Drug & supplement interaction

Adrafinil + Sacubitril, Valsartan

Sacubitril, Valsartan brand name: Entresto.

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

Sacubitril, Valsartan falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Adrafinil and Sacubitril, Valsartan

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

Why Are There 2 Interactions?

Adrafinil interacts with whole categories of medication. Sacubitril, Valsartan falls into 2 of those categories, so it can interact with Adrafinil in 2 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 2

Why this applies to Sacubitril, Valsartan

Sacubitril, Valsartan 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 gist: Entresto (sacubitril/valsartan) is a heart failure medicine that also lowers your blood pressure. Adrafinil turns into modafinil in your body, and modafinil tends to nudge blood pressure up a bit. So the worry is that adrafinil could push against the work Entresto is doing, making it a little less effective at controlling your numbers.

I want to be honest about how strong this concern is: it's theoretical, based on how these drugs behave rather than solid head-to-head studies. The blood pressure bump seen with modafinil was usually small. Still, with heart failure you don't want surprises, so please loop in your doctor or pharmacist before adding adrafinil, 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 2

Sacubitril, Valsartan 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

Here's the gist with Entresto (sacubitril/valsartan) and adrafinil. Your body turns adrafinil into modafinil, and lab studies hint that modafinil may slow down a liver enzyme called CYP2C9. Since the valsartan part of Entresto is cleared partly by that enzyme, the theory is that valsartan could build up a bit and act stronger than expected.

If that happened, you might see lower blood pressure, dizziness, lightheadedness when standing up, or in some cases rising potassium. I want to be honest, though: this is a theoretical concern based only on test-tube data, not real patient reports, so it may never cause a problem. Still, because Entresto is a heart medicine and adrafinil is unregulated and hard on the liver, please run this by 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

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 Sacubitril, Valsartan 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. Sacubitril, Valsartan)
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 Sacubitril, Valsartan

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sacubitril, Valsartan page lists 249 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), Lithium (major) and Oleander (major).

By severity: 7 major · 206 moderate · 36 minor.

From our pharmacist’s overview on the Sacubitril, Valsartan page

“Entresto (sacubitril and valsartan) is a heart failure medicine, and heart failure patients tend to be heavy supplement users, reaching for fish oil, potassium, and herbal blood-pressure remedies. That instinct carries real risk here.”

Reviewed by 2 · Jul 18, 2026

Open the Sacubitril, Valsartan 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 Sacubitril, Valsartan 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 Sacubitril, Valsartan 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

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

29 days ago today
Medication Sacubitril, Valsartan
Top 10%

#146 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
Medication

About Valsartan and Sacubitril

What Is Valsartan and Sacubitril Used For?

Brand name: Entresto

Sacubitril and valsartan is used to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. The benefit is most clearly seen in patients whose heart pumps with a lower-than-normal ejection fraction (the percentage of blood the heart pushes out with each beat).

It is also approved to treat symptomatic heart failure with reduced left ventricular function in children aged 1 year and older. In pediatric patients, it lowers a blood marker of heart stress (NT-proBNP) and is expected to improve heart outcomes.

See full Valsartan and Sacubitril drug information
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 Sacubitril, Valsartan, 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 Sacubitril, Valsartan supplement interactions › Every supplement checked against Sacubitril, Valsartan, ranked by severity Valsartan and Sacubitril drug information › The full plain-English guide to this medication 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 Sacubitril, Valsartan Together: Common Questions

Can you take Adrafinil with Sacubitril, Valsartan?
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 Adrafinil and Sacubitril, Valsartan?
Sacubitril, Valsartan 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 Sacubitril, Valsartan 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 Sacubitril, Valsartan and Adrafinil?

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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.