Drug & supplement interaction

Adrafinil + Trofinetide

Trofinetide brand name: Daybue.

Moderate Interaction
The bottom line Moderate

Adrafinil has a moderate interaction with Trofinetide. Theoretically, drugs that inhibit CYP3A4 might increase the levels and clinical effects of adrafinil.

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

Adrafinil and Trofinetide

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

Why this applies to Trofinetide

Trofinetide falls under CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS — the group Adrafinil interacts with.

Theoretically, drugs that inhibit CYP3A4 might increase the levels and clinical effects of adrafinil.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil is metabolized by CYP3A4.
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 how these two fit together. Adrafinil is a prodrug: your liver turns it into modafinil, and that modafinil is cleared partly by a liver enzyme called CYP3A4. Trofinetide (Daybue) is thought to gently slow that same enzyme. In theory, if you slow the breakdown of modafinil, more of it can hang around, which could mean stronger effects like trouble sleeping, jitteriness, a faster heartbeat, headache, or anxiety.

I want to be honest about the strength of this concern. This is a theoretical interaction based on how the drugs work, not on real patient reports. Still, adrafinil is unregulated and hard on the liver on its own. Before combining it with trofinetide, please check with your doctor or pharmacist first.

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, 1,057 moderate known drug interactions in our database — the Trofinetide one above is one of them. If you take anything else, check it against the full list below.

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 Trofinetide

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Trofinetide page lists 30 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Cannabidiol (cbd) (moderate), Cannabinol (cbn) (moderate), Cannabis (moderate) and Coffee Charcoal (moderate).

By severity: 1 major · 19 moderate · 10 minor.

From our pharmacist’s overview on the Trofinetide page

“Families managing Rett syndrome often add supplements alongside trofinetide (Daybue), and this is a list that deserves real care rather than a quick skim. The interactions fall into two patterns.”

Reviewed by 2 · Jul 18, 2026

Open the Trofinetide 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 Trofinetide 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 Trofinetide 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

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

29 days ago today
Medication Trofinetide
Top half

#1,341 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 Trofinetide

What Is Trofinetide Used For?

Brand name: Daybue

Trofinetide treats Rett syndrome in adults and pediatric patients 2 years of age and older.

It is sold as Daybue (oral solution) and Daybue Stix (powder that is dissolved in liquid to make an oral solution). Both carry this same use.

See full Trofinetide 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
1,057Moderate
0Minor
1,771No known interaction
Major

1 interaction

Moderate

1,057 interactions

Showing 60 of 1,057 moderate interactions — see all 1,057 on the Adrafinil page.

No interaction 1,771 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 1,771 medications checked with no known interaction — see the full Adrafinil 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 Adrafinil and Trofinetide Together: Common Questions

Can you take Adrafinil with Trofinetide?
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.
How serious is the Adrafinil and Trofinetide 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 Trofinetide 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.