Drug & supplement interaction

Grape + Acetaminophen, Hydrocodone

Acetaminophen, Hydrocodone brand names: Vicodin, Vicodin ES, Vicodin HP, Lortab, Norco 10/325, and others.

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

Acetaminophen, Hydrocodone falls into 4 drug categories that Grape can interact with; the most serious is rated moderate. Theoretically, grape juice might reduce the levels of CYP1A2 substrates.

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

Grape and Acetaminophen, Hydrocodone

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

Why Are There 4 Interactions?

Grape interacts with whole categories of medication. Acetaminophen, Hydrocodone falls into 4 of those categories, so it can interact with Grape 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 1A2 (CYP1A2) SUBSTRATES

1 of 4

Why this applies to Acetaminophen, Hydrocodone

Acetaminophen, Hydrocodone falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Grape interacts with.

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.
Severity Moderate Likelihood Possible Evidence B

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 gist for your Norco or Vicodin (the acetaminophen plus hydrocodone combo). The concern on file is that grape juice may speed up an enzyme called CYP1A2, which could lower blood levels of medicines that enzyme handles. If that happened, you might notice your pain relief feeling a bit weaker than usual.

Honestly, though, I wouldn't lose sleep over this one. The evidence is thin and theoretical, based on a small study using a different drug. Hydrocodone is mainly processed by other enzymes (CYP2D6 and CYP3A4), not CYP1A2, so a glass of grape juice or some grapes is very unlikely to change how well your medication works. If you're using concentrated grape supplements daily, just mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40. PubMed
Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

2 of 4

Acetaminophen, Hydrocodone also falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES.

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. 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 this one. The hydrocodone in your Vicodin or Norco is a prodrug, meaning your liver uses an enzyme called CYP2D6 to convert part of it into hydromorphone, the form that delivers a good chunk of the pain relief. Lab studies suggest grape seed extract might slow that same enzyme down. If that happened in real life, less hydrocodone would be turned on, so you could get weaker pain control than expected.

Now, the honest part: this has only been seen in test tubes, never in actual people, so I wouldn't lose sleep over it. Eating grapes is no concern at all. If you're using a concentrated grape seed extract supplement, just mention it to your pharmacist or doctor so they can keep an eye on whether your pain medicine is still working well.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 4

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

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have 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: the hydrocodone part of Vicodin or Norco relies on liver enzymes (including CYP3A4) to be processed. Grape seed extract might nudge that enzyme, but the research is genuinely mixed. Some lab studies hint it slows the enzyme down, while animal studies suggest it may speed it up. We really don't know which way it goes in people, and honestly, no such problem has actually been reported in humans.

In theory, if it slowed the enzyme, you could feel a bit more drowsiness, dizziness, or constipation from the hydrocodone. If it sped things up, your pain relief might feel weaker. Both are unproven and based only on test-tube and animal work. Eating grapes is no concern. If you take a concentrated grape seed supplement, just give your pharmacist a heads-up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  2. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

4 of 4

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

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. 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 gist with Norco or Vicodin (that's acetaminophen plus hydrocodone) and grape seed supplements. Lab and animal studies hint that grape seed extract may slow down an enzyme called CYP2E1. For acetaminophen, that enzyme actually helps create a small amount of a toxic byproduct, so in theory, blocking it a bit could mean less stress on the liver, not more. This isn't a case where your pain meds would suddenly hit harder.

The honest truth is this interaction has only been seen in test tubes and animals, never in real people, so I wouldn't lose sleep over it. Eating grapes certainly won't be an issue. If you're thinking about a concentrated grape seed supplement while on this combo, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Ray, S. D., Parikh, H., Hickey, E., Bagchi, M., and Bagchi, D. Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation. Mol Cell B 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

Grape Also Interacts With Other Medications

Grape has 867 moderate, 42 minor known drug interactions in our database — the Acetaminophen, Hydrocodone one above is among them. If you take anything else, check it against the full list below.

Moderate 867 Minor 42 No known interaction 1,921 (incl. Acetaminophen, Hydrocodone)
Taking anything else?

Check Another of Your Medications Against Grape

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

From our Q&A

Questions About Grape or Acetaminophen, Hydrocodone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grape or Acetaminophen, Hydrocodone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Hydrocodone

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Hydrocodone page lists 270 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: 11 major · 215 moderate · 44 minor.

From our pharmacist’s overview on the Acetaminophen, Hydrocodone page

“Someone taking hydrocodone with acetaminophen (Vicodin, Norco) for post-surgical or dental pain often reaches for a sleep aid, kava, or a glass of wine at night, and that is exactly where the risk sits. This combination calls for genuine vigilance.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Hydrocodone interaction page

One more smart check

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

We hold 8,053 real supplement products containing Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grape. Your product may carry other ingredients that interact with Acetaminophen, Hydrocodone too, on top of Grape — 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 Grape and Acetaminophen, Hydrocodone 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 Grape
Top 5%

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

29 days ago today
Medication Acetaminophen, Hydrocodone
Top half

#1,407 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 Grape

What is Grape?

Grape
  • Antioxidant support
  • Heart and circulation health
  • Vein problems (such as varicose veins)
  • Eye health
  • General anti-inflammatory support

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is healthy and generally safe, the supplement evidence for treating specific conditions is mostly limited or preliminary. Talk with your pharmacist or doctor before starting a grape supplement.

Read the full Grape monograph & all interactions
Keep checking

Other Drugs & Grape

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

0Major
867Moderate
42Minor
1,920No known interaction
867 Moderate 42 Minor 1,920 No interaction
Moderate

867 interactions

Showing 60 of 867 moderate interactions — see all 867 on the Grape page.

Minor

42 interactions

No interaction 1,920 drugs checked — show the list

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

Showing the 60 most looked-up of 1,920 medications checked with no known interaction — see the full Grape list.

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

Can you take Grape with Acetaminophen, Hydrocodone?
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 Grape and Acetaminophen, Hydrocodone?
Acetaminophen, Hydrocodone belongs to more than one drug category, and Grape 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 Grape and Acetaminophen, Hydrocodone 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 Acetaminophen, Hydrocodone and Grape?

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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.