Drug & supplement interaction

L-arginine + Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen brand name: Combogesic.

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

L-arginine has a moderate interaction with Acetaminophen, Ibuprofen. Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.

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

L-arginine and Acetaminophen, Ibuprofen

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

Why this applies to Acetaminophen, Ibuprofen

Acetaminophen, Ibuprofen falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group L-arginine interacts with.

Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.
Preliminary research suggests that L-arginine infusions reduce platelet aggregation in humans. The clinical significance of this effect is unclear.
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 for Combogesic, which combines acetaminophen and ibuprofen. The ibuprofen half already nudges your platelets to be a little less sticky, so they don't clump together as easily. L-arginine may do something similar on its own, since some early studies hint it can lower platelet activity. Put them together and, in theory, you could bruise more easily or bleed a touch longer than usual.

I want to be honest about how soft this evidence is. It's based on pharmacology and small infusion studies, not real-world cases, so for most healthy folks the risk is low. Still, if you take blood thinners, have a bleeding condition, or use ibuprofen regularly, run this combo past your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Sozykin, A. V., Noeva, E. A., Balakhonova, T. V., Pogorelova, O. A., and Men'shikov, M. I. [Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris]. Ter.Arkh. 2000;72(8):24-27.
  2. Saleh, A. I., Abdel Maksoud, S. M., El-Maraghy, S. A., and Gad, M. Z. Protective effect of L-arginine in experimentally induced myocardial ischemia: comparison with aspirin. J Cardiovasc.Pharmacol.Ther 2011;16(1):53-62. PubMed
  3. Adams, M. R., Forsyth, C. J., Jessup, W., Robinson, J., and Celermajer, D. S. Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. J Am Coll.Cardiol 1995;26(4):1054-1061. PubMed
  4. Bode-Boger, S. M., Boger, R. H., Creutzig, A., Tsikas, D., Gutzki, F. M., Alexander, K., and Frolich, J. C. L-arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy subjects. Clin.Sci.(Lond) 1994;87(3):303
  5. Marfella, R., Acampora, R., Verrazzo, G., Ziccardi, P., De, Rosa N., Giunta, R., and Giugliano, D. Metformin improves hemodynamic and rheological responses to L-arginine in NIDDM patients. Diabetes Care 1996;19(9):934-939. PubMed
  6. Giugliano, D., Marfella, R., Verrazzo, G., Acampora, R., Coppola, L., Cozzolino, D., and D'Onofrio, F. The vascular effects of L-Arginine in humans. The role of endogenous insulin. J Clin.Invest 2-1-1997;99(3):433-438. PubMed
  7. Wolf, A., Zalpour, C., Theilmeier, G., Wang, B. Y., Ma, A., Anderson, B., Tsao, P. S., and Cooke, J. P. Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. J Am Coll.Cardiol 3-1-1997;29(3):479-485. PubMed
  8. Marietta, M., Facchinetti, F., Neri, I., Piccinini, F., Volpe, A., and Torelli, G. L-arginine infusion decreases platelet aggregation through an intraplatelet nitric oxide release. Thromb.Res 10-15-1997;88(2):229-235. 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

L-arginine Also Interacts With Other Medications

L-arginine has 394 moderate, 8 minor known drug interactions in our database — the Acetaminophen, Ibuprofen one above is one of them. If you take anything else, check it against the full list below.

Moderate 394 Minor 8 No known interaction 2,428 (incl. Acetaminophen, Ibuprofen)
Taking anything else?

Check Another of Your Medications Against L-arginine

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

From our Q&A

Questions About L-arginine or Acetaminophen, Ibuprofen

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers L-arginine or Acetaminophen, Ibuprofen, 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, Ibuprofen

This page covers L-arginine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Ibuprofen page lists 342 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 · 290 moderate · 45 minor.

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

“Combogesic pairs acetaminophen with ibuprofen, so it inherits the vulnerabilities of both drugs, and its supplement list deserves real attention before you add anything to it. Of the 342 ingredients on file, 7 carry a major rating, and those are the ones to understand first.”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Ibuprofen interaction page

One more smart check

Taking L-arginine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 26 real supplement products containing L-arginine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides L-arginine. Your product may carry other ingredients that interact with Acetaminophen, Ibuprofen too, on top of L-arginine — 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 L-arginine and Acetaminophen, Ibuprofen 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 L-arginine
Steady interest

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

29 days ago today
Medication Acetaminophen, Ibuprofen
Top 25%

#421 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 L-arginine

What is L-arginine?

L-arginine
  • High blood pressure
  • Erectile dysfunction
  • Athletic performance
  • Chest pain (angina)
  • Improving blood flow

L-arginine is an amino acid that the body uses to make nitric oxide, a substance that helps blood vessels relax and widen. It is popularly used for blood pressure, erectile dysfunction, and exercise, but the evidence is mixed and stronger for some uses than others. It is generally well tolerated in healthy adults, but talk with a pharmacist or doctor before using it, especially if you have heart problems or take other medicines.

Read the full L-arginine monograph & all interactions
Keep checking

Other Drugs & L-arginine

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

0Major
394Moderate
8Minor
2,427No known interaction
394 Moderate 8 Minor 2,427 No interaction
Moderate

394 interactions

Showing 60 of 394 moderate interactions — see all 394 on the L-arginine page.

Minor

8 interactions

No interaction 2,427 drugs checked — show the list

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

Showing the 60 most looked-up of 2,427 medications checked with no known interaction — see the full L-arginine list.

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

Can you take L-arginine with Acetaminophen, Ibuprofen?
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.
How serious is the L-arginine and Acetaminophen, Ibuprofen 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, Ibuprofen and L-arginine?

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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.