Drug & supplement interaction

Fo-ti + Benzhydrocodone, Acetaminophen

Benzhydrocodone, Acetaminophen brand name: Apadaz.

Moderate Interaction
The bottom line Moderate

Benzhydrocodone, Acetaminophen falls into 4 drug categories that Fo-ti can interact with; the most serious is rated moderate. Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2D6.

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

Fo-ti and Benzhydrocodone, Acetaminophen

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

Why Are There 4 Interactions?

Fo-ti interacts with whole categories of medication. Benzhydrocodone, Acetaminophen falls into 4 of those categories, so it can interact with Fo-ti 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 Fo-ti interacts with.

Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2D6.
Animal research suggests that fo-ti might inhibit CYP2D6. Additionally, an in vitro study suggests that the degree of CYP2D6 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, this interaction 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 wrinkle with Apadaz: the benzhydrocodone part is a prodrug. Your body has to convert it (with help from an enzyme called CYP2D6) into hydrocodone, the piece that actually relieves pain. So this isn't a case where a blocker makes the drug pile up. If Fo-ti slows CYP2D6, you may actually get less active pain relief from your dose.

Honestly, though, this is mostly theory. The signal comes from lab and animal studies, and raw Fo-ti seemed to block the enzyme more than processed extracts. It has not been shown in real people. Since Fo-ti also carries its own liver concerns, please run it by your pharmacist or doctor before pairing it with Apadaz.

References
  1. Zhang Y, Ding T, Diao T, Deng M, Chen S. Effects of Polygonum multiflorum on the activity of cytochrome P450 isoforms in rats. Pharmazie 2015;70(1):47-54. DOI
  2. Xing Y, Yu Q, Zhou L, et al. Cytochrome P450-mediated herb-drug interaction (HDI) of Polygonum multiflorum Thunb. based on pharmacokinetic studies and in vitro inhibition assays. Phytomedicine 2023;112:154710. PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

2 of 4

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

Theoretically, fo-ti might increase or decrease the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that fo-ti might inhibit CYP1A2. Additionally, in vitro research suggests that the degree of CYP1A2 inhibition depends on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, in an animal study, an aqueous extract of fo-ti inhibited CYP1A2 while an alcoholic extract of fo-ti induced CYP1A2. Induction or inhibition of CYP1A2 by fo-ti 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 for Apadaz (benzhydrocodone with acetaminophen). The interaction on file involves the liver enzyme CYP1A2, and Fo-ti has only shown effects on that enzyme in test-tube and animal studies. Nothing like this has been confirmed in real people, so I'd file this under theoretical rather than something to lose sleep over.

One thing worth knowing: benzhydrocodone is a prodrug, meaning your body has to convert it into its active painkiller (hydrocodone). That activation leans mostly on a different enzyme (CYP2D6), not CYP1A2, so the CYP1A2 concern here is pretty indirect. If Fo-ti did shift enzyme activity, you could in theory see slightly stronger or weaker pain relief, or more drowsiness and constipation. Because Fo-ti has also been tied to liver injury, and acetaminophen is hard on the liver too, please run this combo by your pharmacist or doctor first.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Zhang Y, Ding T, Diao T, Deng M, Chen S. Effects of Polygonum multiflorum on the activity of cytochrome P450 isoforms in rats. Pharmazie 2015;70(1):47-54. DOI
  3. Xing Y, Yu Q, Zhou L, et al. Cytochrome P450-mediated herb-drug interaction (HDI) of Polygonum multiflorum Thunb. based on pharmacokinetic studies and in vitro inhibition assays. Phytomedicine 2023;112:154710. PubMed
Moderate

HEPATOTOXIC DRUGS

3 of 4

Benzhydrocodone, Acetaminophen also falls under HEPATOTOXIC DRUGS.

Theoretically, fo-ti might increase the risk of liver damage when taken with hepatotoxic drugs.
Fo-ti has been linked to liver damage in many reports.
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 main thing to keep in mind: the concern with combining Fo-ti and Apadaz isn't about how the medicine works in your brain or how strong your pain relief is. It's about your liver. The acetaminophen half of Apadaz is processed by the liver, and Fo-ti (especially the processed root) has been linked in real-world reports to liver injury. Stacking the two could add stress on that same organ.

To be fair, this is based on scattered case reports, not solid studies, so it's more of a 'be cautious' flag than a proven danger. Still, watch for yellowing of the skin or eyes, dark urine, belly pain, or unusual tiredness. Please check with your pharmacist or doctor before pairing these, and never take more acetaminophen than directed.

