Drug & supplement interaction

Caffeine + Fluconazole

Fluconazole brand names: Diflucan, Diflucan Injection.

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

Caffeine has a minor interaction with Fluconazole. Theoretically, fluconazole might increase the levels and adverse effects of caffeine.

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

Caffeine and Fluconazole

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

Minor

FLUCONAZOLE (Diflucan)

Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Fluconazole decreases caffeine clearance by approximately 25%.
Severity Minor Likelihood Possible Evidence B

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 this pair: fluconazole can slow down how fast your body clears caffeine, by roughly a quarter. The caffeine isn't doing anything to the fluconazole, so your infection treatment keeps working fine. The flip side is that the caffeine you drink may linger a bit longer and hit a little harder than usual.

In practice that might mean feeling more wired, a faster or pounding heartbeat, jitters, or trouble sleeping, especially if you're already a big coffee or energy drink fan. This is rated minor and is mostly theoretical, so most people do fine. If you notice those buzzy effects while on fluconazole, just ease back on the caffeine and mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nix D, Zelenitsky S, Symonds W, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly subjects. Clin Pharmacol Ther 1992;51:183. DOI

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

Caffeine Also Interacts With Other Medications

Caffeine has 8 major, 483 moderate, 163 minor 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 8 Moderate 483 Minor 163 No known interaction 2,176 (incl. Fluconazole)
Taking anything else?

Check Another of Your Medications Against Caffeine

Covers the 2,830 medications we’ve checked against Caffeine. Pick one to open its full report.

From our Q&A

Questions About Caffeine 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 Caffeine 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 Caffeine 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 Adrafinil (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 Caffeine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 6,775 real supplement products containing Caffeine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Caffeine. Your product may carry other ingredients that interact with Fluconazole too, on top of Caffeine — 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 Caffeine 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 Caffeine
Top 5%

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

29 days ago today
Medication Fluconazole
Top half

#906 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 Caffeine

What is Caffeine?

  • Mental alertness and reducing fatigue
  • Improving athletic performance
  • Headache and migraine relief
  • Boosting focus and concentration
  • Weight loss aid

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too much can cause jitteriness, a racing heart, and sleep problems. Pregnant women and people with heart conditions or anxiety should be especially careful and check with a doctor or pharmacist.

Read the full Caffeine monograph & all interactions
Medication

About Fluconazole

What Is Fluconazole Used For?

Brand names: Diflucan, Diflucan Injection

Fluconazole treats infections caused by Candida and Cryptococcus fungi. Diflucan tablets and oral suspension, fluconazole tablets, and fluconazole oral suspension and tablets are approved for vaginal yeast infections (vaginal candidiasis), mouth and throat yeast infections (oropharyngeal candidiasis), and esophageal candidiasis. All formulations, including the intravenous injection, are used for cryptococcal meningitis (a fungal infection of the brain lining). In smaller studies, fluconazole was also effective for Candida urinary tract infections, peritonitis (abdominal lining infection), and serious systemic infections such as candidemia (Candida in the bloodstream) and disseminated candidiasis.

Fluconazole is also used as preventive therapy: Diflucan, fluconazole tablets, fluconazole oral suspension, and fluconazole injection are all indicated to reduce the risk of candidiasis in patients undergoing bone marrow transplantation who receive chemotherapy and/or radiation therapy. Note that the oral suspension formulations are not approved for vaginal candidiasis — that indication applies only to Diflucan tablets/suspension and fluconazole tablets/tablet-suspension products.

See full Fluconazole drug information
Keep checking

Other Drugs & Caffeine

Browse every other medication we’ve checked against Caffeine — both the ones with a known interaction and the ones without. Select any drug for the full detail.

8Major
483Moderate
163Minor
2,175No known interaction
8 Major 483 Moderate 163 Minor 2,175 No interaction
Major

8 interactions

Moderate

483 interactions

Showing 60 of 483 moderate interactions — see all 483 on the Caffeine page.

Minor

163 interactions

Showing 60 of 163 minor interactions — see all 163 on the Caffeine page.

No interaction 2,175 drugs checked — show the list

We also checked Caffeine against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,175 medications checked with no known interaction — see the full Caffeine list.

See the full Caffeine 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
Caffeine 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 Caffeine and Fluconazole Together: Common Questions

Can you take Caffeine with Fluconazole?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Caffeine and Fluconazole interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Fluconazole and Caffeine?

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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.