Acetaminophen and Isoniazid: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Isoniazid
No brand names on recordAcetaminophen
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of hepatotoxicity
Interaction Deep Dive
Concomitant use of acetaminophen and isoniazid has led to hepatotoxicity in isolated cases456. Isoniazid may demonstrate biphasic effects on CYP2E1, initially inhibiting then inducing CYP2E1 activity 3. Variations in CYP2E1 activity with isoniazid therapy may also depend on a patient's genetic predisposition as a rapid or slow acetylator. Use caution with concomitant administration of acetaminophen and isoniazid as this may lead to induction of CYP2E1 and increased exposure to toxic acetaminophen metabolites 1. Due to differing genetic predisposition in acetylator status, variable effects of isoniazid on CYP2E1, the potential for increased formation of toxic acetaminophen metabolites, and the additive risk of hepatotoxicity, the use of acetaminophen in isoniazid-treated patients should be avoided or limited.
Why it happens (mechanism)
Initial inhibition of CYP2E1-mediated metabolism of acetaminophen by isoniazid; induction of CYP2E1-mediated metabolism of acetaminophen by isoniazid
Literature reports
3 reports — tap to read
a) Isoniazid may have variable effects on CYP2E1, as determined in a pharmacokinetic study in patients with tuberculosis (N=11). Following 14 days of isoniazid therapy, CYP2E1 activity was significantly reduced in 8 patients, by a median of 71.7%, while 3 patients demonstrated an increase in CYP2E1 activity, by a median of 176% 2.
b) In a group of slow-acetylator volunteers given isoniazid 300 mg daily for 7 days (N=10), administration of acetaminophen 500 mg led to reduced then increased production of acetaminophen metabolites. When acetaminophen was given on day 1 or 3 of isoniazid, reduced levels of acetaminophen thioether metabolites were observed compared with acetaminophen monotherapy. However, when acetaminophen was given on day 8 or 10, increased levels of acetaminophen thioether metabolites were observed, compared with monotherapy or coadministration on days 1 or 3. Isoniazid may bind with CYP2E1 to reduce enzyme activity via ligand stabilization, with a compensatory increase in CYP2E1 production. After time, and especially following withdrawal of isoniazid, the increased levels of free CYP2E1 increased the enzyme activity. Thus, the interaction may be biphasic, with an initial reduction in CYP2E1 activity and reduced production of toxic acetaminophen metabolites, followed by an increase in CYP2E1 activity and greater production of toxic acetaminophen metabolites 3.
c) One study reported the cases of 3 patients who experienced hepatotoxicity after self-medication with acetaminophen that was taken concurrently with antituberculosis agents including isoniazid and rifampin. Although clinical signs and symptoms varied among the 3 patients, all had greatly increased serum levels of hepatic enzymes. All signs and symptoms of hepatotoxicity resolved after discontinuation of all medications, and, when antituberculosis treatment was resumed, no further adverse effects were seen 4 .
Common questions
Can I take Acetaminophen and Isoniazid together?
An increased risk of hepatotoxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen and Isoniazid interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Acetaminophen or Isoniazid need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: isoniazid oral tablets, isoniazid oral tablets. West-ward Pharmaceutical Corp. (per DailyMed), Eatontown, NJ, 2011. DailyMed
- Walubo A, Coetsee C, Arti D, et al: The effect of isoniazid containing regimen on CYP2E1 during antituberculosis therapy. Res Commun Mol Pathol Pharmacol 2005; 117-118:137-151.
- Zand R, Nelson SD, Slattery JT, et al: Inhibition and induction of cytochrome P4502E1-catalyzed oxidation by isoniazid in humans. Clin Pharmacol Ther 1993; 54(2):142-149. PubMed
- Nolan CM, Sandblom RE, Thummel KE, et al: Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. Chest 1994; 105:408-411. DOI
- Murphy R, Swartz R, & Watkins PB: Severe acetaminophen toxicity in a patient receiving isoniazid. Ann Intern Med 1990; 113:799-802. PubMed
- Moulding TS, Redeker AG, & Kanel GC: Acetaminophen, isoniazid, and hepatic toxicity (letter). Ann Intern Med 1991; 114:431. DOI
Keep reading about Isoniazid
Keep reading about Acetaminophen
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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