Drug & supplement interaction

Apple + Bosentan

Bosentan brand name: Tracleer.

Major Interaction
The bottom line Major

Bosentan falls into 2 drug categories that Apple can interact with; the most serious is rated major. Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.

Read the full interaction report
SeverityMajor
LikelihoodLikely
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Apple and Bosentan

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

Why Are There 2 Interactions?

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

Major

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

1 of 2

Why this applies to Bosentan

Bosentan falls under ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) — the group Apple interacts with.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.
Research shows that consuming apple juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP. Fexofenadine, atenolol, and aliskiren are substrates of OATP. Clinical research shows that coadministration of apple juice decreases bioavailability of fexofenadine by up to 78%, aliskiren by 63%, and atenolol by up to 82%. These effects appear to increase with larger quantities of apple juice. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.
Severity Major Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: bosentan gets carried into your body partly by a transporter called OATP, and the polyphenols in apple juice can temporarily block that doorway. When the doorway is blocked, less of the medicine actually gets absorbed, so your blood levels can drop. With bosentan, that's a concern because you're relying on steady levels to keep the blood vessels in your lungs relaxed. Lower levels could mean less benefit, and you might notice more shortness of breath or trouble keeping up with activity over time.

This was studied mostly with larger amounts of apple juice, not a single apple as food. A practical tip is to separate them by at least a few hours, but please run your routine by your pharmacist or doctor before changing anything.

References
  1. Bailey DG, Dresser GK, Munoz C, et al. Reduction of fexofenadine bioavailability by fruit juices. Clin Pharmacol Ther 2001;69:P21.
  2. Greenblatt DJ. Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides. J Clin Pharmacol 2009;49:1403-7. PubMed
  3. Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol 2010;70:645-55. PubMed
  4. Kamath AV, Yao M, Zhang Y, Chong S. Effect of fruit juices on the oral bioavailability of fexofenadine in rats. J Pharm Sci 2005;94:233-9. PubMed
  5. Tapaninen T, Neuvonen PJ, Niemi M. Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren. Br J Clin Pharmacol 2011;71:718-26. PubMed
  6. Jeon H, Jang IJ, Lee S, et al. Apple juice greatly reduces systemic exposure to atenolol. Br J Clin Pharmacol 2012 May 11. doi: 10.1111/j.1365-2125.2012.04324.x. [Epub ahead of print]. PubMed
  7. Akamine Y, Miura M, Komori H, et al. Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers. Eur J Clin Pharmacol. 2014 Sep;70(9):1087-95. PubMed
Moderate

ANTIHYPERTENSIVE DRUGS

2 of 2

Bosentan also falls under ANTIHYPERTENSIVE DRUGS.

Consuming apple juice with antihypertensive drugs might interfere with blood pressure control.
Some clinical evidence suggests that consuming apple and cherry juice can increase blood pressure in elderly patients.
Severity Moderate Likelihood Probable Evidence B

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version for anyone taking bosentan (Tracleer) for pulmonary arterial hypertension. The concern on file isn't about bosentan being broken down differently. It's simpler than that: some lower-quality research found that drinking apple juice (and cherry juice) raised blood pressure a bit in older adults. Since bosentan is part of your plan to keep the blood vessels in your lungs relaxed, anything that nudges blood pressure up could work against that goal.

Don't panic, though. Eating a whole apple as food is very unlikely to cause trouble. This caution is really about regularly drinking lots of apple juice. If that's a daily habit for you, it's worth mentioning to your pharmacist or doctor so they can keep an eye on your readings.

References
  1. Visvanathan, R., Chen, R., Horowitz, M., and Chapman, I. Blood pressure responses in healthy older people to 50 g carbohydrate drinks with differing glycaemic effects. Br J Nutr 2004;92(2):335-340. 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

Apple Also Interacts With Other Medications

Apple has 46 major, 253 moderate 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 Apple

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

From our Q&A

Questions About Apple 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 Apple 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 Apple 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), Beer (major) and Grapefruit (major).

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

Open the Bosentan interaction page

One more smart check

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

We hold 2,841 real supplement products containing Apple, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Apple. Your product may carry other ingredients that interact with Bosentan too, on top of Apple — 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 Apple 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 Apple
Top 10%

#105 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 Apple

What is Apple?

Apple
  • General nutrition and fiber intake
  • Heart and cholesterol health
  • Blood sugar and weight management
  • Digestive regularity
  • Antioxidant support

Apples are a nutritious whole food that provides fiber, vitamins, and antioxidant plant compounds, and eating them regularly fits well into a healthy diet. While research suggests apples may support heart and digestive health, most claims about concentrated apple supplements or extracts are not strongly proven, so enjoy apples as food and talk with your pharmacist before using high-dose products.

Read the full Apple 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 & Apple

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

46Major
253Moderate
0Minor
2,530No known interaction
Major

46 interactions

Moderate

253 interactions

Showing 60 of 253 moderate interactions — see all 253 on the Apple page.

No interaction 2,530 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 Apple and Bosentan Together: Common Questions

Can you take Apple with Bosentan?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Apple and Bosentan?
Bosentan belongs to more than one drug category, and Apple 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 Apple and Bosentan interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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.