Niacin + Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.
Acetaminophen, Aspirin, Caffeine falls into 3 drug categories that Niacin can interact with; the most serious is rated moderate. Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
Read the full interaction reportNiacin and Acetaminophen, Aspirin, Caffeine
These two interact in 3 distinct ways. Each one is explained separately below.
Why Are There 3 Interactions?
Niacin interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 3 of those categories, so it can interact with Niacin in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).
HEPATOTOXIC DRUGS
1 of 3Why this applies to Acetaminophen, Aspirin, Caffeine
Acetaminophen, Aspirin, Caffeine falls under HEPATOTOXIC DRUGS — the group Niacin interacts with.
Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses. Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin.
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.
Here's the gist with something like Excedrin Migraine (acetaminophen, aspirin, and caffeine) and niacin. The acetaminophen part of this combo is processed by your liver, and in higher doses it can be hard on liver cells. High, drug-like doses of niacin (especially sustained-release versions) have also been linked to liver irritation. So the worry is simply that two things that can stress the liver are stacking up at the same time.
I want to be honest: this is a theoretical concern based on how these work, not something proven to happen often. Everyday B3 from food or a basic multivitamin is very unlikely to be an issue. If you take high-dose niacin or use acetaminophen products regularly, please check in with your pharmacist or doctor first.
- American Society of Health-System Pharmacists. ASHP Therapeutic Position Statement on the safe use of niacin in the management of dyslipidemias. Am J Health Syst Pharm 1997;54:2815-9. DOI
- Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71. PubMed
- Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81. PubMed
- Etchason JA, Miller TD, Squires RW, et al. Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin. Mayo Clin Proc. 1991;66(1):23-8. PubMed
- Henkin Y, Johnson KC, Segrest JP. Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin. JAMA. 1990;264(2):241-3. DOI
- Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med. 1991;91(3):239-46. PubMed
- Bassan M. A case for immediate-release niacin. Heart Lung. 2012 Jan-Feb;41(1):95-8. PubMed
- Nawaz N, Mistretta T, Karime C, Lewis J, Wolf E. Cholestatic Drug-Induced Liver Injury in a Patient Taking High-Dose Niacin for Hyperlipidemia. J Investig Med High Impact Case Rep 2024;12:23247096231224349. PubMed
ANTICOAGULANT/ANTIPLATELET DRUGS
2 of 3Acetaminophen, Aspirin, Caffeine also falls under ANTICOAGULANT/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.
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.
Here's what matters with this combo: the aspirin in Excedrin already thins your blood a bit by making platelets less sticky. High-dose niacin, in rare reports, has been linked to lower clotting factors and reduced platelets. So in theory, stacking concentrated niacin on top of aspirin could nudge you toward easier bruising, nosebleeds, or bleeding that's slower to stop.
I want to be honest though, this is a theoretical concern based on how these work, not strong proof. The everyday niacin in a regular multivitamin or your food won't cause trouble. It's the big drug-strength niacin doses to watch. If you take high-dose niacin and use Excedrin often, just check in with your pharmacist or doctor first.
- 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
- 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
ASPIRIN
3 of 3Acetaminophen, Aspirin, Caffeine also falls under ASPIRIN.
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.
Well-controlled human studies have demonstrated the likely existence of this interaction.
Here's the good news: this combination is actually pretty friendly. Products like Excedrin contain aspirin, and aspirin is often used on purpose alongside niacin to calm the flushing (that warm, red, tingly feeling) that high-dose niacin can cause. So if anything, the aspirin in your Excedrin may help take the edge off niacin flushing.
The interaction on file simply notes that large doses of aspirin can slow how fast your body clears niacin. That matters mostly at gram-sized aspirin doses. The amount in a typical Excedrin tablet (around 250 mg of aspirin) is too small to meaningfully change niacin levels. I wouldn't lose sleep over this one, but if you take high-dose prescription niacin, check in with your pharmacist to be safe.
- Knodel LC, Talbert RL. Adverse effects of hypolipidaemic drugs. Med Toxicol 1987;2:10-32. PubMed
- Whelan AM, Price SO, Fowler SF, Hainer BL. The effect of aspirin on niacin-induced cutaneous reactions. J Fam Pract 1992;34:165-8.
- 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
- Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71. PubMed
- 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.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Niacin Also Interacts With Other Medications
Niacin has 726 moderate known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Niacin
We haven’t checked that one against Niacin yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Niacin. Pick one to open its full report.
See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine
This page covers Niacin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 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: 13 major · 312 moderate · 46 minor.
From our pharmacist’s overview on the Acetaminophen, Aspirin, Caffeine page
“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”
Reviewed by 2 · Jul 18, 2026
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 Acetaminophen, Aspirin, Caffeine 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:
Where Niacin and Acetaminophen, Aspirin, Caffeine 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.
