Drug & supplement interaction

Uva Ursi + 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

Acetaminophen, Butalbital, Caffeine, Codeine falls into 2 drug categories that Uva Ursi can interact with; the most serious is rated moderate. Theoretically, uva ursi may decrease the metabolism of CYP3A4 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Uva Ursi and Acetaminophen, Butalbital, Caffeine, Codeine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Uva Ursi interacts with whole categories of medication. Acetaminophen, Butalbital, Caffeine, Codeine falls into 2 of those categories, so it can interact with Uva Ursi in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Uva Ursi interacts with.

Theoretically, uva ursi may decrease the metabolism of CYP3A4 substrates.
In vitro, uva ursi appears to inhibit CYP3A4. 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 honest picture: this concern comes from lab dish studies only, where uva ursi appeared to slow down a liver enzyme called CYP3A4. That same effect has never actually been seen in real people, so I wouldn't lose sleep over it. Of the ingredients in your combo pill, butalbital is partly handled by that pathway, so in theory blocking it could let butalbital linger a bit longer and add to drowsiness, dizziness, or feeling foggy.

One small wrinkle worth knowing: codeine is a prodrug your body converts into morphine through a different enzyme (CYP2D6), so this particular interaction shouldn't change its pain relief much. Since uva ursi is only meant for short-term use anyway, just give your pharmacist a heads-up before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chauhan B, Yu C, Krantis A, et al. In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P-glycoprotein. Can J Physiol Pharmacol. 2007;85(11):1099-107.
Moderate

GLUCURONIDATED DRUGS

2 of 2

Acetaminophen, Butalbital, Caffeine, Codeine also falls under GLUCURONIDATED DRUGS.

Theoretically, uva ursi may increase levels of drugs metabolized by glucuronidation.
In vitro, uva ursi extract appears to strongly inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1). However, uva ursi extract does not appear to inhibit UGT1A1 in animal models. 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 honest picture with this combination pill (which contains acetaminophen, butalbital, caffeine, and codeine). In a lab dish, uva ursi blocked an enzyme called UGT1A1 that helps your body clear out certain drugs through a process called glucuronidation. Acetaminophen is partly handled this way, so in theory uva ursi could slow its breakdown and let levels creep up.

But here's the key part: this was only seen in test tubes, and it did not hold up in animal studies, and it has never been reported in actual people. So I wouldn't lose sleep over it. Just keep your acetaminophen within safe daily limits, since too much can stress the liver, and check with your pharmacist before adding uva ursi.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Park JB, Kim D, Min JS, et al. Identification and characterization of in vitro inhibitors against UDP-glucuronosyltransferase 1A1 in uva-ursi extracts and evaluation of in vivo uva-ursi-drug interactions. Food Chem Toxicol. 2018;120:651-661. 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

Uva Ursi Also Interacts With Other Medications

Uva Ursi has 739 moderate, 63 minor known drug interactions in our database — the Acetaminophen, Butalbital, Caffeine, Codeine one above is among them. If you take anything else, check it against the full list below.

Moderate 739 Minor 63 No known interaction 2,028 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Uva Ursi

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

Everything else you take

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

This page covers Uva Ursi 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 Uva Ursi as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,423 real supplement products containing Uva Ursi, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Uva Ursi. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Caffeine, Codeine too, on top of Uva Ursi — 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 Uva Ursi 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 Uva Ursi
Top 25%

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

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

#923 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 Uva Ursi

What is Uva Ursi?

Uva Ursi
  • Urinary tract infections
  • Urinary discomfort
  • Mild diuretic
  • Kidney stones
  • Skin conditions

Uva ursi is a traditional herb used mainly for urinary tract infections, and its leaves contain a compound called arbutin that may have antimicrobial effects in the urine. Evidence in people is limited, and because high doses or long-term use may be harmful to the liver and could be toxic, it should only be used short-term and with guidance from a healthcare professional. Avoid it during pregnancy and breastfeeding.

Read the full Uva Ursi monograph & all interactions
Keep checking

Other Drugs & Uva Ursi

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

0Major
739Moderate
63Minor
2,027No known interaction
739 Moderate 63 Minor 2,027 No interaction
Moderate

739 interactions

Showing 60 of 739 moderate interactions — see all 739 on the Uva Ursi page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Uva Ursi page.

No interaction 2,027 drugs checked — show the list

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

Showing the 60 most looked-up of 2,027 medications checked with no known interaction — see the full Uva Ursi list.

See the full Uva Ursi 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
Uva Ursi 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 Uva Ursi and Acetaminophen, Butalbital, Caffeine, Codeine Together: Common Questions

Can you take Uva Ursi 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.
Why are there 2 interactions listed for Uva Ursi and Acetaminophen, Butalbital, Caffeine, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine belongs to more than one drug category, and Uva Ursi 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 Uva Ursi 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

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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.