Drug & supplement interaction

Grape + Macitentan

Macitentan brand name: Opsumit.

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

Grape has a moderate interaction with Macitentan. It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.

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

Grape and Macitentan

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Macitentan

Macitentan falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Grape interacts with.

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not 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

Here's the situation with grape seed extract and your Opsumit (macitentan). Your body uses an enzyme called CYP3A4 to break this medication down, and lab studies hint that concentrated grape seed extract might bump into that same enzyme. The tricky part is that the research pulls in two directions: some test-tube studies suggest it could slow the enzyme (which could let macitentan build up and raise the odds of side effects like headache, swelling in the ankles, low blood pressure, or anemia), while animal studies suggest it could speed up the enzyme (which could weaken how well your PAH is controlled).

So far none of this has actually shown up in people, and eating grapes or drinking grape juice is not a concern. If you're thinking about a grape seed supplement, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  2. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu

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

Grape Also Interacts With Other Medications

Grape has 869 moderate, 42 minor known drug interactions in our database — the Macitentan one above is one of them. If you take anything else, check it against the full list below.

Moderate 869 Minor 42 No known interaction 1,919 (incl. Macitentan)
Taking anything else?

Check Another of Your Medications Against Grape

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

From our Q&A

Questions About Grape or Macitentan

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

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Macitentan page lists 253 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: 9 major · 205 moderate · 39 minor.

From our pharmacist’s overview on the Macitentan page

“If you take macitentan (Opsumit) for pulmonary arterial hypertension, study this page rather than skim it. It lists 253 supplement and herbal ingredients, nine rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Macitentan interaction page

One more smart check

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

We hold 8,053 real supplement products containing Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grape. Your product may carry other ingredients that interact with Macitentan too, on top of Grape — 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 Grape and Macitentan 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 Grape
Top 5%

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

29 days ago today
Medication Macitentan
Top 25%

#352 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 Grape

What is Grape?

Grape
  • Antioxidant support
  • Heart and circulation health
  • Vein problems (such as varicose veins)
  • Eye health
  • General anti-inflammatory support

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is healthy and generally safe, the supplement evidence for treating specific conditions is mostly limited or preliminary. Talk with your pharmacist or doctor before starting a grape supplement.

Read the full Grape monograph & all interactions
Medication

About Macitentan

What Is Macitentan Used For?

Brand name: Opsumit

Macitentan tablets — sold under the brand name Opsumit — are used to treat pulmonary arterial hypertension (PAH, WHO Group I), a type of high blood pressure in the arteries of the lungs. The goal is to slow the disease from getting worse and to lower the chance of being hospitalized because of PAH.

In the key clinical study, macitentan was used in adults with mainly moderate-to-severe PAH symptoms. Patients had PAH caused by unknown or inherited causes, connective tissue disorders, or congenital heart disease with repaired shunts.

See full Macitentan drug information
Keep checking

Other Drugs & Grape

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

0Major
869Moderate
42Minor
1,918No known interaction
869 Moderate 42 Minor 1,918 No interaction
Moderate

869 interactions

Showing 60 of 869 moderate interactions — see all 869 on the Grape page.

Minor

42 interactions

No interaction 1,918 drugs checked — show the list

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

Showing the 60 most looked-up of 1,918 medications checked with no known interaction — see the full Grape list.

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

Can you take Grape with Macitentan?
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.
How serious is the Grape and Macitentan 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 and Grape?

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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.