Drug & supplement interaction

Zizyphus + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

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

Acetaminophen, Butalbital, Codeine Phosphate falls into 2 drug categories that Zizyphus can interact with; the most serious is rated moderate. Theoretically, zizyphus might cause additive sedative effects when taken with CNS depressants.

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

Zizyphus and Acetaminophen, Butalbital, Codeine Phosphate

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

Why Are There 2 Interactions?

Zizyphus interacts with whole categories of medication. Acetaminophen, Butalbital, Codeine Phosphate falls into 2 of those categories, so it can interact with Zizyphus 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, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate falls under CNS DEPRESSANTS — the group Zizyphus interacts with.

Theoretically, zizyphus might cause additive sedative effects when taken with CNS depressants.
Some animal research has found that various parts of zizyphus have sedative effects. However, other animal research shows that zizyphus plant extract does not alter sleep parameters when used in combination with pentobarbital.
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

Your medication is a combination product, and two of its ingredients already slow down your nervous system. Butalbital is a barbiturate sedative, and codeine is an opioid pain reliever. Both can make you drowsy, foggy, lightheaded, or slow your breathing, especially at higher doses or when you first start them.

Zizyphus (jujube) has traditionally been used as a calming, sleep-promoting remedy, so the concern here is simply additive sleepiness, meaning the two together could leave you more tired or less alert than either alone. I want to be honest though: this is a theoretical caution based mostly on animal studies, and some of that research didn't even show an effect. Everyday culinary amounts of the fruit are unlikely to matter much. Still, if you take a concentrated supplement, run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Adzu, B., Amos, S., Dzarma, S., Wambebe, C., and Gamaniel, K. Effect of Zizyphus spina-christi Willd aqueous extract on the central nervous system in mice. J Ethnopharmacol. 2002;79(1):13-16.
  2. Morishita, S., Mishima, Y., Hirai, Y., Saito, T., and Shoji, M. Pharmacological studies of water extract of the Zizyphus seed and the Zizyphus seed containing drug. Gen Pharmacol 1987;18(6):637-641. PubMed
  3. Watanabe, I., Saito, H., and Takagi, K. Pharmacological studies of Zizyphus seeds. Jpn J Pharmacol 1973;23(4):563-571. DOI
  4. Wu, S. X., Zhang, J. X., Xu, T., Li, L. F., Zhao, S. Y., and Lan, M. Y. [Effects of seeds, leaves and fruits of Ziziphus spinosa and jujuboside A on central nervous system function]. Zhongguo Zhong Yao Za Zhi 1993;18(11):685-4.
  5. Hajhashemi V, Safaei A. Hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis extracts in mice. Res Pharm Sci. 2015 Nov-Dec;10(6):477-84.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 2

Acetaminophen, Butalbital, Codeine Phosphate also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, zizyphus might decrease the levels and clinical effects of drugs metabolized by CYP1A2.
Animal research shows that zizyphus induces CYP1A2 enzymes. However, 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 combo pill (Phrenilin with Codeine, which contains acetaminophen, butalbital, and codeine). The interaction on file is based only on animal studies, where zizyphus sped up a liver enzyme called CYP1A2. That theoretically could lower the levels of drugs cleared by that enzyme. So far, this has not been seen in people, so I'd file it under "possible but unproven."

For your specific medicine, CYP1A2 isn't the main pathway. Codeine is actually a prodrug that needs CYP2D6 to become active, and butalbital and acetaminophen clear through other routes. So I wouldn't expect a big real-world change. Still, since this is a sedating, habit-forming medicine, please run it by your pharmacist or doctor before adding zizyphus.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Jing XY, Peng YR, Wang XM, Duan JA. Effects of Ziziphus jujuba fruit extracts on cytochrome P450 (CYP1A2) activity in rats. Chin J Nat Med. 2015 Aug;13(8):588-94. 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

Zizyphus Also Interacts With Other Medications

Zizyphus has 468 moderate known drug interactions in our database — the Acetaminophen, Butalbital, Codeine Phosphate one above is among them. If you take anything else, check it against the full list below.

Moderate 468 No known interaction 2,362 (incl. Acetaminophen, Butalbital, Codeine Phosphate)
Taking anything else?

Check Another of Your Medications Against Zizyphus

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

Everything else you take

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

This page covers Zizyphus only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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 Gamma-hydroxybutyrate (ghb) (major).

Open the Acetaminophen, Butalbital, Codeine Phosphate interaction page

How much people look this up

Where Zizyphus and Acetaminophen, Butalbital, Codeine Phosphate 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 Zizyphus
Steady interest

#1,282 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,679 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 Zizyphus

What is Zizyphus?

Zizyphus
  • Sleep problems and insomnia
  • Anxiety and stress
  • Digestive support
  • General nutrition (vitamin C and fiber)
  • Constipation

Zizyphus (jujube) is an edible fruit and traditional remedy used mainly for sleep, anxiety, and digestion. The fruit is a nutritious food, but human evidence for its medicinal benefits is limited and mostly preliminary. If you want to try a supplement form, talk with your pharmacist or doctor first, especially if you are pregnant, breastfeeding, or taking other medicines.

Read the full Zizyphus monograph & all interactions
Keep checking

Other Drugs & Zizyphus

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

0Major
468Moderate
0Minor
2,361No known interaction
468 Moderate 2,361 No interaction
Moderate

468 interactions

Showing 60 of 468 moderate interactions — see all 468 on the Zizyphus page.

No interaction 2,361 drugs checked — show the list

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

Showing the 60 most looked-up of 2,361 medications checked with no known interaction — see the full Zizyphus list.

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

Can you take Zizyphus with Acetaminophen, Butalbital, Codeine Phosphate?
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 Zizyphus and Acetaminophen, Butalbital, Codeine Phosphate?
Acetaminophen, Butalbital, Codeine Phosphate belongs to more than one drug category, and Zizyphus 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 Zizyphus and Acetaminophen, Butalbital, Codeine Phosphate 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.