Carbamazepine with Acetaminophen Interaction Details
Brand Names Associated with Carbamazepine
- Carbamazepine
- Carbatrol®
- Epitol®
- Equetro®
- Tegretol®
- Tegretol®-XR
- Teril®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 25, 2024
Interaction Effect
An increased risk of acetaminophen hepatotoxicity and reduced acetaminophen exposure
Interaction Summary
Coadministration of carBAMazepine and acetaminophen may result in reduced acetaminophen exposure. If coadministering, closely monitor acetaminophen levels and adjust the acetaminophen dosage as needed[1][2]. 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 [3].
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Coadministration of carBAMazepine and acetaminophen may result in reduced acetaminophen exposure. If coadministering, closely monitor acetaminophen levels and adjust the acetaminophen dosage as needed[1][2]. 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 [3].
Mechanism Of Interaction
Increased metabolism of acetaminophen resulting in abnormally high levels of hepatotoxic metabolites; unknown
Literature Reports
A) A 17-year-old female with a history of anorexia nervosa and who was receiving carBAMazepine 300 mg daily for mood stabilization ingested acetaminophen 7800 mg in a suicide attempt. Upon admission to the hospital, her liver function tests were significantly elevated and her serum acetaminophen level was 15 mcg/mL. Treatment with acetylcysteine was initiated and her acetaminophen level decreased in the expected manner. However, eight days later, she underwent a liver transplant because of fulminant hepatic failure that was believed to be due to a combination of low body weight, malnutrition, and carBAMazepine therapy. A small portion of acetaminophen is metabolized by the cytochrome P450 system to toxic metabolites which are then detoxified by glutathione. CarBAMazepine is known to induce the cytochrome P450 system, and her malnutrition status depleted her glutathione concentrations. These two factors resulted in a greater concentration of acetaminophen toxic metabolites, resulting in liver failure [4].
References
1 ) Product Information: Tegretol(R)-XR oral extended-release tablets, carbamazepine oral extended-release tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2023.
2 ) 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.
3 ) Perucca E & Richens A: Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs. Br J Clin Pharmacol 1979; 7:201-206.
4 ) Young CR & Mazure CM: Fulminant hepatic failure from acetaminophen in an anorexic patient treated with carbamazepine (letter). J Clin Psychiatry 1998; 59:622.
Carbamazepine Overview
-
Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.