Drug & supplement interaction

Grape + Naproxen

Naproxen brand names: Naprosyn, Naprelan, Anaprox, Anaprox DS, Naproxyn, and others.

Moderate Interaction
The bottom line Moderate

Naproxen falls into 3 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
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Interaction report

Grape and Naproxen

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Grape interacts with whole categories of medication. Naproxen falls into 3 of those categories, so it can interact with Grape in 3 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 3

Why this applies to Naproxen

Naproxen 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 grape and naproxen. Some of naproxen's breakdown happens through a liver enzyme called CYP1A2. There's a small study suggesting that grape juice may actually speed up that enzyme a bit. If that holds true, your body could clear naproxen slightly faster, which in theory might make it a touch less effective at easing your pain, swelling, or stiffness.

I want to be honest with you though: this is mostly theoretical and based on weak, early research using a different drug. For most people, drinking grape juice or eating grapes alongside naproxen isn't likely to cause a noticeable problem. If your naproxen ever seems to stop working as well, that's worth mentioning to your pharmacist or doctor.

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

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 3

Naproxen also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.
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 naproxen and grape supplements. Naproxen is an anti-inflammatory pain reliever (an NSAID), and one thing it already does is make platelets a little less sticky, which is part of why it can raise the chance of bruising, stomach irritation, or bleeding. Concentrated grape products, like grape seed extract, may have their own mild blood-thinning effect in lab studies. Stack the two and, in theory, that bleeding risk could nudge upward.

I want to be honest about how thin this evidence is. This concern comes from test-tube research, not real-world cases, so it's more of a caution than a proven problem. Eating grapes or drinking a little grape juice is very unlikely to matter. If you take a concentrated grape supplement, just run it by your pharmacist or doctor first, and watch for unusual bruising or stomach upset.

References
  1. de Lange, D. W., Scholman, W. L., Kraaijenhagen, R. J., Akkerman, J. W., and van de Wiel, A. Alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood. Eur.J Clin.Invest 2004;34(12):818-824. PubMed
  2. de Lange, D. W., Verhoef, S., Gorter, G., Kraaijenhagen, R. J., van de Wiel, A., and Akkerman, J. W. Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox. Alcohol Clin.Exp.Res 2007;31(8):1308-1314 PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Naproxen also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Your body relies on a liver enzyme called CYP2C9 to clear naproxen out of your system. The thought here is that compounds in grape juice or grape seed extract might slow that enzyme down a little. If that happened, naproxen could linger longer and its usual side effects, like stomach upset, heartburn, or a higher chance of stomach irritation, could be a touch more noticeable. Naproxen is an active drug (not a prodrug), so blocking that enzyme would tend to nudge its effects up, not down.

Here's the reassuring part: this is mostly lab-dish data, and the human research actually conflicts. In one small study, a glass of grape juice didn't change how people cleared a similar drug. Bottom line: enjoying grapes or grape juice is very unlikely to be a problem, but check with your pharmacist before starting a concentrated grape seed supplement.

References
  1. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  2. 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
  3. 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

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 Naproxen 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 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 Naproxen

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 Naproxen, 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 Naproxen

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Naproxen page lists 311 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Piracetam (major).

By severity: 7 major · 260 moderate · 44 minor.

Open the Naproxen 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 Naproxen 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 Naproxen 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 Naproxen
Top 5%

#55 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
Medication

About Naproxen

What Is Naproxen Used For?

Brand names: Naprosyn, Naprelan, Anaprox, Anaprox DS, Naproxyn, Navalbine, Naproxen, Naprosyn EC, Napro-Na, Aleve, Arthroxen, Synflex, EC-Naprosyn

Naproxen tablets, naproxen sodium tablets, and naproxen oral suspension are used to relieve the signs and symptoms of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis. They are also used for tendonitis, bursitis, and acute gout, and for managing pain and primary dysmenorrhea (menstrual cramps).

Naproxen Sodium Controlled-Release Tablets are indicated for the same conditions plus the relief of mild to moderate pain. Several over-the-counter naproxen sodium products are indicated for the temporary relief of minor aches and pains from headache, backache, muscular aches, toothache, menstrual cramps, minor arthritis pain, and the common cold, and to temporarily reduce fever.

See full Naproxen drug information
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
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
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 Grape and Naproxen Together: Common Questions

Can you take Grape with Naproxen?
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 3 interactions listed for Grape and Naproxen?
Naproxen 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 Naproxen 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 Naproxen and Grape?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.