Drug & supplement interaction

Adrafinil + Perampanel

Perampanel brand name: Fycompa.

Moderate Interaction
The bottom line Moderate

Perampanel falls into 4 drug categories that Adrafinil can interact with; the most serious is rated moderate. Theoretically, adrafinil might increase the levels and clinical effects of CYP2C19 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Adrafinil and Perampanel

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Adrafinil interacts with whole categories of medication. Perampanel falls into 4 of those categories, so it can interact with Adrafinil in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

1 of 4

Why this applies to Perampanel

Perampanel falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES — the group Adrafinil interacts with.

Theoretically, adrafinil might increase the levels and clinical effects of CYP2C19 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to inhibit CYP2C19 activity 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 of it. When your body turns adrafinil into modafinil, that modafinil can gently slow down a liver enzyme called CYP2C19, which is one of the pathways that helps clear perampanel. If that pathway slows, perampanel can linger and build up a bit more than usual. Perampanel is your seizure medication (not a prodrug), so higher levels mean stronger effects from the drug itself.

In real life, that could show up as more drowsiness, dizziness, trouble walking steadily, irritability, or mood changes, which are perampanel's usual side effects. I want to be honest though: this is a theoretical concern based on lab data, not proven in people. Still, since both can affect alertness and the liver, please run this by your doctor or pharmacist before combining them.

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
  3. Provigil (modafinil) [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc. Published: January 2015. Accessed on: Nov 11, 2022.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 4

Perampanel also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, adrafinil might reduce the levels and clinical effects of CYP1A2 substrates.
Adrafinil is a precursor to the stimulant prescription drug modafinil. Modafinil has been shown to weakly induce CYP1A2 activity 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 thinking on combining adrafinil with Perampanel (Fycompa). Once your liver turns adrafinil into modafinil, that modafinil may gently speed up an enzyme called CYP1A2, which is one of the pathways your body uses to clear perampanel. If that enzyme works faster, perampanel could be cleared a bit quicker, leaving lower levels in your system. In plain terms, that could mean your seizure medicine works less well, which is a real concern when you're relying on it to prevent seizures.

I want to be honest about the strength here: this is theoretical, based only on lab data showing modafinil weakly nudges that enzyme. It hasn't been proven in people. Still, since missed seizure control matters a lot, please run this by your doctor or pharmacist before mixing them.

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
  3. 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

3 of 4

Perampanel 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 situation if you're thinking about pairing Adrafinil with Perampanel (Fycompa). Once your liver turns adrafinil into modafinil, that modafinil may slow down a liver enzyme called CYP2C9, which is one of the pathways your body uses to clear perampanel. If perampanel gets cleared more slowly, it can build up, and that can mean stronger effects and more side effects like dizziness, sleepiness, trouble walking, and mood or behavior changes.

I want to be honest about the strength of this: it's theoretical, based on lab data rather than real patient cases, so it may never cause a noticeable problem. Still, since perampanel already affects alertness and balance, please run this combination by your doctor or pharmacist before mixing them.

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

4 of 4

Perampanel 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

Here's the gist for Fycompa (perampanel). Your liver uses an enzyme called CYP3A4 to clear this seizure medicine. Adrafinil turns into modafinil in your body, and modafinil can gently speed up that same enzyme. In theory, that could clear perampanel a little faster and lower its level, which might mean it works less well at holding your seizures in check.

I want to be honest though: this is a theoretical concern based on how these drugs behave, not something proven in real patients. Still, because seizure control is too important to gamble with, please loop in your doctor or pharmacist before mixing these. Don't change your perampanel dose on your own.

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 Perampanel one above is among 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 Perampanel

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Perampanel page lists 230 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 9 major · 175 moderate · 46 minor.

From our pharmacist’s overview on the Perampanel page

“Perampanel (Fycompa) is a seizure medicine that already causes drowsiness and dizziness on its own, which is why I treat this list of 230 interacting supplements with real care. Most entries do one of two things: they add to its sedating effect, as alcohol and kava do, or they change how the liver handles it.”

Reviewed by 2 · Jul 18, 2026

Open the Perampanel 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 Perampanel 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 Perampanel 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

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

29 days ago today
Medication Perampanel
Steady interest

#1,551 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 Perampanel

What Is Perampanel Used For?

Brand name: Fycompa

Perampanel — available as Fycompa and in generic forms — is used to treat partial-onset seizures (seizures that start in one area of the brain) in patients with epilepsy aged 4 years and older. Both the tablet and oral suspension forms carry this indication.

Perampanel tablets and oral suspension are also approved as add-on (adjunctive) therapy for primary generalized tonic-clonic seizures (grand mal seizures involving the whole brain at once) in patients with epilepsy aged 12 years and older. Fycompa oral suspension and tablet share both indications.

See full Perampanel 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
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
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 Perampanel Together: Common Questions

Can you take Adrafinil with Perampanel?
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 4 interactions listed for Adrafinil and Perampanel?
Perampanel 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 Perampanel 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.