References
  1. Park GJ, Mann SP, Ngu MC. Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum. J Gastroenterol Hepatol 2001;16:115-7.
  2. But PP, Tomlinson B, Lee KL. Hepatitis related to the Chinese medicine Shou-wu-pian manufactured from Polygonum multiflorum. Vet Hum Toxicol 1996;38:280-2.
  3. UK Medicines and Healthcare Products Regulatory Agency. Polygonum multiflorum and liver reactions. April 2006. Available at: www.mhra.gov.uk/home/idcplg?IdcService= SS_GET_PAGE&useSecondary=true&ssDocName= CON2023590&ssTargetNodeId= 833 (Accessed 10 May 2
  4. Panis B, Wong DR, Hooymans PM, De Smet PA, Rosias PP. Recurrent toxic hepatitis in a Caucasian girl related to the use of Shou-Wu-Pian, a Chinese herbal preparation. J Pediatr Gastroenterol Nutr 2005;41:256-8. PubMed
  5. Mazzanti G, Battinelli L, Daniele C, et al. New case of acute hepatitis following the consumption of Shou Wu Pian, a Chinese herbal product derived from Polygonum multiflorum. Ann Intern Med 2004;140:E589-90.
  6. Cardenas A, Restrepo JC, Sierra F, Correa G. Acute hepatitis due to shen-min: a herbal product derived from Polygonum multiflorum. J Clin Gastroenterol 2006;40:629-32. PubMed
  7. Laird AR, Ramchandani N, deGoma EM, et al. Acute hepatitis associated with the use of an herbal supplement (Polygonum multiflorum) mimicking iron-overload syndrome. J Clin Gastroenterol 2008;42:861-2. PubMed
  8. Jung KA, Min HJ, Yoo SS, et al. Drug-Induced Liver Injury: Twenty Five Cases of Acute Hepatitis Following Ingestion of Polygonum multiflorum Thunb. Gut Liver 2011;5(4):493-9. PubMed
  9. Yuen, M. F., Tam, S., Fung, J., Wong, D. K., Wong, B. C., and Lai, C. L. Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study. Aliment.Pharmacol.Ther 10-15-2006;24(8):1179-1186. PubMed
  10. Bae, S. H., Kim, D. H., Bae, Y. S., Lee, K. J., Kim, D. W., Yoon, J. B., Hong, J. H., and Kim, S. H. [Toxic hepatitis associated with Polygoni multiflori]. Korean J.Hepatol. 2010;16(2):182-186. PubMed
  11. Furukawa, M., Kasajima, S., Nakamura, Y., Shouzushima, M., Nagatani, N., Takinishi, A., Taguchi, A., Fujita, M., Niimi, A., Misaka, R., and Nagahara, H. Toxic hepatitis induced by show-wu-pian, a Chinese herbal preparation. Intern.Med. 2010;49(15):1537-1 PubMed
  12. Dong H, Slain D, Cheng J, Ma W, Liang W. Eighteen cases of liver injury following ingestion of Polygonum multiflorum. Complement Ther Med 2014;22(1):70-4. PubMed
  13. Lei X, Chen J, Ren J, et al. Liver damage associated with Polygonum multiflorum Thunb.: a systematic review of case reports and case series. Evid Based Complement Alternat Med 2015;2015:459749.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 4

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

Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research suggests that fo-ti might inhibit CYP3A4. One in vitro study suggests that the degree of CYP3A4 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, this evidence conflicts with animal research suggesting that fo-ti does not inhibit CYP3A4. This interaction 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 thing about Apadaz: the benzhydrocodone part is actually a prodrug, meaning your body has to convert it into hydrocodone (and then partly into morphine) before it relieves pain. Some of this opioid is handled by an enzyme called CYP3A4. In lab dishes, Fo-ti has shown it might slow CYP3A4 down. If that happened in a person, the opioid could linger longer and hit harder, which may mean more drowsiness, dizziness, constipation, nausea, or in a worst case, slowed breathing.

I want to be straight with you though: this is only test-tube research, animal studies disagreed, and it has never actually been reported in real patients. So I wouldn't panic. Still, opioids are nothing to gamble with, so please run this combo past your pharmacist or doctor first.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Zhang Y, Ding T, Diao T, Deng M, Chen S. Effects of Polygonum multiflorum on the activity of cytochrome P450 isoforms in rats. Pharmazie 2015;70(1):47-54. DOI
  3. Xing Y, Yu Q, Zhou L, et al. Cytochrome P450-mediated herb-drug interaction (HDI) of Polygonum multiflorum Thunb. based on pharmacokinetic studies and in vitro inhibition assays. Phytomedicine 2023;112:154710. 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

Fo-ti Also Interacts With Other Medications

Fo-ti has 1,256 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 Fo-ti

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

Everything else you take

See Every Supplement That Interacts With Benzhydrocodone, Acetaminophen

This page covers Fo-ti 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 Fo-ti as Part of a Dietary Supplement Product? Check It for Interactions

We hold 976 real supplement products containing Fo-ti, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Fo-ti. Your product may carry other ingredients that interact with Benzhydrocodone, Acetaminophen too, on top of Fo-ti — 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 Fo-ti 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 Fo-ti
Top 25%

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

29 days ago today
Medication Benzhydrocodone, Acetaminophen
Steady interest

#2,169 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 Fo-ti

What is Fo-ti?

  • Anti-aging and longevity
  • Hair graying and hair loss
  • General tonic for vitality
  • Constipation
  • High cholesterol

Fo-ti (He Shou Wu) is a root used in traditional Chinese medicine, often promoted for healthy aging and hair. High-quality human evidence for these benefits is limited, and processed Fo-ti has been linked to reports of liver injury, so caution and professional guidance are important.

Read the full Fo-ti 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 & Fo-ti

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

0Major
1,256Moderate
0Minor
1,573No known interaction
Moderate

1,256 interactions

Showing 60 of 1,256 moderate interactions — see all 1,256 on the Fo-ti page.

No interaction 1,573 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

Keep exploring
Pharmacist Counseling Corner

Taking Fo-ti and Benzhydrocodone, Acetaminophen Together: Common Questions

Can you take Fo-ti 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 Fo-ti and Benzhydrocodone, Acetaminophen?
Benzhydrocodone, Acetaminophen belongs to more than one drug category, and Fo-ti 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 Fo-ti 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.