Drug & supplement interaction

Grape + Aspirin, Chlorpheniramine, Phenylpropanolamine

Aspirin, Chlorpheniramine, Phenylpropanolamine brand name: Alka-Seltzer Plus Cold.

Moderate Interaction
The bottom line Moderate

Aspirin, Chlorpheniramine, Phenylpropanolamine falls into 2 drug categories that Grape can interact with; the most serious is rated moderate. It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.

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

Grape and Aspirin, Chlorpheniramine, Phenylpropanolamine

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Aspirin, Chlorpheniramine, Phenylpropanolamine

Aspirin, Chlorpheniramine, Phenylpropanolamine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Grape interacts with.

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 with grape seed extract and a combo product like Alka-Seltzer Plus Cold (which mixes aspirin, the antihistamine chlorpheniramine, and the decongestant phenylpropanolamine). The concern is that grape seed extract may nudge a liver enzyme called CYP3A4, which helps process some of these ingredients. The catch is the research is genuinely mixed: lab studies hint it might slow that enzyme, while animal studies suggest it could speed it up. None of this is a prodrug situation, so there's no flip to worry about.

The big thing to know is that this has never actually been reported in people, and the evidence is only test-tube and animal data. Eating grapes is no concern. If you take a concentrated grape seed supplement, just mention it to your pharmacist before pairing them.

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

ANTICOAGULANT/ANTIPLATELET DRUGS

2 of 2

Aspirin, Chlorpheniramine, Phenylpropanolamine 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

This combination cold product contains aspirin, which already thins the blood by keeping platelets from clumping together. Grape extracts, especially concentrated grape seed supplements, may have a mild blood-thinning effect of their own in lab studies. So in theory, pairing the two could add up and slightly raise your chance of bleeding or bruising, things like easy bruising, nosebleeds, or a cut that takes longer to stop.

I want to be honest about the evidence here: this is based on test-tube research, not real-world patient studies, so the actual risk for most people is probably small. Eating grapes or drinking a little grape juice is very unlikely to matter. Before adding a concentrated grape supplement, just run it by your pharmacist or doctor, especially if you bleed or bruise easily.

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

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 Aspirin, Chlorpheniramine, Phenylpropanolamine 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 Aspirin, Chlorpheniramine, Phenylpropanolamine

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 Aspirin, Chlorpheniramine, Phenylpropanolamine, 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 Aspirin, Chlorpheniramine, Phenylpropanolamine

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Chlorpheniramine, Phenylpropanolamine page lists 372 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 Ephedra (major).

By severity: 16 major · 308 moderate · 48 minor.

Open the Aspirin, Chlorpheniramine, Phenylpropanolamine 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 Aspirin, Chlorpheniramine, Phenylpropanolamine 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 Aspirin, Chlorpheniramine, Phenylpropanolamine 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%

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

29 days ago today
Medication Aspirin, Chlorpheniramine, Phenylpropanolamine
Steady interest

#1,680 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
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 Aspirin, Chlorpheniramine, Phenylpropanolamine Together: Common Questions

Can you take Grape with Aspirin, Chlorpheniramine, Phenylpropanolamine?
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 Grape and Aspirin, Chlorpheniramine, Phenylpropanolamine?
Aspirin, Chlorpheniramine, Phenylpropanolamine 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 Aspirin, Chlorpheniramine, Phenylpropanolamine 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.