Drug & supplement interaction

Adrafinil + 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 Adrafinil can interact with; the most serious is rated moderate. Theoretically, adrafinil might reduce 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

Adrafinil and Macitentan, Tadalafil

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

Why Are There 3 Interactions?

Adrafinil interacts with whole categories of medication. Macitentan, Tadalafil falls into 3 of those categories, so it can interact with Adrafinil 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 Adrafinil interacts with.

Theoretically, adrafinil might reduce the effects of antihypertensive drugs.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to increase diastolic and systolic blood pressure. Retrospective analyses show that patients taking modafinil had a small but increased rate of requiring new antihypertensive drugs or increased use of antihypertensive drugs when compared with placebo.
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 Opsynvi (the combination of macitentan and tadalafil). This medicine is prescribed to lower the pressure in the blood vessels of your lungs, and it also gently relaxes blood vessels overall. Adrafinil, on the other hand, turns into modafinil in your liver, and modafinil has been shown to nudge blood pressure up a bit in some people.

So the concern is that adrafinil could work against what your Opsynvi is trying to do, possibly making it a little less effective. To be clear, this is a theoretical concern based on how these drugs behave, not something proven for this exact pairing, so I wouldn't panic. Still, since Opsynvi is treating a serious condition, please check with your doctor or pharmacist before combining them, and keep an eye on your blood pressure if you do.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

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

Theoretically, adrafinil might increase the levels and clinical effects of CYP2C9 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to reduce CYP2C9 expression in vitro.
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 CYP2C9. The idea here is that adrafinil (which your body turns into modafinil) may slow that enzyme down. If that happens, these two drugs could clear a bit slower and build up in your system, nudging their effects and side effects upward.

In real terms, that could mean more low blood pressure, dizziness, headache, flushing, or leg swelling. I'll be honest with you though: this is a theoretical concern based on lab data, not confirmed in people, so it may not amount to much. Still, since blood pressure is already the target here, please loop in your doctor or pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
  2. Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68(13):1803-39. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

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

Theoretically, adrafanil might reduce levels and clinical effects of CYP3A4 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP3A4 activity.
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, and it's used to treat pulmonary arterial hypertension (high blood pressure in the lungs). Both of these medicines are broken down by a liver enzyme called CYP3A4. Here's the concern: adrafinil turns into modafinil in your body, and modafinil can gently speed up that enzyme. If it does, your body may clear these drugs a bit faster, so you could get less benefit than expected.

With a serious condition like pulmonary hypertension, you don't want your treatment quietly losing strength. That said, this is only a theoretical concern based on how the drugs work, and modafinil is only a weak enzyme booster. Please don't change anything on your own. Just loop in your doctor or pharmacist before combining these.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Urban AE, Cubala WJ. The role of eugeroics in the treatment of affective disorders. Psychiatr Pol. 2020;54(1):21-33. PubMed
  2. Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.

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

Adrafinil Also Interacts With Other Medications

Adrafinil has 1 major, 1,055 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.

Major 1 Moderate 1,055 No known interaction 1,774 (incl. Macitentan, Tadalafil)
Taking anything else?

Check Another of Your Medications Against Adrafinil

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

Everything else you take

See Every Supplement That Interacts With Macitentan, Tadalafil

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

We hold 7 real supplement products containing Adrafinil, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Adrafinil. Your product may carry other ingredients that interact with Macitentan, Tadalafil too, on top of Adrafinil — 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 Adrafinil 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 Adrafinil
Top half

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

29 days ago today
Medication Macitentan, Tadalafil
Top 25%

#534 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 Adrafinil

What is Adrafinil?

Adrafinil
  • Wakefulness and alertness
  • Fatigue
  • Focus and concentration
  • Cognitive enhancement (nootropic)
  • Daytime sleepiness

Adrafinil is a synthetic compound that the body converts into modafinil, a prescription wakefulness-promoting drug. It is sometimes sold as a nootropic supplement, but it is unregulated, carries real risks (especially to the liver), and is banned in some sports and countries. Talk with a doctor or pharmacist before using it.

Read the full Adrafinil monograph & all interactions
Keep checking

Other Drugs & Adrafinil

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

1Major
1,055Moderate
0Minor
1,773No known interaction
1 Major 1,055 Moderate 1,773 No interaction
Major

1 interaction

Moderate

1,055 interactions

Showing 60 of 1,055 moderate interactions — see all 1,055 on the Adrafinil page.

No interaction 1,773 drugs checked — show the list

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

Showing the 60 most looked-up of 1,773 medications checked with no known interaction — see the full Adrafinil list.

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

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