Drug & supplement interaction

Kava + Macitentan, Tadalafil

Macitentan, Tadalafil brand name: Opsynvi.

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

Macitentan, Tadalafil falls into 3 drug categories that Kava can interact with; the most serious is rated moderate. Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.

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

Kava and Macitentan, Tadalafil

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

Why Are There 3 Interactions?

Kava interacts with whole categories of medication. Macitentan, Tadalafil falls into 3 of those categories, so it can interact with Kava in 3 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 3

Why this applies to Macitentan, Tadalafil

Macitentan, Tadalafil falls under HEPATOTOXIC DRUGS — the group Kava interacts with.

Theoretically, using kava with hepatotoxic drugs might increase the risk of liver damage.
Kava has been linked with over 100 cases of hepatotoxicity. Most cases occur with excessive and prolonged use. There is some concern that kava can adversely affect the liver, especially when used in combination with hepatotoxic drugs.
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 with Opsynvi (the macitentan and tadalafil combo) and kava. This isn't about kava changing how the medication works or how much of it sits in your body. The concern is that both can be tough on your liver. Macitentan, like other drugs in its class, can raise liver enzymes, and kava has been tied to rare but real cases of liver injury. Stack them together and you may be adding stress to the same organ.

To be fair, this is a theoretical concern based mostly on scattered reports, not strong studies. Still, since your liver is already being watched on this medication, I'd skip kava and check with your doctor or pharmacist first. Watch for yellowing skin or eyes, dark urine, or belly pain.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with Kava, a herbal remedy for anxiety. BMJ 2001;322:139.
  2. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity [letter]. Ann Intern Med 2001;135:68-9.
  3. Liver Toxicity With Kava. Pharmacist's Letter/Prescriber's Letter. January 2001.
  4. Consultation letter MLX 286: Proposals to prohibit the herbal ingredient Kava-Kava (Piper methysticum) in unlicensed medicines. Medicines Control Agency, United Kingdom, July 19, 2002.
  5. Li XZ, Ramzan I. Role of ethanol in kava hepatotoxicity. Phytother Res 2010;24:475-80. PubMed
  6. Chanwai, L. G. Kava toxicity. Emergency Medicine 2002;12:142-145.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Macitentan, Tadalafil also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, kava might increase levels of CYP2C9 substrates.
In vitro research shows that kava significantly inhibits CYP2C9 enzymes. This effect has not yet been reported in humans.
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 blood pressure medicines used for pulmonary arterial hypertension: macitentan and tadalafil. Both are partly cleared by a liver enzyme called CYP2C9. Lab studies (in test tubes, not people) hint that kava may slow that enzyme down. In theory, that could let these drugs build up a bit more than expected.

If that happened, you might notice more of their usual side effects, like low blood pressure, dizziness, headache, flushing, or swelling. I want to be honest though: this is theoretical and hasn't been shown in humans. On top of that, both kava and this medicine can stress the liver, so combining them raises that concern too. Please check with your pharmacist or doctor before pairing them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Macitentan, Tadalafil also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if kava inhibits CYP3AA; research is conflicting.
Although in vitro research suggests that kava inhibits CYP3A4, more robust clinical evidence shows that kava has no effect on CYP3A4. In a clinical study in healthy volunteers, taking kava 1000 mg twice daily (containing a daily dose of 138 mg kavalactones) for 28 days had no effect on CYP3A4 activity.
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

Opsynvi combines two medicines, macitentan and tadalafil, and both are cleared by a liver enzyme called CYP3A4. The concern here is whether kava slows that enzyme down, which could let these drugs build up. In the test tube, kava looked like it might block CYP3A4, but that's the weakest kind of evidence. A better study in healthy people taking a real kava dose for a month found no meaningful effect on this enzyme, so the risk of a true interaction is low.

If levels did rise, you might notice more low blood pressure, dizziness, headache, or flushing. My bigger caution is kava's rare link to liver injury, especially since you're already on two liver-processed drugs. Please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mathews JM, Etheridge AS, Black SR. Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab Dispos 2002;30:1153-7. PubMed
  2. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017;96(2):101-107.

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

Kava Also Interacts With Other Medications

Kava has 248 major, 576 moderate, 341 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.

Major 248 Moderate 576 Minor 341 No known interaction 1,665 (incl. Macitentan, Tadalafil)
Taking anything else?

Check Another of Your Medications Against Kava

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

Everything else you take

See Every Supplement That Interacts With Macitentan, Tadalafil

This page covers Kava 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 Kava as Part of a Dietary Supplement Product? Check It for Interactions

We hold 403 real supplement products containing Kava, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Kava. Your product may carry other ingredients that interact with Macitentan, Tadalafil too, on top of Kava — 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 Kava 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 Kava
Top 25%

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

29 days ago today
Medication Macitentan, Tadalafil
Top half

#1,188 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 Kava

What is Kava?

Kava
  • Anxiety and stress
  • Restlessness
  • Trouble sleeping
  • Relaxation in social or cultural settings
  • Menopausal symptoms

Kava is a Pacific Island plant traditionally used to promote relaxation and ease anxiety, and some studies suggest it may help mild anxiety. However, kava has been linked to rare but serious liver damage, so it should be used with caution, avoided by people with liver problems, and only used after talking with your pharmacist or doctor.

Read the full Kava monograph & all interactions
Keep checking

Other Drugs & Kava

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

248Major
576Moderate
341Minor
1,664No known interaction
248 Major 576 Moderate 341 Minor 1,664 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the Kava page.

Moderate

576 interactions

Showing 60 of 576 moderate interactions — see all 576 on the Kava page.

Minor

341 interactions

Showing 60 of 341 minor interactions — see all 341 on the Kava page.

No interaction 1,664 drugs checked — show the list

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

Showing the 60 most looked-up of 1,664 medications checked with no known interaction — see the full Kava list.

See the full Kava 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
Kava 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 Kava and Macitentan, Tadalafil Together: Common Questions

Can you take Kava 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 Kava and Macitentan, Tadalafil?
Macitentan, Tadalafil belongs to more than one drug category, and Kava 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 Kava 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

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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.