Drug & supplement interaction

Sage + 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 Sage can interact with; the most serious is rated moderate. Theoretically, sage might increase or decrease the effects of antihypertensive drugs.

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

Sage and Macitentan, Tadalafil

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

Why Are There 3 Interactions?

Sage interacts with whole categories of medication. Macitentan, Tadalafil falls into 3 of those categories, so it can interact with Sage in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTIHYPERTENSIVE DRUGS

1 of 3

Why this applies to Macitentan, Tadalafil

Macitentan, Tadalafil falls under ANTIHYPERTENSIVE DRUGS — the group Sage interacts with.

Theoretically, sage might increase or decrease the effects of antihypertensive drugs.
Animal research suggests that common sage (Salvia officinalis) can cause prolonged blood pressure reduction. However, clinical research suggests that Spanish sage (Salvia lavandulaefolia) can increase blood pressure in some people with hypertension. Until more is known, use with caution.
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 medicines, macitentan and tadalafil, that both work to relax blood vessels and lower pressure in the lungs and body. That means your blood pressure is already being nudged downward on purpose. Sage is a wildcard here. Lab and animal studies hint it might lower blood pressure further, while other research on Spanish sage suggests it could actually raise it in some people. In short, we honestly don't know which way it will push.

This is theoretical and based on weak (lab/animal) evidence, so please don't panic. Sprinkling sage on your dinner is very unlikely to matter. Concentrated sage extracts or capsules are the real question. If your blood pressure runs low, dizziness, lightheadedness, or headache could get worse. Chat with your pharmacist or doctor before adding a sage supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Todorov S, Philianos S, Petkov V, et al. Experimental pharmacological study of three species from genus Salvia. Acta Physiol Pharmacol (Bulg) 1984;10:13-20.
  2. Perry NS, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 2003;75:651-9.. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

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

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9. So far, this interaction has 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

Opsynvi is a combo pill of macitentan and tadalafil, both used to treat pulmonary arterial hypertension (high blood pressure in the lungs). The idea here is that sage, in lab dishes, can slow down a liver enzyme called CYP2C9 that helps clear these medicines. If that same effect happened in people, the drugs could build up a bit and their blood-pressure-lowering action could get stronger.

Practically, that might mean more dizziness, headache, flushing, low blood pressure, or swelling. But I want to be honest with you: this is only a theoretical concern from test-tube studies, and it has never actually been reported in humans. A little sage in your cooking is very unlikely to matter. Concentrated sage extracts or the essential oil are where I'd be more cautious, so please run those by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4. So far, this interaction has 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

Opsynvi combines two medicines, macitentan and tadalafil, and both are handled in part by a liver enzyme called CYP3A4. In lab (test tube) studies, sage extracts appear to slow that enzyme down a bit. If that happened in the body, these drugs could clear a little more slowly and build up, which might nudge up their usual effects like low blood pressure, dizziness, headache, flushing, a stuffy nose, or leg swelling.

Here's the honest part: this is only a theoretical concern from laboratory work, and it hasn't actually been reported in people. Everyday cooking amounts of sage are very unlikely to matter. Concentrated sage extracts or the essential oil are a different story. Before adding a sage supplement, run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  2. Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.

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

Sage Also Interacts With Other Medications

Sage has 1,295 moderate 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 1,295 No known interaction 1,535 (incl. Macitentan, Tadalafil)
Taking anything else?

Check Another of Your Medications Against Sage

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

Everything else you take

See Every Supplement That Interacts With Macitentan, Tadalafil

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

We hold 718 real supplement products containing Sage, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sage. Your product may carry other ingredients that interact with Macitentan, Tadalafil too, on top of Sage — 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 Sage 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 Sage
Top 25%

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

29 days ago today
Medication Macitentan, Tadalafil
Top half

#1,321 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 Sage

What is Sage?

Sage
  • Sore throat and mouth irritation
  • Digestive upset
  • Excessive sweating
  • Memory and thinking
  • Menopause symptoms (hot flashes)
  • General antioxidant support

Sage is a common kitchen herb that is generally safe in food amounts and is traditionally used for sore throats, digestion, sweating, and memory. Some early research is encouraging for sore throat and menopausal hot flashes, but most uses are not well proven. Concentrated extracts and the essential oil should be used carefully because high doses contain a compound called thujone, which can be harmful.

Read the full Sage monograph & all interactions
Keep checking

Other Drugs & Sage

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

0Major
1,295Moderate
0Minor
1,534No known interaction
1,295 Moderate 1,534 No interaction
Moderate

1,295 interactions

Showing 60 of 1,295 moderate interactions — see all 1,295 on the Sage page.

No interaction 1,534 drugs checked — show the list

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

Showing the 60 most looked-up of 1,534 medications checked with no known interaction — see the full Sage list.

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

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