Drug & supplement interaction

Adrafinil + Diazepam

Diazepam brand names: Valium, Valium injection, Diastat AcuDial, Valtoco.

Moderate Interaction
The bottom line Moderate

Diazepam 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 Diazepam

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. Diazepam 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 Diazepam

Diazepam 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 this pairing. Your body turns adrafinil into modafinil, and modafinil can put the brakes on a liver enzyme called CYP2C19. That same enzyme helps clear diazepam (Valium) out of your system. If it slows down, diazepam can build up a bit more than usual.

What that might feel like is more of diazepam's normal effects: extra drowsiness, dizziness, foggy thinking, or feeling unsteady on your feet. The good news is this is a theoretical concern, based mostly on lab studies, not strong real-world data, so it's a maybe rather than a sure thing. Still, since both can affect alertness in opposite ways, it's worth a quick chat with your pharmacist or doctor 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

Diazepam 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 gist for diazepam (Valium) paired with adrafinil. Once your liver converts adrafinil into modafinil, that modafinil may gently nudge a liver enzyme called CYP1A2 to work a little faster. Since diazepam is partly handled by that enzyme, the theory is that your body could clear it slightly quicker, which might make it feel a bit weaker than usual.

In real life, this is a theoretical concern built on lab data, not strong human studies, so I wouldn't lose sleep over it. Still, if you lean on diazepam for anxiety, muscle spasms, or seizures, watch for those symptoms creeping back. Adrafinil also stresses the liver and is unregulated, so please loop in 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 2C9 (CYP2C9) SUBSTRATES

3 of 4

Diazepam 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: adrafinil turns into modafinil in your body, and modafinil may slow down a liver enzyme called CYP2C9, which is one of the routes your body uses to clear diazepam (Valium). If that enzyme works more slowly, diazepam could linger and build up a bit, leaving you with stronger effects than usual.

In real terms, that might mean extra drowsiness, grogginess, dizziness, or feeling unsteady on your feet. The good news is this concern is theoretical, drawn mostly from lab work, not from people, so it may not amount to much. Still, it's worth a quick chat with your pharmacist or doctor before combining them, especially since adrafinil itself is unregulated and can stress the liver. Don't change anything 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. 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

Diazepam 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 basic idea: your liver uses an enzyme called CYP3A4 to break down diazepam (Valium). When you take adrafinil, your body turns it into modafinil, and modafinil can gently speed up that enzyme. In theory, that means your body could clear diazepam a little faster than usual, which might leave you with less of the calming, anti-anxiety, or muscle-relaxing effect you're counting on.

I want to keep this in perspective, though. This is a theoretical concern based on how these drugs work, not something proven in studies, and modafinil is only a weak inducer. Still, if you rely on diazepam for seizures, spasms, or anxiety, a small drop in effect could matter. 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. 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 Diazepam 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.

From our Q&A

Questions About Adrafinil or Diazepam

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Adrafinil or Diazepam, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Diazepam

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Diazepam page lists 244 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 · 191 moderate · 44 minor.

Open the Diazepam 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 Diazepam 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 Diazepam 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

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

29 days ago today
Medication Diazepam
Top 5%

#99 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 Diazepam

What Is Diazepam Used For?

Brand names: Valium, Valium injection, Diastat AcuDial, Valtoco

  • Diazepam is used to relieve anxiety and to control agitation caused by alcohol withdrawal. It is also used along with other medications to control muscle spasms and spasticity caused by certain neurological disorders such as cerebral palsy (condition that causes difficulty with movement and balance), paraplegia (inability to move parts of the body), athetosis (abnormal muscle contractions), and stiff-man syndrome (a rare disorder with muscle rigidity and stiffness). Diazepam is also used along with other medications to control seizures. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain.

See full Diazepam 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 Diazepam Together: Common Questions

Can you take Adrafinil with Diazepam?
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 Diazepam?
Diazepam 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 Diazepam 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 Diazepam 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.