Drug & supplement interaction

Grape + Bosentan

Bosentan brand name: Tracleer.

Moderate Interaction
The bottom line Moderate

Bosentan falls into 2 drug categories that Grape can interact with; the most serious is rated moderate. It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.

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

Grape and Bosentan

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Bosentan

Bosentan 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 deal with grape seed extract and Tracleer (bosentan). Your liver uses an enzyme called CYP3A4 to help clear bosentan from your body. Grape seed extract may bump into that same enzyme, but the research is genuinely mixed: lab studies hint it might slow the enzyme (which could let bosentan build up and increase side effects like headache, flushing, swelling in the legs, or liver strain), while animal studies suggest it might speed up the enzyme (which could make bosentan less effective for your lung pressure).

Honestly, we can't say which way it goes, and so far this hasn't actually been seen in people. It's based only on lab and animal data, so I wouldn't lose sleep over it. Still, since bosentan is a serious medication, check with your pharmacist or doctor before adding a concentrated grape supplement. Eating grapes is fine.

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
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

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

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.
Severity Minor Likelihood Unlikely Evidence D

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

Here's the short version: your body uses a liver enzyme called CYP2C9 to help clear bosentan (Tracleer). In a test tube, compounds from grape seed extract or grape juice looked like they might slow that enzyme down a bit. If that actually happened in people, bosentan could build up slightly, which in theory might mean more of its usual side effects, like headache, flushing, swelling in the legs, or low blood pressure.

But the real-world evidence here is weak. A small human study found that grape juice did not change how the body cleared a similar CYP2C9 drug, so this is mostly lab-based and rated as unlikely and minor. Eating grapes as food shouldn't be a worry. If you're thinking about a concentrated grape seed supplement, just run it by your pharmacist or doctor first.

References
  1. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  2. 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
  3. 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 867 moderate, 42 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 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 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 Grape 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 Grape 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 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 Bosentan 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 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 Grape
Top 5%

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

29 days ago today
Medication Bosentan
Steady interest

#1,685 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 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 & 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
867Moderate
42Minor
1,920No known interaction
Moderate

867 interactions

Showing 60 of 867 moderate interactions — see all 867 on the Grape page.

Minor

42 interactions

No interaction 1,920 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 Grape and Bosentan Together: Common Questions

Can you take Grape 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 2 interactions listed for Grape and Bosentan?
Bosentan belongs to more than one drug category, and Grape 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 Grape 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 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.