Drug & supplement interaction

Schizonepeta + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

Moderate Interaction
The bottom line Moderate

Benzhydrocodone, Acetaminophen falls into 4 drug categories that Schizonepeta can interact with; the most serious is rated moderate. Animal research suggests that schizonepetin, a monoterpene constituent of schizonepeta, inhibits cytochrome P450 (CYP) 2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Schizonepeta and Benzhydrocodone, Acetaminophen

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Schizonepeta interacts with whole categories of medication. Benzhydrocodone, Acetaminophen falls into 4 of those categories, so it can interact with Schizonepeta in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 4

Why this applies to Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Schizonepeta interacts with.

Animal research suggests that schizonepetin, a monoterpene constituent of schizonepeta, inhibits cytochrome P450 (CYP) 2D6. Theoretically, schizonepeta might increase the effects and side effects of CYP2D6 substrates.
Some substrates of CYP2D6 include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), 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

Here's the thing about the benzhydrocodone in Apadaz: it's a prodrug. Once you swallow it, your body converts it to hydrocodone, and then an enzyme called CYP2D6 turns part of that into hydromorphone, which adds to the pain relief. Schizonepeta has been shown (in lab and animal studies only) to slow down that same CYP2D6 enzyme.

So in theory, blocking CYP2D6 could mean a bit less of the stronger pain-relieving form being made, which might mean weaker relief for some people. This is unproven and based on early research, not human studies, so I wouldn't lose sleep over it. Still, before pairing them, it's worth a quick chat with your pharmacist or doctor, especially since this is an opioid.

References
  1. Bao B, Geng T, Cao Y, et al. Effects of schizonepetin on activity of mRNA expression of cytochrome P450 enzymes in rats. Int J Mol Sci. 2012;13(12):17006-18.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 4

Benzhydrocodone, Acetaminophen also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Animal research suggests that schizonepetin, a monoterpene constituent of schizonepeta, inhibits cytochrome P450 (CYP) 1A2. Theoretically, schizonepeta might increase the effects and side effects of CYP1A2 substrates.
Some substrates of CYP1A2 include clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zileuton (Zyflo), zolmitriptan (Zomig), 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

Here's the honest picture. Schizonepeta has been shown, but only in animal and test-tube studies, to slow down a liver enzyme called CYP1A2. The worry is that if this enzyme is blocked, certain medications it normally clears could build up and hit you harder. With Apadaz (benzhydrocodone with acetaminophen), the main concern would be more opioid effects, like extra drowsiness, dizziness, slowed breathing, constipation, or feeling foggy.

That said, benzhydrocodone is mostly activated and broken down by other pathways, so CYP1A2 isn't its main route. This interaction is theoretical and the evidence is weak. Still, since opioids carry real risks, I'd run any Schizonepeta use past your pharmacist or doctor before combining them. Please don't change your medicine on your own.

References
  1. Bao B, Geng T, Cao Y, et al. Effects of schizonepetin on activity of mRNA expression of cytochrome P450 enzymes in rats. Int J Mol Sci. 2012;13(12):17006-18.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

Benzhydrocodone, Acetaminophen also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Animal research suggests that schizonepetin, a monoterpene constituent of schizonepeta, induces cytochrome P450 (CYP) 3A4. Theoretically, schizonepeta might decrease the effects of CYP3A4 substrates.
Some substrates of CYP3A4 include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), and numerous 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

Here's something worth knowing about Apadaz (benzhydrocodone with acetaminophen). The benzhydrocodone part is actually a prodrug, meaning your body has to convert it into active hydrocodone before it relieves pain. Schizonepeta, based only on animal and lab studies, may speed up the CYP3A4 enzyme that handles drugs like this. In theory, a faster enzyme could shift how much active drug you get and how long it sticks around, which might make your pain control feel less steady or less reliable.

I want to be honest: this is very weak, theoretical evidence, so I wouldn't lose sleep over it. Still, with an opioid involved, even small changes matter. If you're taking Apadaz for real pain, just check with your pharmacist or doctor before adding Schizonepeta.

References
  1. Bao B, Geng T, Cao Y, et al. Effects of schizonepetin on activity of mRNA expression of cytochrome P450 enzymes in rats. Int J Mol Sci. 2012;13(12):17006-18.
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

4 of 4

Benzhydrocodone, Acetaminophen also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Animal research suggests that schizonepetin, a monoterpene constituent of schizonepeta, inhibits cytochrome P450 (CYP) 2E1. Theoretically, schizonepeta might increase the effects and side effects of CYP2E1 substrates.
Some substrates of CYP2E1 include acetaminophen, chlorzoxazone (Parafon Forte), ethanol, theophylline, and anesthetics such as enflurane (Ethrane), halothane (Fluothane), isoflurane (Forane), and methoxyflurane (Penthrane).
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 piece that matters in Apadaz: the acetaminophen part. Your liver uses an enzyme called CYP2E1 to handle some of that acetaminophen. In lab and animal studies, a compound in Schizonepeta seemed to slow that enzyme down. In theory, if acetaminophen clears a little slower, more could linger in your system. I want to be honest, though, this is only test-tube and animal data, so we really don't know if it does anything in real people.

The bigger acetaminophen worry is always your liver, especially if you take a lot, drink alcohol, or use other products with acetaminophen in them. The opioid side (benzhydrocodone) isn't the focus here. Before mixing them, just run it by your pharmacist or doctor so they can check your total daily acetaminophen.

References
  1. Bao B, Geng T, Cao Y, et al. Effects of schizonepetin on activity of mRNA expression of cytochrome P450 enzymes in rats. Int J Mol Sci. 2012;13(12):17006-18.

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

Schizonepeta Also Interacts With Other Medications

Schizonepeta has 796 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.

Taking anything else?

Check Another of Your Medications Against Schizonepeta

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

Everything else you take

See Every Supplement That Interacts With Benzhydrocodone, Acetaminophen

This page covers Schizonepeta 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

One more smart check

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

We hold 285 real supplement products containing Schizonepeta, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Schizonepeta. Your product may carry other ingredients that interact with Benzhydrocodone, Acetaminophen too, on top of Schizonepeta — 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 Schizonepeta 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 Schizonepeta
Top half

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,159 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 Schizonepeta

What is Schizonepeta?

  • Common cold and early-stage fever
  • Itchy skin rashes and hives
  • Sore throat
  • Headache
  • Measles and other skin eruptions (traditional use)

Schizonepeta is a mint-family herb long used in traditional Chinese medicine, usually as part of combination formulas for colds, fevers, and itchy skin conditions. Modern human evidence is very limited, so its benefits are not well proven. Talk to a pharmacist or doctor before using it, especially if you are pregnant, breastfeeding, or taking other medicines.

Read the full Schizonepeta 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 & Schizonepeta

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

0Major
796Moderate
0Minor
2,033No known interaction
Moderate

796 interactions

Showing 60 of 796 moderate interactions — see all 796 on the Schizonepeta page.

No interaction 2,033 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Schizonepeta and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Schizonepeta 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 4 interactions listed for Schizonepeta and Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen belongs to more than one drug category, and Schizonepeta 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 Schizonepeta 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.