Drug & supplement interaction

Cranberry + Macitentan, Tadalafil

Macitentan, Tadalafil brand name: Opsynvi.

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

Macitentan, Tadalafil falls into 2 drug categories that Cranberry can interact with; the most serious is rated moderate. Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.

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

Cranberry and Macitentan, Tadalafil

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

Why Are There 2 Interactions?

Cranberry interacts with whole categories of medication. Macitentan, Tadalafil falls into 2 of those categories, so it can interact with Cranberry 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 Macitentan, Tadalafil

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

Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.
A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control.
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 active medicines, macitentan and tadalafil, and both are cleared by a liver enzyme called CYP3A4. In theory, cranberry may slow that enzyme a little, which could let these drugs build up somewhat. If levels rise, you might notice more of their usual effects, like headache, flushing, stuffy nose, low blood pressure, dizziness, or swelling in the legs.

Honestly though, the evidence here is thin. It comes from one case report with a different drug and some animal data, so it is more of a theoretical concern than a proven problem. Occasional cranberry, or a normal glass of juice, is unlikely to cause trouble. If you plan to use concentrated cranberry supplements daily, just run it by your pharmacist or doctor first so they can keep an eye on things.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Uesawa, Y. and Mohri, K. Effects of cranberry juice on nifedipine pharmacokinetics in rats. J Pharm Pharmacol 2006;58(8):1067-1072. PubMed
  2. Doad GJ, Kabange W. Cranberry juice, atorvastatin and back pain. J Med Assoc Ga 2014;103(1):14.
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

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

Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.
There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes. However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac. Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate. Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin.
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

Good question about pairing cranberry with Opsynvi (the macitentan and tadalafil combo). The idea here is that plant compounds in cranberry might slow down a liver enzyme called CYP2C9 that helps clear these medicines. If that happened, drug levels could creep up a bit, and you might notice more of Opsynvi's usual effects like low blood pressure, dizziness, flushing, headache, or leg swelling.

Here's the reassuring part: this is mostly a theory from lab dishes, not real people. When researchers actually tested cranberry against similar drugs, they found little to no meaningful change. Everyday cranberry juice or a supplement is unlikely to cause trouble. Still, since Opsynvi affects blood pressure, mention it to your pharmacist or doctor if you use cranberry regularly.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Anon. Possible interaction between warfarin and cranberry juice. Current Problems in Pharmacovigilance 2003;29:8. PubMed
  2. 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
  3. Hodek P, Trefil P, Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 2002;139:1-21.. PubMed
  4. Li Z, Seeram NP, Carpenter CL, et al. Cranberry does not affect prothrombin time in male subjects on warfarin. J Am Diet Assoc 2006;106:2057-61. PubMed
  5. Lilja JJ, Backman JT, Neuvonen PJ. Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam - probes of CYP2C9, CYP1A2 and CYP3A4. Clin Pharmacol The 2007:81:833-9. PubMed
  6. Ushijima K, Tsuruoka S, Tsuda H, Hasegawa G, Obi Y, Kaneda T, Takahashi M, Maekawa T, Sasaki T, Koshimizu TA, Fujimura A. Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects. Br J Clin Pharmaco 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

Cranberry Also Interacts With Other Medications

Cranberry has 642 moderate, 69 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 642 Minor 69 No known interaction 2,119 (incl. Macitentan, Tadalafil)
Taking anything else?

Check Another of Your Medications Against Cranberry

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

From our Q&A

Questions About Cranberry 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 Cranberry 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 Cranberry 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 Cranberry as Part of a Dietary Supplement Product? Check It for Interactions

We hold 5,249 real supplement products containing Cranberry, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cranberry. Your product may carry other ingredients that interact with Macitentan, Tadalafil too, on top of Cranberry — 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 Cranberry 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 Cranberry
Top 5%

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

29 days ago today
Medication Macitentan, Tadalafil
Top half

#1,293 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 Cranberry

What is Cranberry?

Cranberry
  • Urinary tract infection prevention
  • Bladder health
  • Antioxidant support
  • Source of vitamin C

Cranberry is best known for helping to prevent repeated urinary tract infections (UTIs) in some people, and the evidence here is moderate but mixed. It is not a reliable treatment for an active UTI, which usually needs antibiotics. For most people cranberry products are well tolerated, but check with a pharmacist before relying on them, especially if you have frequent infections.

Read the full Cranberry monograph & all interactions
Keep checking

Other Drugs & Cranberry

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

0Major
642Moderate
69Minor
2,118No known interaction
642 Moderate 69 Minor 2,118 No interaction
Moderate

642 interactions

Showing 60 of 642 moderate interactions — see all 642 on the Cranberry page.

Minor

69 interactions

Showing 60 of 69 minor interactions — see all 69 on the Cranberry page.

No interaction 2,118 drugs checked — show the list

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

Showing the 60 most looked-up of 2,118 medications checked with no known interaction — see the full Cranberry list.

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

Can you take Cranberry 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 2 interactions listed for Cranberry and Macitentan, Tadalafil?
Macitentan, Tadalafil belongs to more than one drug category, and Cranberry 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 Cranberry 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 Cranberry?

Our pharmacists answer your medication & supplement questions — free.

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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.