Carbamazepine and Acetaminophen And Codeine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Carbamazepine
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.
Your pain medicine contains acetaminophen (Tylenol) plus codeine, and you also take carbamazepine for seizures or mood. Carbamazepine speeds up your liver, so it makes your body break down acetaminophen faster. That does two things: you may get a bit less pain and fever relief from the acetaminophen, and your liver makes more of a byproduct that can be hard on it, especially with high or frequent doses.
The good news is this is manageable. Please don't change anything on your own. Your care team can keep an eye on things and adjust your acetaminophen dose if needed. Never take extra acetaminophen (including in cold or sleep products) to make up for weaker relief. Talk to your pharmacist or doctor first.
Effect: Carbamazepine, a potent enzyme inducer (CYP450, including CYP2E1/3A pathways), increases acetaminophen metabolism, lowering parent-drug exposure/bioavailability while increasing formation of the hepatotoxic metabolite NAPQI.
- Direction: Reduced analgesic/antipyretic effect plus increased hepatotoxicity risk, greatest with high, frequent, or overdose acetaminophen exposure.
- Onset: Delayed. Evidence: Probable; enzyme-induced patients recover worse from acetaminophen overdose.
- Note: The codeine component is a CYP2D6 prodrug and is not the focus here.
- Management: Avoid high/chronic acetaminophen dosing; use lowest effective dose. Monitor hepatic function and clinical response; individualize acetaminophen dose.
What happens
An increased risk of acetaminophen hepatotoxicity and reduced acetaminophen exposure
Interaction Deep Dive
Coadministration of carBAMazepine and acetaminophen may result in reduced acetaminophen exposure. If coadministering, closely monitor acetaminophen levels and adjust the acetaminophen dosage as needed54. The hepatotoxicity of acetaminophen may be related to the formation of toxic metabolites in the liver. When carBAMazepine, an enzyme inducer, is given concurrently with high and frequent doses of acetaminophen, the induction of the metabolism of acetaminophen may result in an increased level of hepatotoxic metabolites. In support of this theory, it has been observed that patients who receive enzyme-inducing agents do not recover as well from an acetaminophen overdose as patients who are not taking enzyme-inducing drugs. The significance of this interaction at therapeutic doses of acetaminophen administered intermittently appears low. In addition, acetaminophen has been shown to have lower bioavailability in epileptic patients receiving enzyme-inducing agents 6.
Why it happens (mechanism)
Increased metabolism of acetaminophen resulting in abnormally high levels of hepatotoxic metabolites; unknown
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise.
- Watch total acetaminophen: Avoid extra acetaminophen from over-the-counter cold, flu, or sleep products, since your risk is highest with high or frequent doses.
- Dosing: Your acetaminophen dose may need to be adjusted and individualized by your care team, and they may monitor you more closely.
- Speak up: Tell your pharmacist or doctor if your pain or fever isn't controlled, or if you notice yellowing skin/eyes, dark urine, nausea, or right-upper-belly pain.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A 17-year-old female with a history of anorexia nervosa who was taking carBAMazepine 300 mg daily for mood stabilization consumed acetaminophen 7800 mg in a suicide attempt. When she was admitted to the hospital, her liver function tests were markedly elevated and her serum acetaminophen concentration was 15 mcg/mL. Acetylcysteine treatment was started and her acetaminophen level fell as anticipated. Nevertheless, eight days afterward she received a liver transplant because of fulminant hepatic failure that was thought to result from a combination of low body weight, malnutrition, and carBAMazepine therapy. A small fraction of acetaminophen is metabolized by the cytochrome P450 system into toxic metabolites, which are subsequently detoxified by glutathione. CarBAMazepine is recognized to induce the cytochrome P450 system, and her malnourished state depleted her glutathione concentrations. These two factors led to a higher concentration of toxic acetaminophen metabolites, causing liver failure 7.
Common questions
Can I take Carbamazepine and Acetaminophen And Codeine together?
Carbamazepine speeds up acetaminophen breakdown, weakening its pain relief and raising the risk of liver-damaging byproducts at high or frequent doses. Use the lowest effective acetaminophen dose, avoid stacking other acetaminophen products, and let your care team monitor and adjust. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Carbamazepine and Acetaminophen And Codeine 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 is the Carbamazepine and Acetaminophen And Codeine interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Watch total acetaminophen: Avoid extra acetaminophen from over-the-counter cold, flu, or sleep products, since your risk is highest with high or frequent doses. Dosing: Your acetaminophen dose may need to be adjusted and individualized by your care team, and they may monitor you more closely. Speak up: Tell… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Carbamazepine or Acetaminophen And Codeine 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 (7)
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: CARBATROL(R) oral extended-release capsules, carbamazepine oral extended-release capsules. Takeda Pharmaceuticals America Inc (per FDA), Lexington, MA, 2023. DailyMed
- Product Information: Tegretol(R) oral chewable tablets, oral tablets, oral suspension, carbamazepine oral chewable tablets, oral tablets, oral suspension. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Product Information: Tegretol(R)-XR oral extended-release tablets, carbamazepine oral extended-release tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023. DailyMed
- Perucca E & Richens A: Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs. Br J Clin Pharmacol 1979; 7:201-206. PubMed
- Young CR & Mazure CM: Fulminant hepatic failure from acetaminophen in an anorexic patient treated with carbamazepine (letter). J Clin Psychiatry 1998; 59:622. PubMed
Keep reading about Acetaminophen And Codeine
Keep reading about Carbamazepine
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