#221 of 1,452 supplements looked up here in the last 7 days
#72 of 2,830 medications looked up here in the last 7 days
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.
About Niacin
What is 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.
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.
No drugs match “”.
726 interactions
- Diclofenac Sodium ›
- Diltiazem ›
- Nifedipine ›
- Ibuprofen ›
- Aspirin ›
- Insulin (rdna) ›
- Naproxen ›
- Doxycycline ›
- Minocycline ›
- Propranolol ›
- Tetracycline ›
- Levothyroxine ›
- Amoxicillin ›
- Hydrochlorothiazide ›
- Testosterone ›
- Verapamil ›
- Fenofibrate ›
- Levonorgestrel ›
- Quinidine ›
- Cyclosporine ›
- Glyburide ›
- Insulin (pork) ›
- Methyltestosterone ›
- Ciprofloxacin ›
- Nicotine ›
- Phenytoin ›
- Allopurinol ›
- Carbamazepine ›
- Diclofenac Potassium ›
- Dipyridamole ›
- Hydralazine ›
- Insulin (human) ›
- Acetaminophen ›
- Conjugated Estrogens ›
- Ketoprofen ›
- Methotrexate ›
- Nitrofurantoin ›
- Ofloxacin ›
- Propoxyphene ›
- Rifampin ›
- Testosterone Undecanoate ›
- Trichlormethiazide ›
- Acarbose ›
- Bendroflumethiazide ›
- Bivalirudin ›
- Dapsone ›
- Doxycycline Hyclate ›
- Duloxetine ›
- Eltrombopag ›
- Insulin Glargine ›
- Interferon Alfa-2b ›
- Interferon Beta-1b ›
- Isoniazid ›
- Itraconazole ›
- Levofloxacin ›
- Levothyroxine Sodium ›
- Liotrix ›
- Lisinopril ›
- Metolazone ›
- Minoxidil ›
Showing 60 of 726 moderate interactions — see all 726 on the Niacin page.
No interaction 2,103 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.
- Methylphenidate ›
- Sertraline ›
- Ivermectin ›
- Escitalopram ›
- Abemaciclib ›
- Tadalafil ›
- Docusate ›
- Valacyclovir ›
- Methamphetamine ›
- Hydroxyurea ›
- Sumatriptan ›
- Prednisone ›
- Lisdexamfetamine ›
- Bupropion ›
- Amitriptyline ›
- Bendamustine ›
- Acyclovir ›
- Amphetamine ›
- Fluoxetine ›
- Isotretinoin ›
- Lamotrigine ›
- Pregabalin ›
- Azithromycin ›
- Gabapentin ›
- Dextroamphetamine ›
- Clonazepam ›
- Methylene Blue ›
- Omeprazole ›
- Quetiapine ›
- Letrozole ›
- Buspirone ›
- Citalopram ›
- Diazepam ›
- Cyclopentolate ›
- Cephalexin ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Roxithromycin ›
- Levetiracetam ›
- Ezetimibe ›
- Finasteride ›
- Pegunigalsidase Alfa-iwxj ›
- Mirtazapine ›
- Estrogen ›
- Dexmethylphenidate ›
- Daptomycin ›
- Phentermine, Topiramate ›
- Mitomycin ›
- Hexobarbitone ›
- Carbidopa, Levodopa ›
- Alprazolam ›
- Aripiprazole ›
- Factor 7a ›
- Bromocriptine ›
- Levodopa ›
- Finasteride, Tadalafil ›
- Hethylphenidate Hcl ›
- Venlafaxine ›
- Dextromethorphan ›
- Cefaclor ›
- Dutasteride ›
Showing the 60 most looked-up of 2,103 medications checked with no known interaction — see the full Niacin list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Acetaminophen, Aspirin, Caffeine Is Linked to Lower Levels of 5 Nutrients
Natural Medicines records Acetaminophen, Aspirin, Caffeine as a medicine that can lower these. This is not an interaction with Niacin — it is a separate effect of the medicine, and it is a reason some people are advised to supplement rather than to avoid one:
Read the full Acetaminophen, Aspirin, Caffeine nutrient depletion report ›
Niacin is itself a nutrient we track — see which medications may deplete NIACIN.
Depletion records come from the licensed Natural Medicines database. Do not start a supplement on the strength of this page — ask your pharmacist or doctor whether it applies to you.
Taking Niacin and Acetaminophen, Aspirin, Caffeine Together: Common Questions
Can you take Niacin with Acetaminophen, Aspirin, Caffeine?
Why are there 3 interactions listed for Niacin and Acetaminophen, Aspirin, Caffeine?
How serious is the Niacin and Acetaminophen, Aspirin, Caffeine interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
Still Have a Question About Acetaminophen, Aspirin, Caffeine 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.