Drug & supplement interaction

Sweet Annie + 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 Sweet Annie can interact with; the most serious is rated moderate. Theoretically, concomitant use might have additive adverse hepatotoxic effects.

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

Sweet Annie and Benzhydrocodone, Acetaminophen

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

Why Are There 2 Interactions?

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

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen falls under HEPATOTOXIC DRUGS — the group Sweet Annie interacts with.

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
There is some concern that Sweet Annie can adversely affect the liver.
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 to keep in mind with Apadaz: it contains acetaminophen, the same ingredient in Tylenol, which the liver has to process. In large or long-term amounts, acetaminophen is one of the more common causes of liver strain. Sweet Annie (Artemisia annua) has its own reports of being hard on the liver in some people.

So the worry here is mostly additive: two things that may each tax your liver at the same time. The evidence for the Sweet Annie part is mostly anecdotal, so this is more theoretical than proven. Still, watch for signs like yellowing skin or eyes, dark urine, belly pain, or unusual tiredness. Before pairing them, check with your pharmacist or doctor, and never exceed the acetaminophen dose on the label.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Centers for Disease Control and Prevention (CDC). Hepatitis temporally associated with an herbal supplement containing artemisinin-Washington, 2008. MMWR Morb Mortal Wkly Rep 2009;58:854-8.
  2. Savage RL, Hill GR, Barnes J, Kenyon SH, Tatley MV. Suspected hepatotoxicity with a supercritical carbon dioxide extract of Artemisia annua in grapeseed oil used in New Zealand. Front Pharmacol. 2019;10:1448. PubMed
  3. Ruperti-Repilado FJ, Haefliger S, Rehm S, et al. Danger of herbal tea: a case of acute cholestatic hepatitis due to Artemisia annua tea. Front Med (Lausanne). 2019;6:221. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Sweet Annie may alter plasma levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that the Sweet Annie constituent artemisinin induces CYP3A4, possibly increasing CYP3A4 activity by 1.9-fold. However, Sweet Annie extract seems to inhibit the activity of CYP3A4 in vitro, suggesting that other constituents of Sweet Annie play a role in its effects on the overall activity of this enzyme. More information is needed to determine whether taking Sweet Annie extract affects the metabolism of CYP3A4 substrates.
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 hydrocodone before it can ease your pain, and enzymes like CYP3A4 are involved in handling it. Sweet Annie's main compound, artemisinin, has been shown in lab studies to possibly speed up CYP3A4, which could shift how much active drug you end up with.

The honest truth is the evidence here is weak. It comes only from test tube studies, and even those are mixed, with parts of the plant pushing the enzyme one way and other parts the opposite. So I wouldn't lose sleep over it, but since this is an opioid where too little means poor pain control and too much can mean heavy sedation or slowed breathing, 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. Xing J, Kirby BJ, Whittington D, et al. Evaluation of P450 inhibition and induction by artemisinin antimalarials in human liver microsomes and primary human hepatocytes. Drug Metabl Dispos 2012;40(9):1757-64. PubMed
  2. Kane NF, Kiani BH, Desrosiers MR, Towler MJ, Weathers PJ. Artemisia extracts differ from artemisinin effects on human hepatic CYP450s 2B6 and 3A4 in vitro. J Ethnopharmacol 2022. DOI

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

Sweet Annie Also Interacts With Other Medications

Sweet Annie has 888 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 888 No known interaction 1,942 (incl. Benzhydrocodone, Acetaminophen)
Taking anything else?

Check Another of Your Medications Against Sweet Annie

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

Everything else you take

See Every Supplement That Interacts With Benzhydrocodone, Acetaminophen

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

We hold 243 real supplement products containing Sweet Annie, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sweet Annie. Your product may carry other ingredients that interact with Benzhydrocodone, Acetaminophen too, on top of Sweet Annie — 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 Sweet Annie 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 Sweet Annie
Steady interest

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,118 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 Sweet Annie

What is Sweet Annie?

Sweet Annie
  • Malaria (traditional)
  • Fever
  • Inflammation
  • Digestive complaints
  • Antimicrobial support
  • Insect repellent

Sweet Annie (Artemisia annua) is the source of artemisinin, a compound used in prescription antimalarial drugs. While the purified drug is well studied for malaria, the herb itself as a supplement is not proven for the wide range of conditions people use it for, and self-treating malaria with the raw herb is dangerous. Talk to a pharmacist or doctor before using it.

Read the full Sweet Annie 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 & Sweet Annie

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

0Major
888Moderate
0Minor
1,941No known interaction
888 Moderate 1,941 No interaction
Moderate

888 interactions

Showing 60 of 888 moderate interactions — see all 888 on the Sweet Annie page.

No interaction 1,941 drugs checked — show the list

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

Showing the 60 most looked-up of 1,941 medications checked with no known interaction — see the full Sweet Annie list.

See the full Sweet Annie 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
Sweet Annie 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 Sweet Annie and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Sweet Annie 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 Sweet Annie and Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen belongs to more than one drug category, and Sweet Annie 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 Sweet Annie 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

Still Have a Question About Benzhydrocodone, Acetaminophen and Sweet Annie?

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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.