Drug & supplement interaction

Niacin + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

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

Niacin has a moderate interaction with Acetaminophen, Butalbital, Codeine Phosphate. Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.

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

Niacin and Acetaminophen, Butalbital, Codeine Phosphate

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

Moderate

HEPATOTOXIC DRUGS

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate falls under HEPATOTOXIC DRUGS — the group Niacin interacts with.

Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
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.
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 thing to know about pairing high-dose niacin with this combo pill (Phrenilin with codeine). One of its ingredients, acetaminophen, is processed by the liver and, in large amounts or with heavy alcohol use, it can stress the liver. Niacin in big, drug-like doses (especially the sustained-release kind) has also been linked to liver irritation. So the concern is simple: two things that can each tax the liver, working at the same time.

To be fair, this is a theoretical worry based on how these substances behave, not proven harm from taking them together. The everyday vitamin B3 amount in a multivitamin is very unlikely to matter. If you take high-dose niacin, just check with your pharmacist or doctor first so your liver stays safe.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. Bays HE, Dujovne CA. Drug interactions of lipid-altering drugs. Drug Saf 1998;19:355-71. PubMed
  3. Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81. PubMed
  4. 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
  5. 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
  6. 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
  7. Bassan M. A case for immediate-release niacin. Heart Lung. 2012 Jan-Feb;41(1):95-8. PubMed
  8. 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

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 726 moderate known drug interactions in our database — the Acetaminophen, Butalbital, Codeine Phosphate one above is one of them. If you take anything else, check it against the full list below.

Moderate 726 No known interaction 2,104 (incl. Acetaminophen, Butalbital, Codeine Phosphate)
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 Acetaminophen, Butalbital, Codeine Phosphate

This page covers Niacin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

Open the Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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 Acetaminophen, Butalbital, Codeine Phosphate 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%

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,517 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
726Moderate
0Minor
2,103No known interaction
726 Moderate 2,103 No interaction
Moderate

726 interactions

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.

Showing the 60 most looked-up of 2,103 medications checked with no known interaction — see the full Niacin list.

See the full Niacin interactions page
See every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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 Acetaminophen, Butalbital, Codeine Phosphate supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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 Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Niacin with Acetaminophen, Butalbital, Codeine Phosphate?
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 Niacin and Acetaminophen, Butalbital, Codeine Phosphate 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, Butalbital, Codeine Phosphate 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.