Drug & supplement interaction

Bilberry + Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine brand names: Esgic with Codeine, Fioricet w/ Codeine.

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

Bilberry has a moderate interaction with Acetaminophen, Butalbital, Caffeine, Codeine. Theoretically, bilberry fruit extract might decrease levels of drugs metabolized by CYP2E1.

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

Bilberry and Acetaminophen, Butalbital, Caffeine, Codeine

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

Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES — the group Bilberry interacts with.

Theoretically, bilberry fruit extract might decrease levels of drugs metabolized by CYP2E1.
Animal research shows that exposure to small concentrations of bilberry extract in drinking water for around one month increased CYP2E1 activity by 31%. However, exposure over a 2-month period did not increase CYP2E1 activity. This effect has not been reported in humans.
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 short version: this is a very weak, theory-only concern, so I wouldn't lose sleep over it. The idea is that bilberry might slightly speed up an enzyme called CYP2E1, which is one of the pathways that handles the acetaminophen part of this combo pill. If that enzyme runs faster, more acetaminophen could be shunted into a harmful byproduct that stresses the liver, especially with regular use or higher doses.

But honestly, this comes only from animal studies, and even there the effect faded after two months. It has never been shown in people. The butalbital, caffeine, and codeine pieces aren't really part of this. Eating bilberries is no worry at all. If you take concentrated bilberry supplements daily, just mention it to your pharmacist so they can keep an eye on your acetaminophen total.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Prokop J, Lněničková K, Cibicek N, et al. Effect of bilberry extract (Vaccinium myrtillus L.) on drug-metabolizing enzymes in rats. Food Chem Toxicol 2019;129:382-90. PubMed

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

Bilberry Also Interacts With Other Medications

Bilberry has 274 moderate known drug interactions in our database — the Acetaminophen, Butalbital, Caffeine, Codeine one above is one of them. If you take anything else, check it against the full list below.

Moderate 274 No known interaction 2,556 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Bilberry

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Butalbital, Caffeine, Codeine

This page covers Bilberry only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Caffeine, Codeine page lists 305 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), Asarabacca (major), Beer (major) and Ephedra (major).

By severity: 15 major · 245 moderate · 45 minor.

Open the Acetaminophen, Butalbital, Caffeine, Codeine interaction page

One more smart check

Taking Bilberry as Part of a Dietary Supplement Product? Check It for Interactions

We hold 3,883 real supplement products containing Bilberry, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bilberry. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine, Codeine too, on top of Bilberry — 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 Bilberry and Acetaminophen, Butalbital, Caffeine, Codeine 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 Bilberry
Top 10%

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

29 days ago today
Medication Acetaminophen, Butalbital, Caffeine, Codeine
Top half

#911 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 Bilberry

What is Bilberry?

Bilberry
  • Eye and vision health
  • Antioxidant support
  • Diarrhea and digestive upset
  • Circulation and vein health
  • Blood sugar support

Bilberry is a blueberry-like fruit rich in antioxidant plant compounds called anthocyanins, and it has a long history of traditional use for eye health, circulation, and mild diarrhea. While it is generally well tolerated as a food and supplement, strong scientific proof for most health claims is limited. Talk with your pharmacist or doctor before using bilberry supplements, especially if you are pregnant, breastfeeding, or have a health condition.

Read the full Bilberry monograph & all interactions
Keep checking

Other Drugs & Bilberry

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

0Major
274Moderate
0Minor
2,555No known interaction
274 Moderate 2,555 No interaction
Moderate

274 interactions

Showing 60 of 274 moderate interactions — see all 274 on the Bilberry page.

No interaction 2,555 drugs checked — show the list

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

Showing the 60 most looked-up of 2,555 medications checked with no known interaction — see the full Bilberry list.

See the full Bilberry interactions page
See every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, 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
Bilberry monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Caffeine, Codeine supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Caffeine, Codeine, ranked by severity 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 Bilberry and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Bilberry with Acetaminophen, Butalbital, Caffeine, Codeine?
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 Bilberry and Acetaminophen, Butalbital, Caffeine, Codeine 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 Acetaminophen, Butalbital, Caffeine, Codeine and Bilberry?

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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.