here is honestly pretty theoretical. Lab studies hint that licorice might slow this enzyme, while an animal study suggests it might speed it up, so we truly don't know which way it would push.

If licorice slowed things down, these drugs could build up and bring more low blood pressure, headache, flushing, dizziness, or stuffy nose. There's also a separate worry: real licorice (not DGL) can raise blood pressure and drop potassium, which works against what Opsynvi is trying to do. Please loop in your doctor or pharmacist before mixing them.

Contact Dr. Brian directly if you have additional questions on this interaction
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

Macitentan, Tadalafil 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

Opsynvi combines two medicines, macitentan and tadalafil, and both are processed by a liver enzyme called CYP3A4. Here's the tricky part: licorice can pull in both directions on that enzyme depending on the species and product. Some forms may speed the enzyme up (which could lower your levels and weaken the benefit for your pulmonary hypertension), while others may slow it down (which could raise levels and bump up side effects like low blood pressure, headache, flushing, dizziness, or leg swelling).

Honestly, this is mostly theoretical and based on limited data, so I wouldn't panic. But regular licorice also raises blood pressure and drops potassium on its own, which works against what Opsynvi is trying to do. Please check with your pharmacist or doctor before adding any licorice supplement. A deglycyrrhizinated (DGL) product is usually the safer bet.

Contact Dr. Brian directly if you have additional questions on this interaction
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 977 moderate, 63 minor known drug interactions in our database — the Macitentan, Tadalafil one above is among them. If you take anything else, check it against the full list below.

Moderate 977 Minor 63 No known interaction 1,790 (incl. Macitentan, Tadalafil)
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 Macitentan, Tadalafil

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 Macitentan, Tadalafil, 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 Macitentan, Tadalafil

This page covers Licorice only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Macitentan, Tadalafil page lists 264 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 Grapefruit (major).

By severity: 10 major · 215 moderate · 39 minor.

From our pharmacist’s overview on the Macitentan, Tadalafil page

“Opsynvi pairs macitentan and tadalafil to lower pressure in the lung arteries, so anything that drops blood pressure further or shifts how the body handles these drugs deserves genuine respect, and I would read this list carefully. Ten of the 264 ingredients rate major, and most of the rest fall into two camps: additive blood-pressure-…”

Reviewed by 2 · Jul 18, 2026

Open the Macitentan, Tadalafil 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 Macitentan, Tadalafil 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 Macitentan, Tadalafil 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%

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

29 days ago today
Medication Macitentan, Tadalafil
Top 25%

#576 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
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
977Moderate
63Minor
1,789No known interaction
977 Moderate 63 Minor 1,789 No interaction
Moderate

977 interactions

Showing 60 of 977 moderate interactions — see all 977 on the Licorice page.

Minor

63 interactions

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

No interaction 1,789 drugs checked — show the list

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

Showing the 60 most looked-up of 1,789 medications checked with no known interaction — see the full Licorice list.

See the full Licorice interactions page
See every supplement checked against Macitentan, Tadalafil, 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
Licorice monograph › Uses, safety, and every drug interaction in one place Macitentan, Tadalafil supplement interactions › Every supplement checked against Macitentan, Tadalafil, 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 Licorice and Macitentan, Tadalafil Together: Common Questions

Can you take Licorice with Macitentan, Tadalafil?
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 Macitentan, Tadalafil?
Macitentan, Tadalafil 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 Macitentan, Tadalafil 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 Macitentan, Tadalafil 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.