Drug & supplement interaction

Niacin + Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine brand names: Norgesic Forte, Invagesic, Invagesic Forte, Orphengesic, Norgesic, and others.

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

Aspirin, Caffeine, Orphenadrine falls into 2 drug categories that Niacin can interact with; the most serious is rated moderate. Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.

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

Niacin and Aspirin, Caffeine, Orphenadrine

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

Why Are There 2 Interactions?

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

Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

1 of 2

Why this applies to Aspirin, Caffeine, Orphenadrine

Aspirin, Caffeine, Orphenadrine falls under ANTICOAGULANT/ANTIPLATELET DRUGS — the group Niacin interacts with.

Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.
Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin. Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin.
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

The piece of this combo pill that matters here is the aspirin, which thins the blood a bit by making platelets less sticky. The thinking is that high-dose niacin might add to that effect. A few reports have also tied sustained-release niacin to lower clotting factors and even drops in platelet counts. Put together, you could in theory bruise or bleed a little more easily, see nosebleeds, or notice bleeding gums.

To be honest, this is a theoretical concern based mostly on how these work, not on strong studies. Everyday vitamin amounts of niacin are very unlikely to cause trouble. The caution really applies to large, drug-like niacin doses. Before starting one of those, please check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Dearing BD, Lavie CJ, Lohmann TP, Genton E. Niacin-induced clotting factor synthesis deficiency with coagulopathy. Arch Intern Med. 1992;152(4):861-3. DOI
  2. O'Brien T, Silverberg JD, Nguyen TT. Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin. Mayo Clin Proc. 1992;67(5):465-8. PubMed
Minor

ASPIRIN

2 of 2
Large doses of aspirin might alter the clearance of niacin.
Aspirin is often used with niacin to reduce niacin-induced flushing. Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal. Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45%. This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg.
Severity Minor Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

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

Here's the gist for your combination product (which contains aspirin, caffeine, and orphenadrine). The interaction on file is between the aspirin piece and niacin. Aspirin and niacin both get cleared using a similar pathway in the body, so large aspirin doses can slow how fast niacin leaves your system. At a high aspirin dose like 1 gram, niacin clearance dropped by about 45 percent, but at the smaller doses found in most aspirin products this effect is considered minor and usually not meaningful.

In practice, people sometimes take a little aspirin on purpose to ease the warm, red, tingly flushing that high-dose niacin can cause. If you take prescription-strength niacin, it's worth a quick chat with your pharmacist to make sure the combo is right for you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32. PubMed
  2. Whelan AM, Price SO, Fowler SF, Hainer BL. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract 1992;34:165-8.
  3. Jungnickel PW, Maloley PA, Vander Tuin EL, et al. Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions. J Gen Intern Med 1997;12:591-6. PubMed
  4. Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71. PubMed
  5. Ding RW, Kolbe K, Merz B, et al. Pharmacokinetics of nicotinic acid-salicylic acid interaction. Clin Pharmacol Ther 1989;46:642-7. 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

Niacin Also Interacts With Other Medications

Niacin has 728 moderate known drug interactions in our database — the Aspirin, Caffeine, Orphenadrine one above is among them. If you take anything else, check it against the full list below.

Moderate 728 No known interaction 2,102 (incl. Aspirin, Caffeine, Orphenadrine)
Taking anything else?

Check Another of Your Medications Against Niacin

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Caffeine, Orphenadrine

This page covers Niacin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Caffeine, Orphenadrine page lists 350 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: 14 major · 289 moderate · 47 minor.

From our pharmacist’s overview on the Aspirin, Caffeine, Orphenadrine page

“Aspirin, caffeine, and orphenadrine (the Norgesic and Orphengesic brands) come with a supplement list that deserves real vigilance, with 14 of its 350 entries rated major. Over 200 of those ingredients can add to aspirin's effect on platelets and raise bleeding risk, another 44 stack stimulant effects on top of the caffeine, and grapef…”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Caffeine, Orphenadrine interaction page

One more smart check

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

We hold 933 real supplement products containing Niacin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Niacin. Your product may carry other ingredients that interact with Aspirin, Caffeine, Orphenadrine too, on top of Niacin — 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 Niacin and Aspirin, Caffeine, Orphenadrine 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 Niacin
Top 25%

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

29 days ago today
Medication Aspirin, Caffeine, Orphenadrine
Top 5%

#94 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 Niacin

What is Niacin?

Niacin
  • High cholesterol
  • Vitamin B3 deficiency (pellagra)
  • Heart health support
  • General energy and metabolism

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescription-strength niacin has been used to adjust cholesterol levels, but high doses can cause flushing and other side effects and should only be taken under medical supervision. Always talk with a pharmacist or doctor before using high-dose niacin supplements.

Read the full Niacin monograph & all interactions
Keep checking

Other Drugs & Niacin

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

0Major
728Moderate
0Minor
2,101No known interaction
728 Moderate 2,101 No interaction
Moderate

728 interactions

Showing 60 of 728 moderate interactions — see all 728 on the Niacin page.

No interaction 2,101 drugs checked — show the list

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

Showing the 60 most looked-up of 2,101 medications checked with no known interaction — see the full Niacin list.

See the full Niacin interactions page
See every supplement checked against Aspirin, Caffeine, Orphenadrine, 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
Niacin monograph › Uses, safety, and every drug interaction in one place Aspirin, Caffeine, Orphenadrine supplement interactions › Every supplement checked against Aspirin, Caffeine, Orphenadrine, 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 Niacin and Aspirin, Caffeine, Orphenadrine Together: Common Questions

Can you take Niacin with Aspirin, Caffeine, Orphenadrine?
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 Niacin and Aspirin, Caffeine, Orphenadrine?
Aspirin, Caffeine, Orphenadrine belongs to more than one drug category, and Niacin 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 Niacin and Aspirin, Caffeine, Orphenadrine 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 Aspirin, Caffeine, Orphenadrine and Niacin?

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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.