Drug & supplement interaction

Adrafinil + Fluconazole

Fluconazole brand names: Diflucan, Diflucan Injection.

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

Adrafinil has a moderate interaction with Fluconazole. 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?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Adrafinil and Fluconazole

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS

Why this applies to Fluconazole

Fluconazole 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 the situation if you're considering adrafinil while taking fluconazole (Diflucan). Fluconazole slows down a liver enzyme called CYP3A4, and that same enzyme helps break down modafinil, which is the active drug your body makes from adrafinil. So by blocking that pathway, fluconazole could let modafinil hang around longer and build up more than expected.

In real terms, that might mean stronger or longer-lasting stimulant effects: trouble sleeping, headache, a racing or pounding heart, jitteriness, nausea, or feeling anxious. I want to be honest though, this is a theoretical concern based on how the drugs work, not something proven in studies. Adrafinil is also unregulated and hard on the liver. Please check with your pharmacist or doctor 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, 1,057 moderate known drug interactions in our database — the Fluconazole one above is one of them. If you take anything else, check it against the full list below.

Major 1 Moderate 1,057 No known interaction 1,772 (incl. Fluconazole)
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 Fluconazole

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 Fluconazole, 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 Fluconazole

This page covers Adrafinil only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fluconazole page lists 81 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Siberian Cocklebur (major), Wine (major) and Ashwagandha (moderate).

By severity: 4 major · 54 moderate · 23 minor.

From our pharmacist’s overview on the Fluconazole page

“Fluconazole (Diflucan) treats fungal infections, and I would pair it with supplements carefully. Nearly half of the 81 ingredients with an interaction on file, 38 of them, put extra strain on the liver, which is already busy processing the antifungal.”

Reviewed by 2 · Jul 18, 2026

Open the Fluconazole 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 Fluconazole 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 Fluconazole 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

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

29 days ago today
Medication Fluconazole
Top half

#736 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 Fluconazole

What Is Fluconazole Used For?

Brand names: Diflucan, Diflucan Injection

Fluconazole treats several fungal infections. These include Candida infections of the mouth, throat and esophagus (the tube from the throat to the stomach), and cryptococcal meningitis (a fungal infection of the lining around the brain).

Vaginal yeast infections are a labeled use of the tablets (Diflucan and fluconazole tablets) and of products labeled for both tablets and suspension. They are not listed for fluconazole oral suspension on its own or for the intravenous (IV) products. All products are also used to lower the chance of candidiasis in people having chemotherapy and/or radiation before a bone marrow transplant.

See full Fluconazole 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
1 Major 1,057 Moderate 1,771 No 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.

See the full Adrafinil interactions page
See every supplement checked against Fluconazole, 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 Fluconazole supplement interactions › Every supplement checked against Fluconazole, ranked by severity Fluconazole 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 Fluconazole Together: Common Questions

Can you take Adrafinil with Fluconazole?
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 Fluconazole 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 Fluconazole and Adrafinil?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.