Drug & supplement interaction

Zizyphus + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

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

Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen

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. Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen 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

Here's the simple version: Apadaz (benzhydrocodone with acetaminophen) is a narcotic pain reliever, and one of its main effects is calming down the brain and nervous system. That's where drowsiness, slowed breathing, and that foggy, relaxed feeling come from. Zizyphus (jujube) has long been used as a calming, sleep-promoting remedy, so the worry is that stacking the two could deepen that sedation.

I want to be honest about the evidence here, though. This is a theoretical concern based mostly on animal studies, and even those results are mixed. Eating jujube fruit as a food is very unlikely to cause trouble. A concentrated supplement is more of a question mark. To be safe, watch for extra sleepiness or dizziness, and check with your pharmacist or doctor before combining them.

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

Benzhydrocodone, Acetaminophen 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 situation with Apadaz (benzhydrocodone plus acetaminophen). The benzhydrocodone part is actually a prodrug, meaning your body has to convert it into hydrocodone before it can ease your pain. Some lab and animal studies hint that Zizyphus may speed up a liver enzyme called CYP1A2. If that sped-up clearance applied to this medicine, in theory it could lower the active drug levels, so you might get less pain relief than expected.

The honest truth is this is very weak evidence. It has only been seen in animals, never confirmed in people, and the main pain pathway here is a different enzyme anyway. Eating jujube fruit as food almost certainly won't matter. Still, if you're using a concentrated supplement, just mention it to your pharmacist or doctor.

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 Benzhydrocodone, Acetaminophen 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. Benzhydrocodone, Acetaminophen)
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 Benzhydrocodone, Acetaminophen

This page covers Zizyphus only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Benzhydrocodone, Acetaminophen page lists 299 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).

By severity: 14 major · 239 moderate · 46 minor.

Open the Benzhydrocodone, Acetaminophen interaction page

How much people look this up

Where Zizyphus and Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen
Steady interest

#2,225 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
Medication

About Benzhydrocodone and Acetaminophen

What Is Benzhydrocodone and Acetaminophen Used For?

Brand name: Apadaz

Apadaz is indicated for the short-term management of acute pain — up to 14 days — that is severe enough to require an opioid and for which non-opioid treatments have not worked or are not expected to work. It combines benzhydrocodone (a prodrug that converts to the opioid hydrocodone) with acetaminophen.

Because of serious risks including addiction, abuse, and misuse, Apadaz is reserved for patients who have not tolerated or have not gotten adequate relief from alternative pain treatments. It should not be used for an extended period of time unless the pain remains severe enough to require an opioid and alternatives remain inadequate.

See full Benzhydrocodone and Acetaminophen drug information
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 Benzhydrocodone, Acetaminophen, 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 Benzhydrocodone, Acetaminophen supplement interactions › Every supplement checked against Benzhydrocodone, Acetaminophen, ranked by severity Benzhydrocodone and Acetaminophen 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 Zizyphus and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Zizyphus with Benzhydrocodone, Acetaminophen?
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 Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen 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 Benzhydrocodone, Acetaminophen 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.