Drug & supplement interaction

Adrue + 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 Adrue can interact with; the most serious is rated moderate. Animal research suggests that taking adrue in combination with sodium thiopental or diazepam increases total sleep time up to four-fold compared to the effects of the drugs alone.

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

Adrue and Acetaminophen, Butalbital, Caffeine, Codeine

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

Why Are There 2 Interactions?

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

Moderate

CNS DEPRESSANTS

1 of 2

Why this applies to Acetaminophen, Butalbital, Caffeine, Codeine

Acetaminophen, Butalbital, Caffeine, Codeine falls under CNS DEPRESSANTS — the group Adrue interacts with.

Animal research suggests that taking adrue in combination with sodium thiopental or diazepam increases total sleep time up to four-fold compared to the effects of the drugs alone. Theoretically, concomitant use of adrue with CNS depressants might cause additive sedation. Some CNS depressants include benzodiazepines, such as diazepam (Valium), alprazolam (Xanax), triazolam (Halcion), and estazolam (ProSom); barbiturates, such as mephobarbital (Mebaral), phenobarbital (Luminal Sodium), and pentobarbital sodium (Nembutal); zolpidem (Ambien); and others.
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

This combination pill already carries two ingredients that calm the brain: butalbital (a barbiturate) and codeine (an opioid). Adrue has been studied mostly in animals, where it seemed to deepen and lengthen the sleep caused by sedatives. So the concern here is simple stacking, not a change in how your liver processes the medicine. Adrue's calming effect could pile on top of the butalbital and codeine.

In real life that might mean more drowsiness, dizziness, foggy thinking, or slowed breathing. Keep in mind this is a theoretical worry based on lab and animal work, not proven in people. Still, since both parts push the same direction, it's worth running past your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rakotonirina, V. S., Bum, E. N., Rakotonirina, A., and Bopelet, M. Sedative properties of the decoction of the rhizome of Cyperus articulatus. Fitoterapia 2001;72(1):22-29. PubMed
Moderate

BARBITURATES

2 of 2

Acetaminophen, Butalbital, Caffeine, Codeine also falls under BARBITURATES.

Animal research suggests that taking adrue in combination with sodium thiopental increases total sleep time three-fold compared to the effects of sodium thiopental alone. Theoretically, concomitant use of adrue and barbiturates might increase the risk of drowsiness and motor reflex depression. Some barbiturates include amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), pentobarbital (Nembutal), phenobarbital (Luminal), secobarbital (Seconal), and others.
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

The medication you're asking about is a combination product, and the piece that matters here is the butalbital, which is a barbiturate (a sedating, calming drug). It already pushes the brain in a relaxed, drowsy direction, and the codeine in this formula does the same thing on its own.

The concern with adrue is that it may add to that sedation. This is only a theoretical worry based on animal research, where adrue tripled the sleep time caused by a barbiturate. In real terms for you, the realistic risk is feeling extra drowsy, foggy, dizzy, or slow to react if you take both. We don't have human data to say how strong this is, so it's a maybe, not a sure thing. Please run it by your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rakotonirina, V. S., Bum, E. N., Rakotonirina, A., and Bopelet, M. Sedative properties of the decoction of the rhizome of Cyperus articulatus. Fitoterapia 2001;72(1):22-29. 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

Adrue Also Interacts With Other Medications

Adrue has 255 moderate 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 255 No known interaction 2,575 (incl. Acetaminophen, Butalbital, Caffeine, Codeine)
Taking anything else?

Check Another of Your Medications Against Adrue

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

Everything else you take

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

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

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

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

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

#988 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 Adrue

What is Adrue?

Adrue
  • Nausea and vomiting
  • Digestive upset, gas, and diarrhea
  • Calming or sedative effect
  • Traditional use for fevers and infections

Adrue (Cyperus articulatus) is a sedge whose rhizome has long been used in traditional medicine for nausea and other stomach complaints, and as a mild calming agent. Solid human studies are lacking, so its real benefits and safe doses are not well established. Talk to a pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Adrue monograph & all interactions
Keep checking

Other Drugs & Adrue

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

0Major
255Moderate
0Minor
2,574No known interaction
255 Moderate 2,574 No interaction
Moderate

255 interactions

Showing 60 of 255 moderate interactions — see all 255 on the Adrue page.

No interaction 2,574 drugs checked — show the list

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

Showing the 60 most looked-up of 2,574 medications checked with no known interaction — see the full Adrue list.

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

Can you take Adrue 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 Adrue and Acetaminophen, Butalbital, Caffeine, Codeine?
Acetaminophen, Butalbital, Caffeine, Codeine belongs to more than one drug category, and Adrue 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 Adrue 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.